Benefits of Heart Rate Slowing With Ivabradine in Patients With Systolic Heart Failure and Coronary Artery Disease.

PubMed

Borer, Jeffrey S; Deedwania, Prakash C; Kim, Jae B; Böhm, Michael

2016-12-15

Heart rate (HR) is a risk factor in patients with chronic systolic heart failure (HF) that, when reduced, provides outcome benefits. It is also a target for angina pectoris prevention and a risk marker in chronic coronary artery disease without HF. HR can be reduced by drugs; however, among those used clinically, only ivabradine reduces HR directly in the sinoatrial nodal cells without other known effects on the cardiovascular system. This review provides current information regarding the safety and efficacy of HR reduction with ivabradine in clinical studies involving >36,000 patients with chronic stable coronary artery disease and >6,500 patients with systolic HF. The largest trials, Morbidity-Mortality Evaluation of the I f Inhibitor Ivabradine in Patients With Coronary Disease and Left Ventricular Dysfunction and Study Assessing the Morbidity-Mortality Benefits of the I f Inhibitor Ivabradine in Patients With Coronary Artery Disease, showed no effect on outcomes. The Systolic Heart Failure Treatment With the I f Inhibitor Ivabradine Trial, a randomized controlled trial in >6,500 patients with HF, revealed marked and significant HR-mediated reduction in cardiovascular mortality or HF hospitalizations while improving quality of life and left ventricular mechanical function after treatment with ivabradine. The adverse effects of ivabradine predominantly included bradycardia and atrial fibrillation (both uncommon) and ocular flashing scotomata (phosphenes) but otherwise were similar to placebo. In conclusion, ivabradine improves outcomes in patients with systolic HF; rates of overall adverse events are similar to placebo. Copyright © 2016 Elsevier Inc. All rights reserved.

Effectiveness of Ivabradine in Treating Stable Angina Pectoris

PubMed Central

Ye, Liwen; Ke, Dazhi; Chen, Qingwei; Li, Guiqiong; Deng, Wei; Wu, Zhiqin

2016-01-01

Abstract Many studies show that ivabradine is effective for stable angina. This meta-analysis was performed to determine the effect of treatment duration and control group type on ivabradine efficacy in stable angina pectoris. Relevant articles in the English language in the PUBMED and EMBASE databases and related websites were identified by using the search terms “ivabradine,” “angina,” “randomized controlled trials,” and “Iva.” The final search date was November 2, 2015. Articles were included if they were published randomized controlled trials that related to ivabradine treatment of stable angina pectoris. Patients with stable angina pectoris were included. The patients were classified according to treatment duration (<3 vs ≥3 months) or type of control group (placebo vs beta-receptor blocker). Angina outcomes were heart rate at rest or peak, exercise duration, and time to angina onset. Seven articles were selected. There were 3747 patients: 2100 and 1647 were in the ivabradine and control groups, respectively. The ivabradine group had significantly longer exercise duration when they had been treated for at least 3 months, but not when treatment time was less than 3 months. Ivabradine significantly improved time to angina onset regardless of treatment duration. Control group type did not influence the effect of exercise duration (significant) or time to angina onset (significant). Compared with beta-blocker and placebo, ivabradine improved exercise duration and time to onset of angina in patients with stable angina. However, its ability to improve exercise duration only became significant after at least 3 months of treatment. PMID:27057864

Quality of Life With Ivabradine in Patients With Angina Pectoris: The Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease Quality of Life Substudy.

PubMed

Tendera, Michal; Chassany, Olivier; Ferrari, Roberto; Ford, Ian; Steg, Philippe Gabriel; Tardif, Jean-Claude; Fox, Kim

2016-01-01

To explore the effect of ivabradine on angina-related quality of life (QoL) in patients participating in the Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients with Coronary Artery Disease (SIGNIFY) QoL substudy. QoL was evaluated in a prespecified subgroup of SIGNIFY patients with angina (Canadian Cardiovascular Society class score, ≥ 2 at baseline) using the Seattle Angina Questionnaire and a generic visual analogue scale on health status. Data were available for 4187 patients (2084 ivabradine and 2103 placebo). There were improvements in QoL in both treatment groups. The primary outcome of change in physical limitation score at 12 months was 4.56 points for ivabradine versus 3.40 points for placebo (E, 0.96; 95% confidence interval, -0.14 to 2.05; P=0.085). The ivabradine-placebo difference in physical limitation score was significant at 6 months (P=0.048). At 12 months, the visual analogue scale and the other Seattle Angina Questionnaire dimensions were higher among ivabradine-treated patients, notably angina frequency (P<0.001) and disease perception (P=0.006). Patients with the worst QoL at baseline (ie, those in the lowest tertile of score) had the best improvement in QoL for 12 months, with improvements in physical limitation and a significant reduction in angina frequency (P=0.034). The effect on QoL was maintained over the study duration, and ivabradine patients had better scores on angina frequency at every visit to 36 months. Treatment with ivabradine did not affect the primary outcome of change in physical limitation score at 12 months. It did produce consistent improvements in other self-reported QoL parameters related to angina pectoris, notably in terms of angina frequency and disease perception. URL: http://www.isrctn.com. Unique identifier: ISRCTN61576291. © 2015 American Heart Association, Inc.

Metoprolol vs ivabradine in patients with mitral stenosis in sinus rhythm.

PubMed

Agrawal, Vikas; Kumar, Niraj; Lohiya, Balalji; Sihag, Bhupendra K; Prajapati, Rajpal; Singh, T B; Subramanian, Geetha

2016-10-15

Severe mitral stenosis is usually symptomatic and is treated by BMV or surgery, whereas mild to moderate mitral stenosis is usually asymptomatic or mildly symptomatic and managed medically. Patients in the later group may become symptomatic during episodes of exercise and increased heart rate. Beta-blockers are frequently used in patients with mitral stenosis to control the heart rate and alleviate exercise-related symptoms. The objective of our study was to investigate the comparative efficacy of ivabradine versus metoprolol in patients with mitral stenosis in sinus rhythm. We studied 97 patients of mitral stenosis in sinus rhythm presented with exertional symptoms. The effectiveness of Metoprolol was compared with ivabradine in alleviating these exertional symptoms in a randomized, open label non crossover study. We also assessed various stress ECG parameters, 24 hour Holter parameters and 2D Echo parameters to objectively compare the effects of ivabradine and metoprolol in these patients. Ivabradine and metoprolol both were effective in controlling exertional symptoms. Significant improvement in objective parameters like TMT (work capacity, baseline heart rate and maximal heart rate) and 2D echocardiography (right ventricular systolic pressure) are seen with both drugs. Ivabradine controls the exertional symptoms significantly more than metoprolol. On head to head comparison there was a significant benefit of working capacity and heart rate at maximal exercise in favour of ivabradine. Ivabradine should be strongly considered in medical management of mitral stenosis patients where beta blockers are contraindicated such as reactive airway disease. The cost of ivabradine is higher than metoprolol which might possess constraints as most of the rheumatic heat disease patients belong to low socio economic status. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Heart-rate reduction by If-channel inhibition with ivabradine restores collateral artery growth in hypercholesterolemic atherosclerosis.

PubMed

Schirmer, Stephan H; Degen, Achim; Baumhäkel, Magnus; Custodis, Florian; Schuh, Lisa; Kohlhaas, Michael; Friedrich, Erik; Bahlmann, Ferdinand; Kappl, Reinhard; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

2012-05-01

Collateral arteries protect tissue from ischaemia. Heart rate correlates with vascular events in patients with arterial obstructive disease. Here, we tested the effect of heart-rate reduction (HRR) on collateral artery growth. The I(f)-channel inhibitor ivabradine reduced heart rate by 11% in wild-type and 15% in apolipoprotein E (ApoE)(-/-) mice and restored endothelium-dependent relaxation in aortic rings of ApoE(-/-) mice. Microsphere perfusion and angiographies demonstrated that ivabradine did not change hindlimb perfusion in wild-type mice but improved perfusion in ApoE(-/-) mice from 40.5 ± 15.8-60.2 ± 18.5% ligated/unligated hindlimb. Heart rate reduction (13%) with metoprolol failed to improve endothelial function and perfusion. Protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS, and eNOS activity were increased in collateral tissue following ivabradine treatment of ApoE(-/-) mice. Co-treatment with nitric oxide-inhibitor N (G)-nitro-L-arginine methyl ester abolished the effects of ivabradine on arteriogenesis. Following ivabradine, classical inflammatory cytokine expression was lowered in ApoE(-/-) circulating mononuclear cells and in plasma, but unaltered in collateral-containing hindlimb tissue, where numbers of perivascular macrophages also remained unchanged. However, ivabradine reduced expression of anti-arteriogenic cytokines CXCL10and CXCL11 and of smooth muscle cell markers smoothelin and desmin in ApoE(-/-) hindlimb tissue. Endothelial nitric oxide synthase and inflammatory cytokine expression were unchanged in wild-type mice. Ivabradine did not affect cytokine production in HUVECs and THP1 mononuclear cells and had no effect on the membrane potential of HUVECs in patch-clamp experiments. Ivabradine-induced HRR stimulates adaptive collateral artery growth. Important contributing mechanisms include improved endothelial function, eNOS activity, and modulation of inflammatory cytokine gene expression.

Acute on Chronic Ivabradine Overdose: a Case Report.

PubMed

Maskell, Kevin; Tse, Adele; Wolf, Carl E; Troendle, Michelle

2016-06-01

Ivabradine is a newly approved medication which reduces the heart rate by antagonizing the If channel. We report a case of intentional overdose on ivabradine. A 26-year-old female presented after taking 250 mg ivabradine. On arrival, her vital signs and neurologic exam were unremarkable. Within 30 min, her heart rate decreased to 31 bpm, but she remained normotensive with no change in mentation. Her bradycardia resolved after treatment with atropine. She experienced two further bradycardic episodes responsive to atropine; the second episode was associated with hypotension, responsive to a fluid bolus. For the remainder of her hospitalization, she remained hemodynamically stable without further interventions. She was dispositioned to the psychiatry service approximately 36 h post-ingestion with a heart rate of 67 bpm. Laboratory analysis confirmed a serum ivabradine concentration of 525 ng/mL, greater than 50 times the mean level in therapeutic trials. Proposed treatments for ivabradine include activated charcoal, atropine, isoproterenol, and intravenous pacing. Further study is needed to identify ideal treatment modalities.

Selective heart rate reduction with ivabradine slows ischaemia-induced electrophysiological changes and reduces ischaemia–reperfusion-induced ventricular arrhythmias

PubMed Central

Ng, Fu Siong; Shadi, Iqbal T.; Peters, Nicholas S.; Lyon, Alexander R.

2013-01-01

Heart rates during ischaemia and reperfusion are possible determinants of reperfusion arrhythmias. We used ivabradine, a selective If current inhibitor, to assess the effects of heart rate reduction (HRR) during ischaemia–reperfusion on reperfusion ventricular arrhythmias and assessed potential anti-arrhythmic mechanisms by optical mapping. Five groups of rat hearts were subjected to regional ischaemia by left anterior descending artery occlusion for 8 min followed by 10 min of reperfusion: (1) Control n = 10; (2) 1 μM of ivabradine perfusion n = 10; (3) 1 μM of ivabradine + 5 Hz atrial pacing throughout ischaemia–reperfusion n = 5; (4) 1 μM of ivabradine + 5 Hz pacing only at reperfusion; (5) 100 μM of ivabradine was used as a 1 ml bolus upon reperfusion. For optical mapping, 10 hearts (ivabradine n = 5; 5 Hz pacing n = 5) were subjected to global ischaemia whilst transmembrane voltage transients were recorded. Epicardial activation was mapped, and the rate of development of ischaemia-induced electrophysiological changes was assessed. HRR observed in the ivabradine group during both ischaemia (195 ± 11 bpm vs. control 272 ± 14 bpm, p < 0.05) and at reperfusion (168 ± 13 bpm vs. 276 ± 14 bpm, p < 0.05) was associated with reduced reperfusion ventricular fibrillation (VF) incidence (20% vs. 90%, p < 0.05). Pacing throughout ischaemia–reperfusion abolished the protective effects of ivabradine (100% VF), whereas pacing at reperfusion only partially attenuated this effect (40% VF). Ivabradine, given as a bolus at reperfusion, did not significantly affect VF incidence (80% VF). Optical mapping experiments showed a delay to ischaemia-induced conduction slowing (time to 50% conduction slowing: 10.2 ± 1.3 min vs. 5.1 ± 0.7 min, p < 0.05) and to loss of electrical excitability in ivabradine-perfused hearts (27.7 ± 4.3 min vs. 14.5 ± 0.6 min, p < 0.05). Ivabradine administered throughout ischaemia and reperfusion reduced reperfusion VF incidence through HRR. Heart rate during ischaemia is a major determinant of reperfusion arrhythmias. Heart rate at reperfusion alone was not a determinant of reperfusion VF, as neither a bolus of ivabradine nor pacing immediately prior to reperfusion significantly altered reperfusion VF incidence. This anti-arrhythmic effect of heart rate reduction during ischaemia may reflect slower development of ischaemia-induced electrophysiological changes. PMID:23402927

A Phase II Multi-Center Study of Bevacizumab in Combination with Ixabepilone in Subjects with Advanced Renal Cell Carcinoma.

PubMed

Burotto, Mauricio; Edgerly, Maureen; Velarde, Margarita; Balasubramaniam, Sanjeeve; Drabkin, Harry; Gormaz, Juan G; O'Sullivan, Ciara; Madan, Ravi; Fojo, Tito

2017-08-01

Accrual to renal cell carcinoma trials remains a challenge despite the lack of prolonged response to the available treatments.The observation of three responses among the 30 patients with median progression-free survival and overall survival of 8.3 and 15 months, respectively, indicates the combination has some activity, but it is not sufficient for further development. Treatment of metastatic renal cell carcinoma (mRCC) remains suboptimal. Preclinical data have previously shown that ixabepilone, a microtubule-stabilizing agent approved for the treatment of breast cancer, is active in taxane-sensitive and -resistant cells. In this single-arm phase II trial, we investigated a combination of ixabepilone plus bevacizumab in patients with refractory mRCC. We enrolled 30 patients with histologically confirmed mRCC, clear cell subtype, who had not been previously treated with ixabepilone or bevacizumab but had received at least one prior U.S. Food and Drug Administration (FDA)-approved treatment for renal cell carcinoma (RCC). The treatment regimen consisted of 6 mg/m 2 ixabepilone per day for 5 days and 15 mg/kg bevacizumab every 21 days. After 6 cycles, the treatment interval could be extended to every 28 days. The primary endpoint was the objective response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and the toxicity of the combination. The median number of prior therapies was two (range per patient one to five). Patients received a median of 8 cycles of ixabepilone plus bevacizumab (range 2-54). The median follow-up was 36.4 months (range 23.5-96.5). Nineteen patients (63.3%) had stable disease as a best response. Three patients (10%) had a partial response. The median PFS was 8.3 months (95% confidence interval [CI], 4.9-10.6) and the median OS was 15.0 months (95% CI, 11.3-28.8). The total number of cycle for safety evaluation was 289. Grade 3/4 adverse events (>5% incidence) included lymphopenia (16.7%), hypertension (6.7%), and leukopenia (6.7%). The combination of ixabepilone and bevacizumab was well tolerated, with modest activity in second - or later-line mRCC, but it is not recommended as a therapy without further clinical development. Alternative combinations with these agents could be explored in future studies. © AlphaMedPress; the data published online to support this summary is the property of the authors.

Impact of a pure reduction in heart rate for the treatment of left ventricular dysfunction: clinical benefits of ivabradine in the BEAUTIFUL trial.

PubMed

Danchin, Nicolas

2009-01-01

Ivabradine is an I(f) current inhibitor, that has documented antianginal efficacy. The BEAUTIFUL trial tested ivabradine against placebo in a large population of 10,917 patients in sinus rhythm, with coronary artery disease and left ventricular dysfunction, defined as left ventricular ejection fraction < or =35%. Overall, there was no impact of ivabradine on the primary end-point of the trial (cardiovascular mortality, hospitalisation for myocardial infarction, new onset or worsening heart failure). In the placebo arm of the trial, baseline heart rate > or = 70 bpm was associated with an increased risk of cardiovascular mortality, myocardial infarction, heart failure and coronary revascularisation. In the subgroup of patients with a baseline heart rate > or =70 bpm, treatment with ivabradine resulted in a significant, 36% reduction in the risk of myocardial infarction and a 20% reduction in the need for coronary revascularisation. Ivabradine was well tolerated, with an increased rate of treatment discontinuation, mainly due to bradycardia, compared with placebo. Because of its safety and efficacy to control angina, ivabradine should be considered first-line antianginal treatment in coronary artery disease patients with left ventricular dysfunction and increased heart rate, already receiving beta-blocker therapy or in whom these medications are not tolerated.

A phase II evaluation of ixabepilone in the treatment of recurrent/persistent carcinosarcoma of the uterus, an NRG Oncology/Gynecologic Oncology Group study.

PubMed

McCourt, Carolyn K; Deng, Wei; Dizon, Don S; Lankes, Heather A; Birrer, Michael J; Lomme, Michele M; Powell, Matthew A; Kendrick, James E; Saltzman, Joel N; Warshal, David; Tenney, Meaghan E; Kushner, David M; Aghajanian, Carol

2017-01-01

The primary objectives were to determine the objective response rate (ORR) and safety profile of ixabepilone in women with recurrent or persistent uterine carcinosarcoma (UCS). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Exploratory translational objectives included characterization of class III beta tubulin expression and its association with response, PFS, and OS. Patients had measurable disease; up to two prior chemotherapeutic regimens were allowed, but must have included a taxane. Women received ixabepilone 40mg/m 2 as a 3hour IV infusion on day 1 of a 21daycycle. Treatment was continued until disease progression or unacceptable toxicity occurred. Forty-two women were enrolled, with 34 eligible and evaluable. Median age was 68years. ECOG performance status was 0 in 56% of women, 38% had received radiation, and 15% had received 2 lines of chemotherapy. Overall ORR was 11.8% (4/34, 90% CI 4.2-25.1%); all were partial responses. Stable disease for at least 8weeks was achieved in 8 patients (23.5%). Median PFS and OS were 1.7mo and 7.7mo, respectively, with a median follow-up of 37mo. Six month PFS was 20.6%. Major grade≥3 toxicities were neutropenia (47%), fatigue (15%), dehydration (15%), hypertension (15%), and hyponatremia (15%); grade 2 peripheral neuropathy was reported in 18%. In this small sample size, class III beta tubulin expression in the primary tumor was not associated with the response to ixabepilone, PFS, or OS. In this cohort of women, single agent ixabepilone showed modest but insufficient clinical activity. Copyright © 2016. Published by Elsevier Inc.

A phase II evaluation of ixabepilone in the treatment of recurrent/persistent carcinosarcom a of the uterus, an NRG Oncology/Gynecologic Oncology Group study☆

PubMed Central

McCourt, Carolyn K.; Deng, Wei; Dizon, Don S.; Lankes, Heather A.; Birrer, Michael J.; Lomme, Michele M.; Powell, Matthew A.; Kendrick, James E.; Saltzman, Joel N.; Warshal, David; Tenney, Meaghan E.; Kushner, David M.; Aghajanian, Carol

2017-01-01

Background The primary objectives were to determine the objective response rate (ORR) and safety profile of ixabepilone in women with recurrent or persistent uterine carcinosarcoma (UCS). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Exploratory translational objectives included characterization of class III beta tubulin expression and its association with response, PFS, and OS. Methods Patients had measurable disease; up to two prior chemotherapeutic regimens were allowed, but must have included a taxane. Women received ixabepilone 40 mg/m2 as a 3 hour IV infusion on day 1 of a 21 day cycle. Treatment was continued until disease progression or unacceptable toxicity occurred. Results Forty-two women were enrolled, with 34 eligible and evaluable. Median age was 68 years. ECOGperformance status was 0 in 56% of women, 38% had received radiation, and 15% had received 2 lines of chemotherapy. Overall ORR was 11.8%(4/34, 90%CI 4.2–25.1%); all were partial responses. Stable disease for at least 8 weeks was achieved in 8 patients (23.5%). Median PFS and OS were 1.7 mo and 7.7 mo, respectively, with a median follow-up of 37 mo. Six month PFS was 20.6%. Major grade ≥ 3 toxicities were neutropenia (47%), fatigue (15%), dehydration (15%), hypertension (15%), and hyponatremia (15%); grade 2 peripheral neuropathy was reported in 18%. In this small sample size, class III beta tubulin expression in the primary tumor was not associated with the response to ixabepilone, PFS, or OS. Conclusion In this cohort of women, single agent ixabepilone showed modest but insufficient clinical activity. PMID:28029447

Effects of eribulin, vincristine, paclitaxel and ixabepilone on fast axonal transport and kinesin-1 driven microtubule gliding: implications for chemotherapy-induced peripheral neuropathy.

PubMed

LaPointe, Nichole E; Morfini, Gerardo; Brady, Scott T; Feinstein, Stuart C; Wilson, Leslie; Jordan, Mary Ann

2013-07-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious, painful and dose-limiting side effect of cancer drugs that target microtubules. The mechanisms underlying the neuronal damage are unknown, but may include disruption of fast axonal transport, an essential microtubule-based process that moves cellular components over long distances between neuronal cell bodies and nerve terminals. This idea is supported by the "dying back" pattern of degeneration observed in CIPN, and by the selective vulnerability of sensory neurons bearing the longest axonal projections. In this study, we test the hypothesis that microtubule-targeting drugs disrupt fast axonal transport using vesicle motility assays in isolated squid axoplasm and a cell-free microtubule gliding assay with defined components. We compare four clinically-used drugs, eribulin, vincristine, paclitaxel and ixabepilone. Of these, eribulin is associated with a relatively low incidence of severe neuropathy, while vincristine has a relatively high incidence. In vesicle motility assays, we found that all four drugs inhibited anterograde (conventional kinesin-dependent) fast axonal transport, with the potency being vincristine=ixabepilone>paclitaxel=eribulin. Interestingly, eribulin and paclitaxel did not inhibit retrograde (cytoplasmic dynein-dependent) fast axonal transport, in contrast to vincristine and ixabepilone. Similarly, vincristine and ixabepilone both exerted significant inhibitory effects in an in vitro microtubule gliding assay consisting of recombinant kinesin (kinesin-1) and microtubules composed of purified bovine brain tubulin, whereas paclitaxel and eribulin had negligible effects. Our results suggest that (i) inhibition of microtubule-based fast axonal transport may be a significant contributor to neurotoxicity induced by microtubule-targeting drugs, and (ii) that individual microtubule-targeting drugs affect fast axonal transport through different mechanisms. Copyright © 2013 Elsevier Inc. All rights reserved.

The cost effectiveness of ivabradine in the treatment of chronic heart failure from the U.K. National Health Service perspective.

PubMed

Griffiths, A; Paracha, N; Davies, A; Branscombe, N; Cowie, M R; Sculpher, M

2014-07-01

Ivabradine, a specific heart rate lowering therapy, has been shown in a randomised placebo-controlled study, Systolic HF Treatment with the If Inhibitor Ivabradine Trial (SHIfT), to significantly reduce the composite end point of cardiovascular death and hospitalisation for worsening heart failure (HF) in patients with systolic HF who are in sinus rhythm and with a heart rate ≥70 bpm, when added to optimised medical therapy (HR: 0.82, 95% CI 0.75 to 0.90, p<0.0001). We assessed the cost effectiveness of ivabradine, from a UK National Health Service perspective, based on the results of SHIfT. A Markov model estimated the cost effectiveness of ivabradine compared with standard care for two cohorts of patients with HF (heart rate ≥75 bpm in line with the EU labelled indication; and heart rate ≥70 bpm in line with the SHIfT study population). Modelled outcomes included death, hospitalisation, quality of life and New York Heart Association class. Total costs and quality adjusted life years (QALYs) for ivabradine and standard care were estimated over a lifetime horizon. The incremental cost per additional QALY for ivabradine plus standard care versus standard care has been estimated as £8498 for heart rate ≥75 bpm and £13 764 for heart rate ≥70 bpm. Ivabradine is expected to have a 95% chance of being cost-effective in the EU licensed population using the current National Institute for Health and Care Excellence cost effectiveness threshold of £20 000 per QALY. These results were robust in sensitivity analyses. This economic evaluation suggests that the use of ivabradine is likely to be cost-effective in eligible patients with HF from a UK National Health Service perspective. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effect of Ivabradine on Heart Rate and Duration of Exercise in Patients With Mild-to-Moderate Mitral Stenosis: A Randomized Comparison With Metoprolol.

PubMed

Saggu, Daljeet K; Narain, Varun S; Dwivedi, Sudhanshu K; Sethi, Rishi; Chandra, Sharad; Puri, Aniket; Saran, Ram K

2015-06-01

Symptoms in mitral stenosis (MS) are heart rate (HR) dependent. Increase in HR reduces diastolic filling period with rise in transmitral gradient. By reducing HR, beta-blockers improve hemodynamics and relieve symptoms, but the use may be limited by side effects. The present randomized crossover study looked at comparative efficacy of ivabradine and metoprolol on symptoms, hemodynamics, and exercise parameters in patients with mild-to-moderate MS (mitral valve area, 1-2 cm) in normal sinus rhythm. Baseline clinical assessment, treadmill stress testing, and an echocardiographic Doppler evaluation were performed to determine resting HR, total exercise duration, mean gradient across mitral valve, and mean pulmonary artery systolic pressure (PASP). Patients were then allocated to either metoprolol or ivabradine to maximal tolerated doses over 6 weeks (metoprolol: 100 mg twice a day, ivabradine: 10 mg twice a day). Reevaluation was done at the end of this period, and all drugs stopped for washout over 2 weeks. Thereafter, the 2 groups were crossed over to the other drug that was continued for another 6 weeks. Assessment was again performed at the end of this period. Thirty-three patients of 34 completed the protocol. Fifteen were male, mean age was 28.9 ± 6.6 years, all were in New York Heart Association class 2, and mean resting HR was 103.5 ± 7.2/min. Mean mitral valve area was 1.56 ± 0.16 cm, mean PASP was 38.1 ± 5.1 mm Hg, and mean gradient across mitral valve was 10.6 ± 1.6 mm Hg. Significant decrease in baseline and peak exercise HR was observed at the end of follow-up with both drugs. Reduction in mitral valve gradient after ivabradine (42%) and metoprolol (37%) and reduction in PASP after both ivabradine (23%) and metoprolol (27%) were to a similar extent. Significant reduction in total exercise duration after both ivabradine and metoprolol therapy was observed. One patient developed blurring of vision with ivabradine therapy but did not require discontinuation of drug. An improvement in dyspnea of one grade was observed in all the patients by treatment with both ivabradine and metoprolol. Both metoprolol and ivabradine reduced symptoms and improved hemodynamics significantly from baseline to a similar extent. Ivabradine thus can be used effectively and safely in patients with MS in normal sinus rhythm who are intolerant or contraindicated for beta-blocker therapy.

Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia.

PubMed

Vaillant, Fanny; Lauzier, Benjamin; Ruiz, Matthieu; Shi, Yanfen; Lachance, Dominic; Rivard, Marie-Eve; Bolduc, Virginie; Thorin, Eric; Tardif, Jean-Claude; Des Rosiers, Christine

2016-10-01

While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker I f current, vs. β-blockers like metoprolol. This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB +/+ ;LDLR -/- ). Following a longitudinal study design, we used 3- and 6-mo-old mice, untreated or treated for 3 mo with ivabradine or metoprolol. Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with 13 C-labeled substrates to assess substrate fluxes through energy metabolic pathways. Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. Despite similar HRR, ivabradine, but not metoprolol, preserved cardiac function and glucose metabolism during disease progression. Copyright © 2016 the American Physiological Society.

A comparative study of ivabradine and atenolol in patients with moderate mitral stenosis in sinus rhythm.

PubMed

Rajesh, Gopalan Nair; Sajeer, Kalathingathodika; Sajeev, Chakanalil Govindan; Bastian, Cicy; Vinayakumar, Desabandhu; Muneer, Kader; Haridasan, Vellani; Mathew, Dolly; George, Biju; Krishnan, Mangalath Narayanan

2016-01-01

Beta-blockers are frequently used in patients with mitral stenosis to control the heart rate and alleviate exercise-related symptoms. The objective of our study was to examine whether ivabradine was superior to atenolol for achieving higher exercise capacity in patients with moderate mitral stenosis in sinus rhythm. We also evaluated their effects on left ventricular myocardial performance index (MPI). Eighty-two patients with moderate mitral stenosis in sinus rhythm were randomized to receive ivabradine (n=42) 5mg twice daily or atenolol (n=40) 50mg daily for 6 weeks. Transthoracic echocardiography and treadmill test were performed at baseline and after completion of 6 weeks of treatment. Mean total exercise duration in seconds markedly improved in both study groups at 6 weeks (298.57±99.05s vs. 349.12±103.53s; p=0.0001 in ivabradine group, 290.90±92.42s vs. 339.90±99.84s; p=0.0001 in atenolol group). On head-to-head comparison, there was no significant change in improvement of exercise time between ivabradine and atenolol group (p=0.847). Left ventricular MPI did not show any significant change from baseline and at 6 weeks in both drug groups (49.8%±8% vs. 48.3%±7% in ivabradine group, 52.9%±10% vs. 50.9%±10% in atenolol groups; p=0.602). Ivabradine or atenolol can be used for heart rate control in patients with moderate mitral stenosis in sinus rhythm. Ivabradine is not superior to atenolol for controlling heart rate or exercise capacity. Left ventricular MPI was unaffected by either of the drugs. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Heart Rate Reduction With Ivabradine Protects Against Left Ventricular Remodeling by Attenuating Infarct Expansion and Preserving Remote-Zone Contractile Function and Synchrony in a Mouse Model of Reperfused Myocardial Infarction.

PubMed

O'Connor, Daniel M; Smith, Robert S; Piras, Bryan A; Beyers, Ronald J; Lin, Dan; Hossack, John A; French, Brent A

2016-04-22

Ivabradine selectively inhibits the pacemaker current of the sinoatrial node, slowing heart rate. Few studies have examined the effects of ivabradine on the mechanical properties of the heart after reperfused myocardial infarction (MI). Advances in ultrasound speckle-tracking allow strain analyses to be performed in small-animal models, enabling the assessment of regional mechanical function. After 1 hour of coronary occlusion followed by reperfusion, mice received 10 mg/kg per day of ivabradine dissolved in drinking water (n=10), or were treated as infarcted controls (n=9). Three-dimensional high-frequency echocardiography was performed at baseline and at days 2, 7, 14, and 28 post-MI. Speckle-tracking software was used to calculate intramural longitudinal myocardial strain (Ell) and strain rate. Standard deviation time to peak radial strain (SD Tpeak Err) and temporal uniformity of strain were calculated from short-axis cines acquired in the left ventricular remote zone. Ivabradine reduced heart rate by 8% to 16% over the course of 28 days compared to controls (P<0.001). On day 28 post-MI, the ivabradine group was found to have significantly smaller end-systolic volumes, greater ejection fraction, reduced wall thinning, and greater peak Ell and Ell rate in the remote zone, as well as globally. Temporal uniformity of strain and SD Tpeak Err were significantly smaller in the ivabradine-treated group by day 28 (P<0.05). High-frequency ultrasound speckle-tracking demonstrated decreased left ventricular remodeling and dyssynchrony, as well as improved mechanical performance in remote myocardium after heart rate reduction with ivabradine. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

A case of atrial tachycardia treated with ivabradine as bridge to ablation.

PubMed

Meles, Ester; Carbone, Claudio; Maggiolini, Stefano; Moretti, Paolo; DE Carlini, Caterina C; Gentile, Gaetano; Gnecchi-Ruscone, Tomaso

2015-05-01

Ivabradine is indicated in cardiac failure and ischemia to reduce sinus rate by inhibition of the pacemaker I(f) current in sinoatrial node. We report a case of an 18-year-old woman with left atrial tachyarrhythmia resistant to several antiarrhythmic drugs and to electric cardioversion who responded only to ivabradine, which significantly reduced heart rate without abolishing the arrhythmia itself. An ectopic focus in the ostium of left pulmonary veins was found and the patient was successfully ablated. We suggest that ivabradine might be therefore useful in the treatment of supraventricular tachyarrhythmias due to an enhanced automaticity. © 2015 Wiley Periodicals, Inc.

Gateways to clinical trials.

PubMed

Tomillero, A; Moral, M A

2009-03-01

ABT-869, Acadesine, Acetylsalicylic acid/omeprazole, Adefovir, Adefovir dipivoxil, AEG-35156, Agatolimod sodium, Albiglutide, Alemtuzumab, Alipogene tiparvovec, Alogliptin benzoate, AMG-386, Amrubicin hydrochloride, Apremilast, Aripiprazole, Asoprisnil, Atorvastatin/fenofibrate, AVN-944, Axitinib; Belinostat, Bevacizumab, BHT-3021, BI-2536, Biapenem, Bilastine, Biphasic insulin aspart, Blinatumomab, Bortezomib, Bosentan; Catumaxomab, CD-NP, Cediranib, Certolizumab pegol, Cetuximab, Choline fenofibrate, Ciclesonide, CK-1827452,Clevudine, Clofarabine, CSL-360, CYT-997; Dapagliflozin, Darinaparsin, Denosumab, Densiron 68, Desloratadine, Dulanermin; Edoxaban tosilate, Emtricitabine, Entecavir, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Fidaxomicintiacumiv, Fulvestrant; G-207, GCR-8015, Gefitinib, Ghrelin (human), Glufosfamide; HPV16L1E7CVLP; Ibutamoren mesilate, Imatinib mesylate, Insulin detemir, Insulin glargine, Iodine (I131) tositumomab, Istaroxime, ITMN-191, Ixabepilone; JZP-4, Lenalidomide; Levetiracetam, Linaclotide acetate, Liposomal cytarabine/daunorubicin, Liposomal doxorubicin, Liraglutide, LY-518674; Milatuzumab, MMR-V, Motesanib diphosphate, Mycophenolic acid sodium salt; Niacin/simvastatin; Obatoclax mesylate, Odanacatib; Paclitaxel nanoparticles, Paclitaxel-eluting stent, Pazufloxacin, PBT-2, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pemetrexed disodium, Perampanel, PfCP2.9, Pitavastatin calcium, Poly I:CLC, Pomalidomide, Pralatrexate, Pramlintide acetate, Prucalopride; rhGAD65, Roflumilast; RTS,S/AS02D; SCH-530348, Semagacestat, Sirolimus-eluting coronary stent, Sirolimus-Eluting Stent, SIR-Spheres, Sivelestat sodium hydrate, Sorafenib, Sunitinib malate; Tadalafil, Tafluprost, Tanespimycin, Teduglutide, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tiotropium bromide, TMC-435350, Tositumomab/iodine (I131) tositumomab, Travoprost/timolol, Triciribine phosphate; Vandetanib, VIA-2291, Vinflunine, Vorinostat; XL-019; Yttrium 90 (90Y) ibritumomab tiuxetan. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

[Efficacy of ivabradine in combination therapy for complicated acute coronary syndrome in patients with type 2 diabetes mellitus].

PubMed

Kondrat'ev, A I; Dolgikh, V T; Stotskiĭ, A O

2010-01-01

To study the effect of ivabradine (coraxan, Servier) as part of combination therapy on the clinical manifestations of acute left ventricular failure (ALVF) in Braunwald class II-IIIB unstable angina in patients with type 2 diabetes mellitus (T2DM). Thirty-six T2DM patients (mean age 56 + 4.3 years) with a diagnosis of acute coronary syndrome were examined. Eighteen healthy individuals were examined as an age- and gender-matched control group. Metabolic, hemodynamic, and electrophysiological parameters were studied in all the patients on hospital stay days I and S. Ivabradine used in combination therapy for unstable angina caused reductions in the clinical manifestations of ALVF, heart rate, the number of myocardial ischemic episodes. In the ivabradine-treated patients, left ventricular ejection fraction showed a significant trend for increase. No adverse reactions were recorded. Ivabradine therapy demonstrated antiischemic and antianginal efficiencies and a good tolerability, without leading to the development of tolerance and without being followed by the development of the withdrawal syndrome.

Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2005-06-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, acyline, adalimumab, adenosine triphosphate, AEE-788, AIDSVAX gp120 B/B, AK-602, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alprazolam, amdoxovir, AMG-162, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminophylline hydrate, anakinra, anecortave acetate, anti-CTLA-4 MAb, APC-8015, aripiprazole, aspirin, atazanavir sulfate, atomoxetine hydrochloride, atorvastatin calcium, atrasentan, AVE-5883, AZD-2171; Betamethasone dipropionate, bevacizumab, bimatoprost, biphasic human insulin (prb), bortezomib, BR-A-657, BRL-55730, budesonide, busulfan; Calcipotriol, calcipotriol/betamethasone dipropionate, calcium folinate, capecitabine, capravirine, carmustine, caspofungin acetate, cefdinir, certolizumab pegol, CG-53135, chlorambucil, ciclesonide, ciclosporin, cisplatin, clofarabine, clopidogrel hydrogensulfate, clozapine, co-trimoxazole, CP-122721, creatine, CY-2301, cyclophosphamide, cypher, cytarabine, cytolin; D0401, darbepoetin alfa, darifenacin hydrobromide, DASB, desipramine hydrochloride, desloratadine, desvenlafaxine succinate, dexamethasone, didanosine, diquafosol tetrasodium, docetaxel, doxorubicin hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecallantide, efalizumab, efavirenz, eletriptan, emtricitabine, enfuvirtide, enoxaparin sodium, estramustine phosphate sodium, etanercept, ethinylestradiol, etonogestrel, etonogestrel/ethinylestradiol, etoposide, exenatide; Famciclovir, fampridine, febuxostat, filgrastim, fludarabine phosphate, fluocinolone acetonide, fluorouracil, fluticasone propionate, fluvastatin sodium, fondaparinux sodium; Gaboxadol, gamma-hydroxybutyrate sodium, gefitinib, gelclair, gemcitabine, gemfibrozil, glibenclamide, glyminox; Haloperidol, heparin sodium, HPV 16/HPV 18 vaccine, human insulin, human insulin; Icatibant, imatinib mesylate, indium 111 (111In) ibritumomab tiuxetan, infliximab, INKP-100, iodine (I131) tositumomab, IoGen, ipratropium bromide, ixabepilone; L-870810, lamivudine, lapatinib, laquinimod, latanoprost, levonorgestrel, licochalcone a, liposomal doxorubicin, lopinavir, lopinavir/ritonavir, lorazepam, lovastatin; Maraviroc, maribavir, matuzumab, MDL-100907, melphalan, methotrexate, methylprednisolone, mitomycin, mitoxantrone hydrochloride, MK-0431, MN-001, MRKAd5 HIV-1 gag/pol/nef, MRKAd5gag, MVA.HIVA, MVA-BN Nef, MVA-Muc1-IL-2, mycophenolate mofetil; Nelfinavir mesilate, nesiritide, NSC-330507; Olanzapine, olmesartan medoxomil, omalizumab, oral insulin, osanetant; PA-457, paclitaxel, paroxetine, paroxetine hydrochloride, PCK-3145, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, perillyl alcohol, pexelizumab, pimecrolimus, pitavastatin calcium, porfiromycin, prasterone, prasugrel, pravastatin sodium, prednisone, pregabalin, prinomastat, PRO-2000, propofol, prostate cancer vaccine; Rasagiline mesilate, rhBMP-2/ACS, rhBMP-2/BCP, rhC1, ribavirin, rilpivirine, ritonavir, rituximab, Ro-26-9228, rosuvastatin calcium, rosuvastatin sodium, rubitecan; Selodenoson, simvastatin, sirolimus, sitaxsentan sodium, sorafenib, SS(dsFv)-PE38, St. John's Wort extract, stavudine; Tacrolimus, tadalafil, tafenoquine succinate, talaglumetad, tanomastat, taxus, tegaserod maleate, telithromycin, tempol, tenofovir, tenofovir disoproxil fumarate, testosterone enanthate, TH-9507, thalidomide, tigecycline, timolol maleate, tiotropium bromide, tipifarnib, torcetrapib, trabectedin, travoprost, travoprost/timolol, treprostinil sodium; Valdecoxib, vardenafil hydrochloride hydrate, varenicline, VEGF-2 gene therapy, venlafaxine hydrochloride, vildagliptin, vincristine sulfate, voriconazole, VRX-496, VX-385; Warfarin sodium; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, zidovudine. Copyright (c) 2005 Prous Science. All rights reserved.

The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease.

PubMed

Gloekler, Steffen; Traupe, Tobias; Stoller, Michael; Schild, Deborah; Steck, Hélène; Khattab, Ahmed; Vogel, Rolf; Seiler, Christian

2014-01-01

To evaluate the effect of heart rate reduction by ivabradine on coronary collateral function in patients with chronic stable coronary artery disease (CAD). This was a prospective randomised placebo-controlled monocentre trial in a university hospital setting. 46 patients with chronic stable CAD received placebo (n=23) or ivabradine (n=23) for the duration of 6 months. The main outcome measure was collateral flow index (CFI) as obtained during a 1 min coronary artery balloon occlusion at study inclusion (baseline) and at the 6-month follow-up examination. CFI is the ratio between simultaneously recorded mean coronary occlusive pressure divided by mean aortic pressure both subtracted by mean central venous pressure. During follow-up, heart rate changed by +0.2±7.8 beats/min in the placebo group, and by -8.1±11.6 beats/min in the ivabradine group (p=0.0089). In the placebo group, CFI decreased from 0.140±0.097 at baseline to 0.109±0.067 at follow-up (p=0.12); it increased from 0.107±0.077 at baseline to 0.152±0.090 at follow-up in the ivabradine group (p=0.0461). The difference in CFI between the 6-month follow-up and baseline examination amounted to -0.031±0.090 in the placebo group and to +0.040±0.094 in the ivabradine group (p=0.0113). Heart rate reduction by ivabradine appears to have a positive effect on coronary collateral function in patients with chronic stable CAD. NCT01039389.

Ivabradine: Current and Future Treatment of Heart Failure.

PubMed

Thorup, Lene; Simonsen, Ulf; Grimm, Daniela; Hedegaard, Elise R

2017-08-01

In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end-diastolic pressure. Current treatments for HF with reduced ejection fraction (HFrEF) include angiotensin-converting enzyme (ACE) inhibitors, angiotension receptor type 1 (AT 1 ) antagonists, β-adrenoceptor antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT 1 receptor antagonist and neprilysin inhibitor. In HF, the risk of readmission for hospital and mortality is markedly higher with a heart rate (HR) above 70 bpm. Here, we review the evidence regarding the use of ivabradine for lowering HR in HF. Ivabradine is a blocker of an I funny current (I(f)) channel and causes rate-dependent inhibition of the pacemaker activity in the sinoatrial node. In clinical trials of HFrEF, treatment with ivabradine seems to improve clinical outcome, for example improved ejection fraction (EF) and less readmission for hospital, but the effect appears most pronounced in patients with HRs above 70 bpm, while the effect on cardiovascular death appears less consistent. The adverse effects of ivabradine include bradycardia, atrial fibrillation and visual disturbances, but ivabradine avoids the negative inotrope effects observed with β-adrenoceptor antagonists. In conclusion, in patients with stable HFrEF with EF<35% and HR above 70 bpm, ivabradine improves the outcome and might be a first choice of therapy, if beta-adrenoceptor antagonists are not tolerated. Further studies must show whether that can be extended to HF patients with preserved EF. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Heart rate at baseline influences the effect of ivabradine on cardiovascular outcomes in chronic heart failure: analysis from the SHIFT study.

PubMed

Böhm, Michael; Borer, Jeffrey; Ford, Ian; Gonzalez-Juanatey, Jose R; Komajda, Michel; Lopez-Sendon, Jose; Reil, Jan-Christian; Swedberg, Karl; Tavazzi, Luigi

2013-01-01

We analysed the effect of ivabradine on outcomes in heart failure (HF) patients on recommended background therapies with heart rates ≥75 bpm and <75 bpm in the SHIFT trial. A cut-off value of ≥75 bpm was chosen by the EMEA for approval for the use of ivabradine in chronic heart failure. The SHIFT population was divided by baseline heart rate ≥75 or <75 bpm. The effect of ivabradine was analysed for primary composite endpoint (cardiovascular death or HF hospitalization) and other endpoints. In the ≥75 bpm group, ivabradine reduced primary endpoint (HR 0.76, 95 % CI 0.68-0.85, P < 0.0001), all-cause mortality (HR 0.83, 95 % CI, 0.72-0.96, P = 0.0109), cardiovascular mortality (HR 0.83, 95 % CI, (0.71-0.97, P = 0.0166), HF death (HR 0.61, 95 % CI, 0.46-0.81, P < 0.0006), and HF hospitalization (HR 0.70, 95 % CI, 0.61-0.80, P < 0.0001). Risk reduction depended on heart rate after 28 days, with the best protection for heart rates <60 bpm or reductions >10 bpm. None of the endpoints was significantly reduced in the <75 bpm group, though there were trends for risk reductions in HF death and hospitalization for heart rate <60 bpm and reductions >10 bpm. Ivabradine was tolerated similarly in both groups. The effect of ivabradine on outcomes is greater in patients with heart rate ≥75 bpm with heart rates achieved <60 bpm or heart rate reductions >10 bpm predicting best risk reduction. Our findings emphasize the importance of identification of high-risk HF patients by high heart rates and their treatment with heart rate-lowering drugs such as ivabradine.

Real-life indications to ivabradine treatment for heart rate optimization in patients with chronic systolic heart failure.

PubMed

Tondi, Lara; Fragasso, Gabriele; Spoladore, Roberto; Pinto, Giuseppe; Gemma, Marco; Slavich, Massimo; Godino, Cosmo; Salerno, Anna; Montanaro, Claudia; Margonato, Alberto

2018-05-11

: Ivabradine is a selective and specific inhibitor of If current. With its pure negative chronotropic action, it is recommended by European Society of Cardiology and American College of Cardiology/American Heart Association guidelines in symptomatic heart failure patients (NYHA ≥ 2) with ejection fraction 35% or less, sinus rhythm and heart rate (HR) at least 70 bpm, despite maximally titrated β-blocker therapy. Data supporting this indication mainly derive from the SHIFT study, in which ivabradine reduced the combined endpoint of mortality and hospitalization, despite the fact that only 26% of patients enrolled were on optimal β-blocker doses. The aim of the present analysis is to establish the real-life eligibility for ivabradine in a population of patients with systolic heart failure, regularly attending a single heart failure clinic and treated according to guideline-directed medical therapy (GDMT). The clinical cards of 308 patients with heart failure with reduced ejection fraction (HFrEF) through a 68-month period of observation were retrospectively analyzed. GDMT, including β-blocker up-titration to maximal tolerated dose, was implemented during consecutive visits at variable intervals. Demographic, clinical and echocardiographic data were collected at each visit, together with 12-leads ECG and N-terminal pro-B-type natriuretic peptide levels. Out of 308 analyzed HFrEF patients, 220 (71%) were on effective β-blocker therapy, up-titrated to effective/maximal tolerated dose (55 ± 28% of maximal dose) (HR 67 ± 10 bpm). Among the remaining 88 patients, 10 (3.2%) were on maximally tolerated β blocker and ivabradine; 21 patients (6.8%), despite being on maximal tolerated β-blocker dose, had still HR ≥70 bpm, ejection fraction 35% or less and were symptomatic NYHA ≥2, being therefore eligible for ivabradine treatment. The remaining 57 (18%) patients were not on β blocker due to either intolerance or major contraindications. Among them, 13 (4%) were taking ivabradine alone. Of the final 44 (14%) patients, 27 (9%) showed an inadequate HR control (74 ± 6 bpm). Of these, only eight (3%) patients resulted to be eligible for ivabradine introduction according to HR and ejection fraction parameters. Overall ivabradine was indicated in 52 patients (16.8%) out of 308 enrolled.In conclusion, in a carefully managed population of patients with moderate and stable HFrEF, in which optimal GDMT is properly attained, indication to ivabradine treatment is around 17%.

Ivabradine in stable coronary artery disease without clinical heart failure.

PubMed

Fox, Kim; Ford, Ian; Steg, Philippe Gabriel; Tardif, Jean-Claude; Tendera, Michal; Ferrari, Roberto

2014-09-18

An elevated heart rate is an established marker of cardiovascular risk. Previous analyses have suggested that ivabradine, a heart-rate-reducing agent, may improve outcomes in patients with stable coronary artery disease, left ventricular dysfunction, and a heart rate of 70 beats per minute or more. We conducted a randomized, double-blind, placebo-controlled trial of ivabradine, added to standard background therapy, in 19,102 patients who had both stable coronary artery disease without clinical heart failure and a heart rate of 70 beats per minute or more (including 12,049 patients with activity-limiting angina [class ≥II on the Canadian Cardiovascular Society scale, which ranges from I to IV, with higher classes indicating greater limitations on physical activity owing to angina]). We randomly assigned patients to placebo or ivabradine, at a dose of up to 10 mg twice daily, with the dose adjusted to achieve a target heart rate of 55 to 60 beats per minute. The primary end point was a composite of death from cardiovascular causes or nonfatal myocardial infarction. At 3 months, the mean (±SD) heart rate of the patients was 60.7±9.0 beats per minute in the ivabradine group versus 70.6±10.1 beats per minute in the placebo group. After a median follow-up of 27.8 months, there was no significant difference between the ivabradine group and the placebo group in the incidence of the primary end point (6.8% and 6.4%, respectively; hazard ratio, 1.08; 95% confidence interval, 0.96 to 1.20; P=0.20), nor were there significant differences in the incidences of death from cardiovascular causes and nonfatal myocardial infarction. Ivabradine was associated with an increase in the incidence of the primary end point among patients with activity-limiting angina but not among those without activity-limiting angina (P=0.02 for interaction). The incidence of bradycardia was higher with ivabradine than with placebo (18.0% vs. 2.3%, P<0.001). Among patients who had stable coronary artery disease without clinical heart failure, the addition of ivabradine to standard background therapy to reduce the heart rate did not improve outcomes. (Funded by Servier; SIGNIFY Current Controlled Trials number, ISRCTN61576291.).

Ivabradine in combination with beta-blocker therapy for the treatment of stable angina pectoris in every day clinical practice.

PubMed

Koester, Ralf; Kaehler, Jan; Ebelt, Henning; Soeffker, Gerold; Werdan, Karl; Meinertz, Thomas

2010-10-01

The anti-anginal efficacy of the selective I(f) inhibitor ivabradine has been demonstrated in controlled clinical trials. However, there is limited information about the safety and efficacy of a combined treatment of ivabradine with beta-blockers, particularly outside of clinical trials in every day practice. This analysis from the REDUCTION study evaluated the safety and efficacy of a combined therapy of beta-blockers and ivabradine in every day practice. In this multi-center study 4,954 patients with stable angina pectoris were treated with ivabradine in every day routine practice and underwent a clinical follow-up for 4 months. 344 of these patients received a co-medication with beta-blockers. Heart rate (HR), angina pectoris episodes, nitrate consumption, overall efficacy and tolerance were analyzed. After 4 months of treatment with ivabradine HR was reduced by 12.4 ± 11.6 bpm from 84.3 ± 14.6 to 72.0 ± 9.9 bpm, p < 0.0001. Angina pectoris episodes were reduced from 2.8 ± 3.3 to 0.5 ± 1.3 per week, p < 0.0001. Consumption of short-acting nitrates was reduced from 3.7 ± 5.6 to 0.7 ± 1.7 units per week, p < 0.0001. Five patients (1.5%) reported adverse drug reactions (ADR). The most common ADR were nausea and dizziness (<0.6% each). There was no clinically relevant bradycardia. Efficacy and tolerance were graded as 'very good/good' for 96 and 99% of the patients treated. Ivabradine effectively reduces heart rate and angina pectoris in combination with beta-blockers and is well tolerated by patients in every day practice.

Role of ivabradine and heart rate lowering in chronic heart failure: guideline update.

PubMed

Chow, Sheryl L; Page, Robert Lee; Depre, Christophe

2018-06-14

This review summarizes the current management of heart failure (HF) in patients with reduced ejection fraction and the potential role of heart rate lowering agents in select populations, as recommended in the updated guidelines. Areas covered: PubMed was searched for studies that evaluated the role of heart rate lowering or ivabradine in HF management. Expert commentary: Targeting heart rate may offer benefit when added to renin-angiotensin aldosterone antagonists, and beta-blockers. Ivabradine is a heart rate lowering agent that acts on the funny current (I f ) in the sinoatrial node, thereby reducing heart rate without directly affecting cardiac contraction and relaxation. Clinical data from a phase 3 trial demonstrated that ivabradine reduced the composite endpoint of cardiovascular death or hospital admission for worsening systolic HF, while maintaining an acceptable safety profile in patients receiving standard of care therapy. These data, in addition to more recently published guidelines, suggest ivabradine as a promising new treatment option for lowering heart rate after optimizing standard therapy in select patients with chronic HF.

Budget Impact of Adding Ivabradine to Standard of Care in Patients with Chronic Systolic Heart Failure in the United States.

PubMed

Borer, Jeffrey S; Kansal, Anuraag R; Dorman, Emily D; Krotneva, Stanimira; Zheng, Ying; Patel, Harshali K; Tavazzi, Luigi; Komajda, Michel; Ford, Ian; Böhm, Michael; Kielhorn, Adrian

2016-09-01

Heart failure (HF) costs $21 billion annually in direct health care costs, 80% of which is directly attributable to hospitalizations. The SHIFT clinical study demonstrated that ivabradine plus standard of care (SoC) reduced HF-related and all-cause hospitalizations compared with SoC alone. To estimate the budget impact of ivabradine from a U.S. commercial payer perspective. A budget impact model estimated the per-member-per month (PMPM) impact of introducing ivabradine to existing formularies by comparing a reference scenario (SoC) and a new drug scenario (ivabradine + SoC) in hypothetical 1 million-member commercial and Medicare Advantage plans. In both scenarios, U.S. claims data were used for the reference cumulative annual rates of hospitalizations (HF, non-HF cardiovascular [CV], and non-CV), and hospitalization rates were adjusted using SHIFT data. The model controlled for mortality risk using SHIFT and U.S. life table data, and hospitalization costs were obtained from U.S. claims data: HF-related = $37,507; non-HF CV = $28,951; and non-CV = $17,904. The annualized wholesale acquisition cost of ivabradine was $4,500, with baseline use for this new drug at 2%, increasing 2% per year. Based on the approved U.S. indication, approximately 2,000 commercially insured patients from a 1 million-member commercial plan were eligible to receive ivabradine. Ivabradine resulted in a PMPM cost savings of $0.01 and $0.04 in years 1 and 3 of the core model, respectively. After including the acquisition price for ivabradine, the model showed a decrease in total costs in the commercial ($991,256 and $474,499, respectively) and Medicare populations ($13,849,262 and $4,280,291, respectively) in year 1. This decrease was driven by ivabradine's reduction in hospitalization rates. For the core model, the estimated pharmacy-only PMPM in year 1 was $0.01 for the commercial population and $0.24 for the Medicare Advantage population. Adding ivabradine to SoC led to lower average annual treatment costs. The negative PMPM budget impact indicates that ivabradine is an affordable option for U.S. payers. This study was funded by Amgen. Patel is employed by Amgen; Kielhorn was employed by Amgen at the time of the study but is no longer affiliated with Amgen. Borer, Böhm, Ford, and Komajda have received scientific support, consultative fees, and/or speakers honoraria from Servier and Amgen in connection with SHIFT, the trial underlying this analysis. Borer also has received consultative fees from Celladon, Pfizer, ARMGO, Cardiorentis, Novartis, and Takeda USA. Kansal, Dorman, Krotneva, and Zheng are employees of Evidera, which was hired to assist with this study. Tavazzi has received research grants and consultation fees from Servier in connection with this study and has had advisory board memberships with Boston Scientific, Servier, Cardiorentis, Medtronic, St. Jude Medical, and CVie Therapeutics. Study concept and design were contributed by Dorman and Keilhorn, along with the other authors. Tavazzi, Komajda, Ford, BÖhm, and Borer oversaw collection of the data. Tavazzi, Komajda, Ford, BÖhm, and Borer (along with Karl Swedberg) formed the Executive Committee of SHIFT, the trial underlying this analysis. The manuscript was written by Kansal, along with the other authors, and revised by Borer and Patel, with assistance from the other authors.

Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.

PubMed

Fox, Kim; Ford, Ian; Steg, P Gabriel; Tendera, Michal; Ferrari, Roberto

2008-09-06

Ivabradine specifically inhibits the I(f) current in the sinoatrial node to lower heart rate, without affecting other aspects of cardiac function. We aimed to test whether lowering the heart rate with ivabradine reduces cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular systolic dysfunction. Between December, 2004, and December, 2006, we screened 12 473 patients at 781 centres in 33 countries. We enrolled 10 917 eligible patients who had coronary artery disease and a left-ventricular ejection fraction of less than 40% in a randomised, double-blind, placebo-controlled, parallel-group trial. 5479 patients received 5 mg ivabradine, with the intention of increasing to the target dose of 7.5 mg twice a day, and 5438 received matched placebo in addition to appropriate cardiovascular medication. The primary endpoint was a composite of cardiovascular death, admission to hospital for acute myocardial infarction, and admission to hospital for new onset or worsening heart failure. We analysed patients by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00143507. Mean heart rate at baseline was 71.6 (SD 9.9) beats per minute (bpm). Median follow-up was 19 months (IQR 16-24). Ivabradine reduced heart rate by 6 bpm (SE 0.2) at 12 months, corrected for placebo. Most (87%) patients were receiving beta blockers in addition to study drugs, and no safety concerns were identified. Ivabradine did not affect the primary composite endpoint (hazard ratio 1.00, 95% CI 0.91-1.1, p=0.94). 1233 (22.5%) patients in the ivabradine group had serious adverse events, compared with 1239 (22.8%) controls (p=0.70). In a prespecified subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not affect the primary composite outcome (hazard ratio 0.91, 95% CI 0.81-1.04, p=0.17), cardiovascular death, or admission to hospital for new-onset or worsening heart failure. However, it did reduce secondary endpoints: admission to hospital for fatal and non-fatal myocardial infarction (0.64, 95% CI 0.49-0.84, p=0.001) and coronary revascularisation (0.70, 95% CI 0.52-0.93, p=0.016). Reduction in heart rate with ivabradine does not improve cardiac outcomes in all patients with stable coronary artery disease and left-ventricular systolic dysfunction, but could be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients who have heart rates of 70 bpm or greater.

Role of ivabradine in management of stable angina in patients with different clinical profiles

PubMed Central

Kaski, Juan Carlos; Gloekler, Steffen; Ferrari, Roberto; Fox, Kim; Lévy, Bernard I; Komajda, Michel; Vardas, Panos; Camici, Paolo G

2018-01-01

In chronic stable angina, elevated heart rate contributes to the development of symptoms and signs of myocardial ischaemia by increasing myocardial oxygen demand and reducing diastolic perfusion time. Accordingly, heart rate reduction is a well-known strategy for improving both symptoms of myocardial ischaemia and quality of life (QOL). The heart rate-reducing agent ivabradine, a direct and selective inhibitor of the I f current, decreases myocardial oxygen consumption while increasing diastolic time, without affecting myocardial contractility or coronary vasomotor tone. Ivabradine is indicated for treatment of stable angina and chronic heart failure (HF). This review examines available evidence regarding the efficacy and safety of ivabradine in stable angina, when used as monotherapy or in combination with beta-blockers, in particular angina subgroups and in patients with stable angina with left ventricular systolic dysfunction (LVSD) or HF. Trials involving more than 45 000 patients receiving treatment with ivabradine have shown that this agent has antianginal and anti-ischaemic effects, regardless of age, sex, severity of angina, revascularisation status or comorbidities. This heart rate-lowering agent might also improve prognosis, reduce hospitalisation rates and improve QOL in angina patients with chronic HF and LVSD. PMID:29632676

Evolving therapies for the management of chronic and acute decompensated heart failure.

PubMed

Cook, Jennifer C; Tran, Richard H; Patterson, J Herbert; Rodgers, Jo E

2016-11-01

The pharmacology, clinical efficacy, and safety profiles of evolving therapies for the management of chronic heart failure (HF) and acute decompensated heart failure (ADHF) are described. HF confers a significant financial burden despite the widespread use of traditional guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone receptor antagonists, and the rates of HF-related mortality and hospitalization have remained unacceptably high. In response to a demand for novel pharmacologic agents, several therapeutic compounds have recently gained approval or are currently under review by the Food and Drug Administration. Sacubitril-valsartan has demonstrated benefit in reducing cardiovascular mortality and HF-related hospitalizations in clinical trials, while ivabradine and ferric carboxymaltose have proven efficacious in reducing HF-related hospitalizations. Lastly, the role of serelaxin in ADHF is currently under investigation in an ongoing Phase III study. While large, outcome-driven clinical trials are fundamental in informing the clinical application of these therapeutic agents, careful patient selection is imperative to ensuring similar outcomes postmarketing. In addition, optimization of current guideline-directed medical therapy remains essential as new therapies emerge and are incorporated into guideline recommendations. Additional therapeutic agents currently undergoing investigation include bucindolol hydrochloride, cimaglermin alfa, nitroxyl, omecamtiv mecarbil, TRV027, and ularitide. Clinical practitioners should remain abreast of emerging literature so that new therapeutic entities are optimally applied and positive patient outcomes are achieved. Recently introduced agents for the treatment of patients with HF include sacubitril-valsartan, ivabradine, and ferric carboxymaltose. Additional agents worthy of attention include serelaxin and other therapies currently under investigation. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Bradycardia and atrial fibrillation in patients with stable coronary artery disease treated with ivabradine: an analysis from the SIGNIFY study.

PubMed

Fox, Kim; Ford, Ian; Steg, Philippe Gabriel; Tardif, Jean-Claude; Tendera, Michal; Ferrari, Roberto

2015-12-07

The aim of this study was to determine the impact of emergent bradycardia and atrial fibrillation (AF) on cardiovascular outcomes in 19 083 patients with stable coronary artery disease (CAD) receiving ivabradine or placebo (SIGNIFY, Study assessInG the morbidity-mortality beNefits of the If inhibitor ivabradine in patients with coronarY artery disease). Emergent bradycardia (resting heart rate <50 b.p.m. on 12-lead electrocardiogram) with ivabradine was reported in 3572 patients (37.4%) overall, and in 2242 (37.2%) patients with Canadian Cardiovascular Society (CCS) class ≥ 2 angina. There was no difference in outcomes over the course of the study in ivabradine-treated patients with and without emergent bradycardia in the whole population (2.5 vs. 2.9% per year, respectively, for primary composite endpoint of cardiovascular death or non-fatal myocardial infarction) or in the angina subgroup (2.5 vs. 3.2% per year). Neither was there an increase in the rate of primary endpoint after emergent bradycardia was recorded compared with those without emergent bradycardia. There were 754 cases of emergent AF on treatment (2.2% per year ivabradine vs. 1.5% per year placebo) and 469 in the patients with angina (2.2 vs. 1.5% per year). While outcomes occurred more frequently in patients in whom emergent AF had been recorded, there was no treatment-placebo difference in outcomes, including stroke, and no difference in treatment effect in patients with limiting angina. Both in the overall population as well as in the angina subset, bradycardia was common in ivabradine-treated patients, but did not appear to impact outcomes. Emergent AF was relatively rare and did not appear to have an impact on outcomes relative to placebo. ISRCTN61576291. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Heart rate-lowering efficacy and respiratory safety of ivabradine in patients with obstructive airway disease: a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Majewski, Sebastian; Slomka, Sebastian; Zielinska-Wyderkiewicz, Ewa; Ciebiada, Maciej; Gorski, Pawel

2012-06-01

There is substantial evidence that heart rate (HR) is a powerful predictor of mortality in both normal individuals and in patients with cardiovascular disease. The use of β-adrenoceptor antagonists (β-blockers) has confirmed the importance of lowering elevated HR in a patient's prognosis. However, these agents can have undesirable adverse effects (AEs) and due to the risk of bronchoconstriction are contraindicated in patients with obstructive airway disease. A selective bradycardic agent, without such undesirable effects, could be of therapeutic interest. Ivabradine, a new I(f) inhibitor that acts specifically on the sino-atrial node, is a pure HR-lowering agent. The objective of this study was to assess HR-lowering efficacy and respiratory safety of ivabradine in patients with asthma and chronic obstructive pulmonary disease (COPD). This was a randomized, single-center, double-blind, placebo-controlled, crossover trial. Enrolment began in May 2009, and the last patient completed the study in January 2011. The study was conducted in an ambulatory setting. A total of 40 patients completed the study (20 asthmatic patients and 20 COPD patients). Inclusion criteria were: documented diagnosis of asthma or COPD according to international guidelines, age 18-75 years, and mean HR on Holter ECG recording of ≥60 beats/min. Exclusion criteria included disease exacerbation in a previous month or inability to understand instructions on the study procedures. All patients received ivabradine 7.5 mg twice daily for 5 days and placebo twice daily for 5 days in a crossover manner, in one of the two arms of the study, with at least 2 days of washout between treatments. The main outcome measures included the difference in HR between ivabradine and placebo treatment and change in HR in comparison with baseline. Other evaluated outcomes were differences in the peak expiratory flow rate (PEFR), the daily symptom score, rescue medication consumption, and AEs. Ivabradine produced significantly lower mean HR than placebo in both groups of patients: asthma 67.4 ± 8.38 versus 82.85 ± 11.19 beats/min (p < 0.001) and COPD 69.75 ± 8.9 versus 81.05 ± 9.75 beats/min (p < 0.001). Similar results were observed for the minimal HR as well as for the maximal noted HR. In comparision with baseline, ivabradine significantly reduced HR in both groups of studied patients (all p < 0.05), whereas placebo did not have such an effect. No significant difference, in either the asthma or the COPD group, was found between ivabradine and placebo in morning and evening peak expiratory flow rate, peak expiratory flow diurnal variability, daily symptom scores, and rescue medication usage (all p > 0.05). Both treatments were well tolerated. The incidence of AEs was low and generally similar in both periods of treatment, except for visual symptoms during treatment with ivabradine, which was reported by 5% of the patients. Our study demonstrated that selective HR reduction with ivabradine is effective in patients with asthma and COPD, with no alteration in respiratory function or symptoms over the duration of the study. Ivabradine offers an interesting alternative, as an HR-lowering agent, in patients with respiratory disease and contraindications to β-blockers. Registered at www.clinicaltrials.gov (NCT01365286).

Acute effect of ivabradine on heart rate and myocardial oxygen consumption in dogs with asymptomatic mitral valve degeneration.

PubMed

Pirintr, Prapawadee; Limprasutr, Vudhiporn; Saengklub, Nakkawee; Pavinadol, Parnpradub; Yapao, Napat; Limvanicharat, Natthakarn; Kuecharoen, Hathaisiri; Kijtawornrat, Anusak

2018-05-14

Degenerative mitral valve disease (DMVD) is a common cardiac disease in geriatric dogs characterized by the degeneration of the mitral valve, leading to decreased cardiac output and activation of the sympathetic and renin-angiotensin-aldosterone system. This disease results in an increased resting heart rate (HR) and myocardial oxygen consumption (MVO 2 ). A recent publication demonstrated that dogs with asymptomatic DMVD had a significantly higher HR and systemic blood pressure (BP) than age-matched control dogs. This higher HR will eventually contribute to increased MVO 2 . This study aimed to determine the effects of a single oral dose of ivabradine on the HR, MVO 2 as assessed by the rate-pressure product, and BP in dogs with asymptomatic DMVD. Seven beagles with naturally occurring DMVD were instrumented by the Holter recorder and an oscillometric device to measure electrocardiogram and BP for 24 and 12 h, respectively. Each dog was randomly subjected to receive either placebo or ivabradine (0.5, 1.0 and 2.0 mg/kg). The results revealed that oral administration of ivabradine significantly decreased the HR and rate-pressure product in a dose-dependent manner without adverse effects. The highest dose of 2.0 mg/kg significantly reduced systolic and mean BP. Therefore, the findings imply that a single oral ivabradine administration at a dose of 1.0 mg/kg is suitable for dogs with asymptomatic DMVD to reduce the HR and MVO 2 without marked effects on BP. This may potentially make ivabradine promising for management of an elevated HR in DMVD dogs.

The Role of Ivabradine in the Management of Angina Pectoris.

PubMed

Giavarini, Alessandra; de Silva, Ranil

2016-08-01

Stable angina pectoris affects 2-4 % of the population in Western countries and entails an annual risk of death and nonfatal myocardial infarction of 1-2 % and 3 %, respectively. Heart rate (HR) is linearly related to myocardial oxygen consumption and coronary blood flow, both at rest and during stress. HR reduction is a key target for the prevention of ischemia/angina and is an important mechanism of action of drugs which are recommended as first line therapy for the treatment of angina in clinical guidelines. However, many patients are often unable to tolerate the doses of beta blocker or non-dihydropyridine calcium antagonists required to achieve the desired symptom control. The selective pacemaker current inhibitor ivabradine was developed as a drug for the management of patients with angina pectoris, through its ability to reduce HR specifically. The available data suggest that ivabradine is a well-tolerated and effective anti-anginal agent and it is recommended as a second-line agent for relief of angina in guidelines. However, recent clinical trials of ivabradine have failed to show prognostic benefit and have raised potential concerns about safety. This article will review the available evidence base for the current role of ivabradine in the management of patients with symptomatic angina pectoris in the context of stable coronary artery disease.

The BEAUTIFUL study: randomized trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction - baseline characteristics of the study population.

PubMed

Ferrari, R; Ford, I; Fox, K; Steg, P G; Tendera, M

2008-01-01

Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to evaluate the effects of ivabradine on outcome in such patients receiving optimal medical therapy. This report describes the study population at baseline. BEAUTIFUL is an international, multicentre, randomized, double-blind trial to compare ivabradine with placebo in reducing mortality and cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction <40%). A total of 10,917 patients were randomized. At baseline, their mean age was 65 years, 83% were male, 98% Caucasian, 88% had previous myocardial infarction, 37% had diabetes, and 40% had metabolic syndrome. Mean ejection fraction was 32% and resting heart rate was 71.6 bpm. Concomitant medications included beta-blockers (87%), renin-angiotensin system agents (89%), antithrombotic agents (94%), and lipid-lowering agents (76%). Main results from BEAUTIFUL are expected in 2008, and should show whether ivabradine, on top of optimal medical treatment, reduces mortality and cardiovascular events in this population of high-risk patients. (c) 2007 S. Karger AG, Basel

The effect of ivabradine on functional capacity in patients with chronic obstructive pulmonary disease.

PubMed

Mahmoud, Kareem; Kassem, Hussien Heshmat; Baligh, Essam; ElGameel, Usama; Akl, Yosri; Kandil, Hossam

2016-10-01

Increased sympathetic tone and use of bronchodilators increase heart rate and this may worsen functional capacity in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to look at the short-term effect of the heart rate lowering drug ivabradine on clinical status in COPD patients.We randomised 80 COPD patients with sinus heart rate ≥90 bpm into either taking ivabradine 7.5 mg twice per day or placebo for two weeks. We assessed all patients using the modified Borg scale and 6-minute walk test at baseline and then again 2 weeks after randomisation.There were no significant differences in age, sex, severity of airway obstruction (measured using forceful exhalation), severity of diastolic dysfunction or pulmonary artery systolic pressure between the two groups. The ivabradine group showed significant improvement in 6-minute walk distance (from 192.6±108.8 m at baseline to 285.1±88.9 m at the end of the study) compared with the control group (230.6±68.4 at baseline and 250.4±65.8 m at the end of study) (p<0.001). This improvement in the drug group was associated with significant improvement of dyspnea on modified Borg scale (p=0.007).Lowering heart rate with ivabradine can improve exercise capacity and functional class in COPD patients with resting heart rate >90 bpm. © Royal College of Physicians 2016. All rights reserved.

Advances in the management of heart failure: the role of ivabradine

PubMed Central

Müller-Werdan, Ursula; Stöckl, Georg; Werdan, Karl

2016-01-01

A high resting heart rate (≥70–75 b.p.m.) is a risk factor for patients with heart failure (HF) with reduced ejection fraction (EF), probably in the sense of accelerated atherosclerosis, with an increased morbidity and mortality. Beta-blockers not only reduce heart rate but also have negative inotropic and blood pressure-lowering effects, and therefore, in many patients, they cannot be given in the recommended dose. Ivabradine specifically inhibits the pacemaker current (funny current, If) of the sinoatrial node cells, resulting in therapeutic heart rate lowering without any negative inotropic and blood pressure-lowering effect. According to the European Society of Cardiology guidelines, ivabradine should be considered to reduce the risk of HF hospitalization and cardiovascular death in symptomatic patients with a reduced left ventricular EF ≤35% and sinus rhythm ≥70 b.p.m. despite treatment with an evidence-based dose of beta-blocker or a dose below the recommended dose (recommendation class “IIa” = weight of evidence/opinion is in favor of usefulness/efficacy: “should be considered”; level of evidence “B” = data derived from a single randomized clinical trial or large nonrandomized studies). Using a heart rate cutoff of ≥ 75 b.p.m., as licensed by the European Medicines Agency, treatment with ivabradine 5–7.5 mg b.i.d. reduces cardiovascular mortality by 17%, HF mortality by 39% and HF hospitalization rate by 30%. A high resting heart rate is not only a risk factor in HF with reduced EF but also at least a risk marker in HF with preserved EF, in acute HF and also in special forms of HF. In this review, we discuss the proven role of ivabradine in the validated indication “HF with reduced EF” together with interesting preliminary findings, and the potential role of ivabradine in further, specific forms of HF. PMID:27895488

Development of other microtubule-stabilizer families: the epothilones and their derivatives.

PubMed

Brogdon, Cynthia F; Lee, Francis Y; Canetta, Renzo M

2014-05-01

Chemotherapy is the mainstay of treatment for numerous cancer types, but resistance to chemotherapy remains a major clinical issue and is one of the driving influences underlying the development of new anticancer medications. One of the most important classes of chemotherapy agents is the taxanes, which target the cytoskeleton and spindle apparatus of tumor cells by binding to the microtubules, thereby disrupting key cellular mechanisms, including mitosis. Taxane resistance, however, limits treatment options and creates a major challenge for clinicians. Ongoing research has identified several newer classes of microtubule-targeting chemotherapies that may retain activity despite clinical resistance to taxanes. Among these classes, the epothilones have been studied most extensively in the clinical setting. Like taxanes, epothilones stabilize microtubulin turnover, and they have properties favoring their development as anticancer agents. The most clinically advanced epothilone analog is ixabepilone, which is currently the only approved epothilone derivative. Ixabepilone is indicated for the treatment of metastatic or locally advanced breast cancer in combination with capecitabine after failure of an anthracycline and a taxane, or as monotherapy after failure of an anthracycline, a taxane, and capecitabine. In phase II and III trials, ixabepilone showed efficacy in several patient subgroups and in various stages of breast cancer. Common adverse reactions include peripheral sensory neuropathy and asthenia. This paper will discuss the preclinical and clinical development of epothilones and their derivatives across a variety of cancer types.

Antianginal Efficacy of Ivabradine/Metoprolol Combination in Patients With Stable Angina.

PubMed

Zarifis, John; Kallistratos, Manolis; Katsivas, Apostolos

2016-12-01

Medical treatment is the main clinical strategy for controlling patients with chronic stable angina and improving their quality of life (QoL). Ivabradine treatment on top of metoprolol decreases angina symptoms and improves QoL in patients with stable angina and coronary artery disease (CAD). This is a post hoc analysis (636 CAD patients given ivabradine/metoprolol free combination) of a prospective, noninterventional study that included 2403 patients with CAD and stable angina. Data were recorded at baseline at 1 and 4 months after inclusion. Patient QoL was assessed using the EQ-5D questionnaire. From baseline to study completion; ivabradine administration on top of metoprolol decreased heart rate (HR) from 80.8 ± 9.6 to 64.2 ± 6.2 bpm (P < 0.001). Mean number of angina attacks decreased from 2.0 ± 2.0/wk to 0.2 ± 0.6/wk (P < 0.001), whereas nitroglycerin consumption decreased from 1.4 ± 1.9 times/wk to 0.1 ± 0.4 times/wk (P < 0.001). The percentage of patients in Canadian Cardiovascular Society angina class III to IV decreased from 15.4% to 1.9% (P < 0.001). The improvement of symptoms and angina class led to a significant 14.7-point increase in EQ-5D questionnaire score (P < 0.001). Patients with increased HR showed greater improvement (P = 0.001). Adherence to treatment during the entire trial was high (98%). Ivabradine combined with metoprolol significantly decreased angina symptoms and use of nitroglycerin in patients with stable angina and CAD, leading to improved QoL. The benefits observed with this combination explain the high rate of adherence to treatment. © 2016 Wiley Periodicals, Inc.

Ivabradine in Patients with ST-Elevation Myocardial Infarction Complicated by Cardiogenic Shock: A Preliminary Randomized Prospective Study.

PubMed

Barillà, Francesco; Pannarale, Giuseppe; Torromeo, Concetta; Paravati, Vincenzo; Acconcia, Maria Cristina; Tanzilli, Gaetano; Mangieri, Enrico; Dominici, Tania; Martino, Francesco; Pannitteri, Gaetano; Gaudio, Carlo

2016-10-01

An elevated heart rate (HR) is an independent risk factor for mortality and morbidity in patients with acute heart failure (HF). The purpose of this study was to evaluate the impact of ivabradine, a selective HR-lowering agent, in patients with cardiogenic shock (CS) complicating ST-elevation acute myocardial infarction (AMI). Patients with post-AMI CS were randomized to standard treatment (SDT, 28 patients) or to standard treatment plus ivabradine (I + SDT, 30 patients). In the presence of orotracheal intubation (OTI), ivabradine was administered by nasogastric intubation. HR, BP, New York Heart Association (NYHA) class, NT-proBNP, left ventricular ejection fraction (LVEF) and diastolic function (LVDF) were monitored at specific times after the onset of AMI. The primary (surrogate) end-point was the in-hospital halving of plasma NT-proBNP levels. The secondary end-points were cardiovascular death, hospital re-admission for worsening HF, and clinical and haemodynamic improvement. Treatment groups were statistically similar with regard to age, gender distribution, cardiovascular risk factors, number of diseased vessels and overall treated lesions, AMI site and occurrence of OTI. In-hospital mortality was double in the SDT group in comparison with the I + SDT group (14.3 vs. 6.7 %), but the difference was not statistically significant. HR, BP, NT-proBNP and LVEF favorably changed in both groups, but the change was more relevant in the I + SDT group. LVDF significantly changed only in the I + SDT group (p < 0.01). Patients in the I + SDT group did not experience adverse effects. Ivabradine in CS complicating AMI is safe, is associated with a short-term favourable outcome and can be effectively administered by nasogastric intubation.

Effect of early treatment with ivabradine combined with beta-blockers versus beta-blockers alone in patients hospitalised with heart failure and reduced left ventricular ejection fraction (ETHIC-AHF): A randomised study.

PubMed

Hidalgo, Francisco J; Anguita, Manuel; Castillo, Juan C; Rodríguez, Sara; Pardo, Laura; Durán, Enrique; Sánchez, José J; Ferreiro, Carlos; Pan, Manuel; Mesa, Dolores; Delgado, Mónica; Ruiz, Martín

2016-08-15

To analyse the effect of the early coadministration of ivabradine and beta-blockers (intervention group) versus beta-blockers alone (control group) in patients hospitalised with heart failure and reduced left ventricular ejection fraction (HFrEF). A comparative, randomised study was performed to compare the treatment strategies of beta-blockers alone versus ivabradine and beta-blockers starting 24hours after hospital admission, for acute HF in patients with an left ventricular ejection fraction (EF)<40%, sinus rhythm, and a heart rate (HR)>70bpm. A total of 71 patients were examined, 33 in the intervention group and 38 in the control group. No differences were observed with respect to their baseline characteristics or standard treatment at discharge. HR at 28days (64.3±7.5 vs. 70.3±9.3bpm, p=0.01) and at 4months (60.6±7.5 vs. 67.8±8bpm, p=0.004) after discharge were significantly lower in the intervention group. Significant differences were found with respect to the EF and brain natriuretic peptide levels at 4months. No differences in clinical events (rehospitalisation/death) were reported at 4months. No severe side effects attributable to the early administration of ivabradine were observed. The early coadministration of ivabradine and beta-blockers during hospital admission for acute HFrEF is feasible and safe, and it produces a significant decrease in HR at 28days and at 4months after hospital discharge. It also seemed to improve systolic function and functional and clinical parameters of HF patients at short-term. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ixabepilone in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

ClinicalTrials.gov

2014-05-07

Anaplastic Large Cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma

Ivabradine vs metoprolol in patients with acute inferior wall myocardial infarction-"Expanding arena for ivabradine".

PubMed

Priti, Kumari; Ranwa, Bhanwar L; Gokhroo, Rajendra K; Kishore, Kamal; Bisht, Devendra Singh; Gupta, Sajal

2017-08-01

Atrioventricular (AV) blocks are of concern with the use of beta blockers in inferior wall myocardial infarction (MI). Ivabradine lowers heart rate with a lesser risk of AV blocks. To compare ivabradine with metoprolol in acute inferior wall MI in terms of feasibility, tolerability, and efficacy. It was a prospective double-blind single-center randomized controlled study. Of 1032 patients with acute inferior wall MI, 468 eligible patients were randomized in 1:1 manner to ivabradine (group A) and metoprolol (group B). Intention to treat analysis of 426 patients (group A-232 and group B-232) was performed. The primary endpoint was 30-day incidence of major adverse cardiovascular events including death, reinfarction, complete heart block (CHB), and heart failure. Secondary endpoints included 30 days incidence of recurrent angina, readmission, first- or second-degree AV block, and tachyarrhythmias. Both the drugs decreased the mean heart rate to 62.22±2.95 (group A) vs 62.53±3.59 (group B) beats per minute (P=0.33). Ejection fraction improved in both the groups (5.15±1.93% in group A vs 5.52±2.18% in group B, P=0.065). The two groups did not differ significantly in their primary endpoints in terms of death (group A=1.72% vs group B=1.72%, OR=1.00, 95% CI=0.25-4.05, P=1.00), reinfarction (group A=0.86% vs group B=0.86%, OR=1.00, 95% CI=0.14-7.16, P=1.00), heart failure (group A=4.31% vs group B=2.59%, OR=1.70, 95% CI=0.61-4.75, P=0.31), or CHB (0% vs 2.59%, OR=0.07, 95% CI=0.00-1.34, P=0.08). There were no significant differences in the secondary endpoints of recurrent angina, readmission, and tachyarrhythmias except for more first- and second-degree AV blocks with metoprolol (12.93% vs 2.59%, OR=5.59, 95% CI=2.28-13.72, P=0.0002). Ivabradine is well tolerated and equally effective as metoprolol in acute inferior wall ST elevation myocardial infarction patients for lowering the heart rate with lesser risk of AV blocks. © 2017 John Wiley & Sons Ltd.

Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven't Responded to Therapy

ClinicalTrials.gov

2012-03-14

Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Kidney Cancer; Leukemia; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Ivabradine, a novel heart rate slower: is it a sword of double blades in patients with idiopathic dilated cardiomyopathy?

PubMed

Rayan, Mona; Tawfik, Mazen; Alabd, Ali; Gamal, Amr

2011-08-01

To prospectively assess the safety and efficacy of ivabradine in patients with idiopathic dilated cardiomyopathy. We included 35 patients with idiopathic dilated cardiomyopathy with an ejection fraction (EF) <40% and heart rate >70 beats/min despite optimal medical therapy, according to the international guidelines in this prospective, non-randomized, single-arm, open-label safety study. Ivabradine was used as an add-on therapy to the maximally tolerated b-blocker in an increasing titrated dose till a target dose of 15 mg/day or resting heart rate of 60 beats/min for 3 months. During follow-up period the safety, patient tolerance and efficacy of this drug were assessed. All patients underwent 12-lead resting electrocardiography and Holter monitoring at inclusion and after 3 months. Statistical analysis was accomplished using paired t-test and Pearson correlation analysis. We found a significant reduction in the resting heart rate by a mean of 25.9 ± 9.4%, without a significant change of blood pressure. There was no prolongation of PR, QTc or QRS durations. Ventricular ectopic activity showed significant reduction (p<0.001). There was a significant correlation between the resting heart rate, NYHA and left ventricular ejection fraction (p<0.001 for both). One patient developed photopsia and decompensation was observed in another patient. Ivabradine is a safe and effective drug in reducing resting heart rate, improving NYHA functional class without undesirable effects on conduction parameters or ectopic activity.

Analyzing Health-Related Quality of Life Data to Estimate Parameters for Cost-Effectiveness Models: An Example Using Longitudinal EQ-5D Data from the SHIFT Randomized Controlled Trial.

PubMed

Griffiths, Alison; Paracha, Noman; Davies, Andrew; Branscombe, Neil; Cowie, Martin R; Sculpher, Mark

2017-03-01

The aim of this article is to discuss methods used to analyze health-related quality of life (HRQoL) data from randomized controlled trials (RCTs) for decision analytic models. The analysis presented in this paper was used to provide HRQoL data for the ivabradine health technology assessment (HTA) submission in chronic heart failure. We have used a large, longitudinal EuroQol five-dimension questionnaire (EQ-5D) dataset from the Systolic Heart Failure Treatment with the I f Inhibitor Ivabradine Trial (SHIFT) (clinicaltrials.gov: NCT02441218) to illustrate issues and methods. HRQoL weights (utility values) were estimated from a mixed regression model developed using SHIFT EQ-5D data (n = 5313 patients). The regression model was used to predict HRQoL outcomes according to treatment, patient characteristics, and key clinical outcomes for patients with a heart rate ≥75 bpm. Ivabradine was associated with an HRQoL weight gain of 0.01. HRQoL weights differed according to New York Heart Association (NYHA) class (NYHA I-IV, no hospitalization: standard care 0.82-0.46; ivabradine 0.84-0.47). A reduction in HRQoL weight was associated with hospitalizations within 30 days of an HRQoL assessment visit, with this reduction varying by NYHA class [-0.07 (NYHA I) to -0.21 (NYHA IV)]. The mixed model explained variation in EQ-5D data according to key clinical outcomes and patient characteristics, providing essential information for long-term predictions of patient HRQoL in the cost-effectiveness model. This model was also used to estimate the loss in HRQoL associated with hospitalizations. In SHIFT many hospitalizations did not occur close to EQ-5D visits; hence, any temporary changes in HRQoL associated with such events would not be captured fully in observed RCT evidence, but could be predicted in our cost-effectiveness analysis using the mixed model. Given the large reduction in hospitalizations associated with ivabradine this was an important feature of the analysis. The Servier Research Group.

Peripheral Neuropathy Induced by Microtubule-Targeted Chemotherapies: Insights into Acute Injury and Long-term Recovery.

PubMed

Wozniak, Krystyna M; Vornov, James J; Wu, Ying; Liu, Ying; Carozzi, Valentina A; Rodriguez-Menendez, Virginia; Ballarini, Elisa; Alberti, Paola; Pozzi, Eleonora; Semperboni, Sara; Cook, Brett M; Littlefield, Bruce A; Nomoto, Kenichi; Condon, Krista; Eckley, Sean; DesJardins, Christopher; Wilson, Leslie; Jordan, Mary A; Feinstein, Stuart C; Cavaletti, Guido; Polydefkis, Michael; Slusher, Barbara S

2018-02-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of disability in cancer survivors. CIPN investigations in preclinical model systems have focused on either behaviors or acute changes in nerve conduction velocity (NCV) and amplitude, but greater understanding of the underlying nature of axonal injury and its long-term processes is needed as cancer patients live longer. In this study, we used multiple independent endpoints to systematically characterize CIPN recovery in mice exposed to the antitubulin cancer drugs eribulin, ixabepilone, paclitaxel, or vinorelbine at MTDs. All of the drugs ablated intraepidermal nerve fibers and produced axonopathy, with a secondary disruption in myelin structure within 2 weeks of drug administration. In addition, all of the drugs reduced sensory NCV and amplitude, with greater deficits after paclitaxel and lesser deficits after ixabepilone. These effects correlated with degeneration in dorsal root ganglia (DRG) and sciatic nerve and abundance of Schwann cells. Although most injuries were fully reversible after 3-6 months after administration of eribulin, vinorelbine, and ixabepilone, we observed delayed recovery after paclitaxel that produced a more severe, pervasive, and prolonged neurotoxicity. Compared with other agents, paclitaxel also displayed a unique prolonged exposure in sciatic nerve and DRG. The most sensitive indicator of toxicity was axonopathy and secondary myelin changes accompanied by a reduction in intraepidermal nerve fiber density. Taken together, our findings suggest that intraepidermal nerve fiber density and changes in NCV and amplitude might provide measures of axonal injury to guide clinical practice. Significance: This detailed preclinical study of the long-term effects of widely used antitubulin cancer drugs on the peripheral nervous system may help guide clinical evaluations to improve personalized care in limiting neurotoxicity in cancer survivors. Cancer Res; 78(3); 817-29. ©2017 AACR . ©2017 American Association for Cancer Research.

Structural Basis for Induction of Peripheral Neuropathy by Microtubule-Targeting Cancer Drugs.

PubMed

Smith, Jennifer A; Slusher, Barbara S; Wozniak, Krystyna M; Farah, Mohamed H; Smiyun, Gregoriy; Wilson, Leslie; Feinstein, Stuart; Jordan, Mary Ann

2016-09-01

Peripheral neuropathy is a serious, dose-limiting side effect of cancer treatment with microtubule-targeting drugs. Symptoms present in a "stocking-glove" distribution, with longest nerves affected most acutely, suggesting a length-dependent component to the toxicity. Axonal transport of ATP-producing mitochondria along neuronal microtubules from cell body to synapse is crucial to neuronal function. We compared the effects of the drugs paclitaxel and ixabepilone that bind along the lengths of microtubules and the drugs eribulin and vincristine that bind at microtubule ends, on mitochondrial trafficking in cultured human neuronal SK-N-SH cells and on axonal transport in mouse sciatic nerves. Antiproliferative concentrations of paclitaxel and ixabepilone significantly inhibited the anterograde transport velocity of mitochondria in neuronal cells, whereas eribulin and vincristine inhibited transport only at significantly higher concentrations. Confirming these observations, anterogradely transported amyloid precursor protein accumulated in ligated sciatic nerves of control and eribulin-treated mice, but not in paclitaxel-treated mice, indicating that paclitaxel inhibited anterograde axonal transport, whereas eribulin did not. Electron microscopy of sciatic nerves of paclitaxel-treated mice showed reduced organelle accumulation proximal to the ligation consistent with inhibition of anterograde (kinesin based) transport by paclitaxel. In contrast, none of the drugs significantly affected retrograde (dynein based) transport in neuronal cells or mouse nerves. Collectively, these results suggest that paclitaxel and ixabepilone, which bind along the lengths and stabilize microtubules, inhibit kinesin-based axonal transport, but not dynein-based transport, whereas the microtubule-destabilizing drugs, eribulin and vincristine, which bind preferentially to microtubule ends, have significantly less effect on all microtubule-based axonal transport. Cancer Res; 76(17); 5115-23. ©2016 AACR. ©2016 American Association for Cancer Research.

Effect of Selective Heart Rate Slowing in Heart Failure With Preserved Ejection Fraction.

PubMed

Pal, Nikhil; Sivaswamy, Nadiya; Mahmod, Masliza; Yavari, Arash; Rudd, Amelia; Singh, Satnam; Dawson, Dana K; Francis, Jane M; Dwight, Jeremy S; Watkins, Hugh; Neubauer, Stefan; Frenneaux, Michael; Ashrafian, Houman

2015-11-03

Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality but is currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy in HFpEF. We tested the hypothesis that heart rate reduction improves exercise capacity in HFpEF. We conducted a randomized, crossover study comparing selective heart rate reduction with the If blocker ivabradine at 7.5 mg twice daily versus placebo for 2 weeks each in 22 symptomatic patients with HFpEF who had objective evidence of exercise limitation (peak oxygen consumption at maximal exercise [o2 peak] <80% predicted for age and sex). The result was compared with 22 similarly treated matched asymptomatic hypertensive volunteers. The primary end point was the change in o2 peak. Secondary outcomes included tissue Doppler-derived E/e' at echocardiography, plasma brain natriuretic peptide, and quality-of-life scores. Ivabradine significantly reduced peak heart rate compared with placebo in the HFpEF (107 versus 129 bpm; P<0.0001) and hypertensive (127 versus 145 bpm; P=0.003) cohorts. Ivabradine compared with placebo significantly worsened the change in o2 peak in the HFpEF cohort (-2.1 versus 0.9 mL·kg(-1)·min(-1); P=0.003) and significantly reduced submaximal exercise capacity, as determined by the oxygen uptake efficiency slope. No significant effects on the secondary end points were discernable. Our observations bring into question the value of heart rate reduction with ivabradine for improving symptoms in a HFpEF population characterized by exercise limitation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02354573. © 2015 The Authors.

Paclitaxel, Nab-paclitaxel, or Ixabepilone With or Without Bevacizumab in Treating Patients With Stage IIIC or Stage IV Breast Cancer

ClinicalTrials.gov

2016-11-14

Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; HER2/Neu Positive; Male Breast Carcinoma; Progesterone Receptor Negative; Progesterone Receptor Positive; Recurrent Breast Carcinoma; Stage IIIC Breast Cancer AJCC v6; Stage IV Breast Cancer

Heart rate reduction and longevity in mice.

PubMed

Gent, Sabine; Kleinbongard, Petra; Dammann, Philip; Neuhäuser, Markus; Heusch, Gerd

2015-03-01

Heart rate correlates inversely with life span across all species, including humans. In patients with cardiovascular disease, higher heart rate is associated with increased mortality, and such patients benefit from pharmacological heart rate reduction. However, cause-and-effect relationships between heart rate and longevity, notably in healthy individuals, are not established. We therefore prospectively studied the effects of a life-long pharmacological heart rate reduction on longevity in mice. We hypothesized, that the total number of cardiac cycles is constant, and that a 15% heart rate reduction might translate into a 15% increase in life span. C57BL6/J mice received either placebo or ivabradine at a dose of 50 mg/kg/day in drinking water from 12 weeks to death. Heart rate and body weight were monitored. Autopsy was performed on all non-autolytic cadavers, and parenchymal organs were evaluated macroscopically. Ivabradine reduced heart rate by 14% (median, interquartile range 12-15%) throughout life, and median life span was increased by 6.2% (p = 0.01). Body weight and macroscopic findings were not different between placebo and ivabradine. Life span was not increased to the same extent as heart rate was reduced, but nevertheless significantly prolonged by 6.2%.

New Medications for Heart Failure

PubMed Central

Gordin, Jonathan S.; Fonarow, Gregg C.

2016-01-01

Heart failure is common and results in substantial morbidity and mortality. Current guideline-based therapies for heart failure with reduced ejection fraction, including beta-blockers, angiotensin converting enzyme (ACE) inhibitors, and aldosterone antagonists aim to interrupt deleterious neurohormonal pathways and have shown significant success in reducing morbidity and mortality associated with heart failure. Continued efforts to further improve outcomes in patients with heart failure with reduced ejection fraction have led to the first new-in-class medications approved for heart failure since 2005, ivabradine and sacubitril/valsartan. Ivabradine targets the If channels in the sinoatrial node of the heart, decreasing heart rate. Sacubitril/valsartan combines a neprilysin inhibitor that increases levels of beneficial vasodilatory peptides with an angiotensin receptor antagonist. On a background of previously approved, guideline-directed medical therapies for heart failure, these medications have shown improved clinical outcomes ranging from decreased hospitalizations in a select group of patients to a reduction in all-cause mortality across all pre-specified subgroups. In this review, we will discuss the previously established guideline-directed medical therapies for heart failure with reduced ejection fraction, the translational research that led to the development of these new therapies, and the results from the major clinical trials of ivabradine and sacubitril/valsartan. PMID:27038558

[Heart rate control in chronic heart failure patients received cardiovascular implantable electronic device therapy: effects of optimized medication].

PubMed

Gao, Y; Liang, Y C; Yu, H B; Yan, X L; Xu, B G; Liu, R; Wang, N; Xu, G Q; Wang, Z L

2018-03-24

Objective: To investigate the heart rate control situation of chronic heart failure (CHF) patients who received cardiovascular implantable electronic device (CIED) therapy, and to assess the heart rate control efficacy by optimized medication adjustment. Methods: We performed a perspective study in heart failure with reduced left ventricular ejection fraction (HFrEF) patients who received CIED according to guideline recommendations, patients were enrolled from January 2012 to January 2017. Resting heart rate (RHR) recorded by electrocardiogram after 10 minutes' rest and medication usage within 1 month were recorded at baseline. RHR less than 70 beats per minute (bpm) was regarded as well controlled. β-receptor blockers and (or) ivabradine would be added in patients whose RHR were over 70 bpm. RHR after optimized medication adjustment was recorded during follow-up period. Results: One hundred and fifty patients were included in this study with average RHR (80.6±11.9) bpm. RHR was<70 bpm in 27.3% (41/150) patients at baseline and β-receptor blockers was underused in 80.7% patients (88/109) whose RHR was>70 bpm. The overall RHR decreased to (73.1±10.4) bpm and percent of patients with RHR<70 bpm increased to 70.0% (105/150) after up-titration of β-receptor blockers compared to baseline (χ 2 =52.958, P< 0.001). Ivabradine was added in the rest 45 patients and RHR was<70 bpm in 43 out of 45 patients after ivabradine use. The overall RHR decreased to (67.1±2.7) bpm and percent of RHR<70 bpm significantly increased to 98.7% (148/150) (χ 2 =44.504, P< 0.001 vs. up-titration of β-receptor blockers only). Conclusion: RHR in CHF patients who received CIED therapy is not ideally controlled in this patient cohort, individual up-titration ofβ-receptor blockers and ivabradine use may help to optimize RHR in these patients.

Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer

ClinicalTrials.gov

2018-01-29

Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Review of the If selective channel inhibitor ivabradine in the treatment of chronic stable angina.

PubMed

Prasad, Usha K; Gray, David; Purcell, Henry

2009-02-01

Coronary heart disease is the major cause of morbidity and mortality in industrialized countries, and its prevalence is predicted to grow as the population ages. Current drugs for chronic stable angina (such as beta-blockers, calcium-channel blockers, long- and short-acting nitrates, and potassium-channel activators) are often effective, either as monotherapy or in combination, but side effects and contraindications may limit their use. The "I(f)" (for "funny") channel, discovered in 1979, is expressed mainly in the membrane of pacemaker cells present in the sinus node, the atrioventricular node, the ventricular conduction pathways, and ventricular myocytes. By determining the slope of diastolic depolarization, which in turn controls action potential frequency, it is a key determinant of heart rate and so provides a new therapeutic target for controlling angina symptoms. A new antiangina drug, ivabradine, has been developed and licensed for clinical use. It exclusively reduces the heart rate by selectively blocking the I(f) channel of the sino-atrial node. As clinical trials have shown it to be remarkably well-tolerated, ivabradine offers an alternative for patients who cannot take, or are intolerant of, beta blockade. This review provides an insight into this new agent, its historical background, mechanism of action, and pathophysiologic basis, and provides up-to-date evidence-based information on its optimum use in stable angina.

Ixabepilone in Treating Patients With Advanced Urinary Tract Cancer

ClinicalTrials.gov

2013-01-23

Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

Influences of Ivabradine treatment on serum levels of cardiac biomarkers sST2, GDF-15, suPAR and H-FABP in patients with chronic heart failure.

PubMed

Jirak, Peter; Fejzic, Dzeneta; Paar, Vera; Wernly, Bernhard; Pistulli, Rudin; Rohm, Ilonka; Jung, Christian; Hoppe, Uta C; Schulze, P Christian; Lichtenauer, Michael; Yilmaz, Atilla; Kretzschmar, Daniel

2017-12-14

Chronic heart failure (CHF) represents a major cause of hospitalization and death. Recent evidence shows that novel biomarkers such as soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR) and heart-type fatty acid binding protein (H-FABP) are correlated with inflammatory and ischemic responses in CHF patients. In this study we examined the effects of Ivabradine that inhibited the hyperpolarization-activated cyclic nucleotide-gated channel (HCN channel, also called funny current I f ), thereby leading to selective heart rate reduction and improved myocardial oxygen supply on the cardiac biomarkers sST2, GDF-15, suPAR and H-FABP in 50 CHF patients at the University Hospital of Jena. Patients were divided into three groups based on the etiology of CHF: dilated cardiomyopathy (DCM, n=20), ischemic cardiomyopathy (ICM, n=20) and hypertensive cardiomyopathy (HCM, n=10). The patients were administered Ivabradine (5 mg, bid for 3 months, and 7.5 mg bid for further 3 months). Analyses of cardiovascular biomarkers were performed at baseline as well as at 3- and 6-month follow-ups. At 6-month follow-up, GDF-15 levels were significantly reduced compared to baseline levels (P=0.0215), indicating a reduction in the progress of cardiac remodeling. H-FABP concentration was significantly lower in DCM patients compared to ICM (1.89 vs 3.24 μg/mL) and HCM patients (1.89 vs 3.80 μg/mL), and decreased over the 6-month follow-up (P=0.0151). suPAR median levels remained elevated, implying major ongoing inflammatory processes. As shown by significant decreases in GDF-15 and H-FABP levels, a reduction in ventricular remodeling and sub-clinical ischemia could be assumed. However, markers of hemodynamic stress (sST2) and inflammation (suPAR) showed no change or progression after 6 months of Ivabradine treatment in CHF patients. Further studies are necessary to validate the clinical applicability of these novel cardiovascular biomarkers.

Gene Expression Analysis of Circulating Hormone Refractory Prostate Cancer Micrometastases

DTIC Science & Technology

2008-01-01

Toxicity Grade 3 or 4 neutropenia occurred in 54% and 63% of patients treated with second-line ixabepilone and MP, respectively (Table 3). Febrile ... Neutropenia 22 (54) 10 (33) 26 (63) 10 (63) Febrile neutropenia 2 (5)* 2 (7) 4 (10) — Thrombocytopenia 3 (7) 3 (10) 1 (2) 1 (6) * 1 patient died of...independently predicted improved survival. The most common grade 3/4 toxicity associated with second-line treatment was neutropenia (54% of ixabe- pilone

Safety Communication Tools and Healthcare Professionals' Awareness of Specific Drug Safety Issues in Europe: A Survey Study.

PubMed

de Vries, Sieta T; van der Sar, Maartje J M; Coleman, Anna Marie; Escudero, Yvette; Rodríguez Pascual, Alfonso; Maciá Martínez, Miguel-Ángel; Cupelli, Amelia; Baldelli, Ilaria; Šipić, Ivana; Andrić, Adriana; Michan, Line; Denig, Petra; Mol, Peter G M

2018-07-01

National competent authorities (NCAs) use Direct Healthcare Professional Communications (DHPCs) to communicate new drug safety issues to healthcare professionals (HCPs). More knowledge is needed about the effectiveness of DHPCs and the extent to which they raise awareness of new safety issues among HCPs. The objective was to assess and compare general practitioners' (GPs'), cardiologists', and pharmacists' familiarity with DHPCs as communication tools, their awareness of specific drug safety issues, and the sources through which they had become aware of the specific issues. GPs, cardiologists, and pharmacists from nine European countries (Croatia, Denmark, Ireland, Italy, the Netherlands, Norway, Spain, Sweden, and the UK) completed a web-based survey. The survey was conducted in the context of the Strengthening Collaboration for Operating Pharmacovigilance in Europe (SCOPE) Joint Action. Respondents were asked about their familiarity with DHPCs in general and their awareness of safety issues that had recently been communicated and involved the following drugs: combined hormonal contraceptives, diclofenac, valproate, and ivabradine. Those HCPs who were aware of the specific safety issues were subsequently asked to indicate the source through which they had become aware of them. Differences between professions in familiarity with DHPCs and awareness were tested using a Pearson χ 2  test per country and post hoc Pearson χ 2  tests in the case of statistically significant differences. Of the 3288 included respondents, 54% were GPs, 40% were pharmacists, and 7% were cardiologists. The number of respondents ranged from 67 in Denmark to 916 in Spain. Most respondents (92%) were familiar with DHPCs, with one significant difference between the professions: pharmacists were more familiar than GPs in Italy (99 vs 90%, P = 0.004). GPs' awareness ranged from 96% for the diclofenac issue to 70% for the ivabradine issue. A similar pattern was shown for pharmacists (91% aware of the diclofenac issue to 66% of the ivabradine issue). Cardiologists' awareness ranged from 91% for the ivabradine issue to 34% for the valproate issue. Overall, DHPCs were a common source through which GPs (range: 45% of those aware of the contraceptives issue to 60% of those aware of the valproate issue), cardiologists (range: 33% for the contraceptives issue to 61% for the valproate issue), and pharmacists (range: 41% for the contraceptives issue to 51% for the ivabradine issue) had become aware of the specific safety issues, followed by information on websites or in newsletters. GPs, cardiologists, and pharmacists were to a similar extent (highly) familiar with DHPCs, but they differed in awareness levels of specific safety issues. Cardiologists were less aware of safety issues associated with non-cardiology drugs even if these had cardiovascular safety concerns. This implies that additional strategies may be needed to reach specialists when communicating safety issues regarding drugs outside their therapeutic area but with risks related to their field of specialisation. DHPCs were an important source for the different professions to become aware of specific safety issues, but other sources were also often used. NCAs should consider the use of a range of sources when communicating important safety issues to HCPs.

Nemaline myopathy and heart failure: role of ivabradine; a case report.

PubMed

Sarullo, Filippo M; Vitale, Giuseppe; Di Franco, Antonino; Sarullo, Silvia; Salerno, Ylenia; Vassallo, Laura; Baviera, Emanuela Petrona; Marazia, Stefania; Mandalà, Giorgio; Lanza, Gaetano A

2015-01-19

Nemaline myopathy (NM) is a rare congenital myopathy characterized by muscle weakness, hypotonia and the presence in muscle fibers of inclusions known as nemaline bodies and a wide spectrum of clinical phenotypes, ranging from severe forms with neonatal onset to asymptomatic forms. The adult-onset form is heterogeneous in terms of clinical presentation and disease progression. Cardiac involvement occurs in the minority of cases and little is known about medical management in this subgroup of NM patients. We report a rare case of heart failure (HF) in a patient with adult-onset NM in whom ivabradine proved to be able to dramatically improve the clinical picture. We report a case of a 37-year-old man with adult-onset NM, presenting with weakness and hypotonia of the proximal limb muscles and shoulder girdle, severely limiting daily activities. He developed progressive HF over a period of 6 months while attending a rehabilitation program, with reduced left ventricular ejection fraction (LVEF = 20%), manifested by dyspnea and signs of systemic congestion. The patient was started HF therapy with enalapril, carvedilol, spironolactone and loop diuretics. Target HF doses of these drugs (including carvedilol) were not reached because of symptomatic hypotension causing a high resting heart rate (HR) ≥70 beats per minute (bpm). Further deterioration of the clinical picture occurred with several life-threatening arrhythmic episodes requiring external defibrillation. An implantable cardioverter defibrillator (ICD) was then implanted. Persistent high resting HR was successfully treated with ivabradine with HR lowering from 90 bpm to 55 bpm at 1 month follow up, LVEF rising to 50% at 3 month follow up and to 54% at 2,5 year follow up. To date no more hospitalizations for heart failure occurred. A single hospitalization due to aspiration pneumonia required insertion of a tracheostomy tube to protect airways from further aspiration. At present, the patient is attending a regular rehabilitation program with net improvement in neuromotor control and less limitations in daily activities. HF is a rare feature of NM, but it can negatively influence prognosis. Conventional HF therapy and/or heart transplant are the only reasonable strategy in these patients. Ivabradine is a useful, effective and safe drug for therapy in NM patients with HF and should be considered when resting HR remains high despite beta-blockers' full titration or beta-blockers' underdosing due to intolerance or side effects.

Reduction of resting heart rate with antianginal drugs: review and meta-analysis.

PubMed

Cucherat, Michel; Borer, Jeffrey S

2012-07-01

The benefit of heart rate (HR) reduction in patients with stable coronary artery disease is well demonstrated for symptom prevention and relief, and benefits on outcomes are being actively investigated. We aimed to quantify the reduction in resting HR induced by 5 antianginal drugs frequently used for symptom prevention (diltiazem, verapamil, atenolol, metoprolol, and ivabradine) in stable angina pectoris. We identified studies published between 1966 and 2007 in PubMed, Embase, and the Cochrane database and reviewed the bibliographies to locate additional studies. Eligible studies were double-blind, randomized, placebo-controlled trials in patients with stable angina. Trials were combined using weighted mean difference and fixed-effect model meta-analysis. The main outcome measure was resting HR at the study end. For diltiazem, resting HR reduction versus placebo ranged from -0.08 beats per minute (bpm) [95% confidence interval (CI) -1.5 to +1.4] for 120 mg/d to -8.0 bpm (95% CI, -11.1 to -5.0) with 360 mg/d. For sustained-release diltiazem, there was a reduction in resting HR of -4.5 bpm (95% CI, -6.4 to -2.5), with no dose-response relationship (heterogeneity P = 0.62). Resting HR reductions for the other agents were -3.2 bpm (95% CI, -5.1 to -1.3) for verapamil (with no dose-response relationship, heterogeneity P = 0.87); -19.0 bpm (95% CI, -20.4 to -17.6) for atenolol; -13.2 bpm (95% CI, -14.7 to -11.7) for metoprolol (with greater reductions for 150 mg/d and long-acting 190 mg/d); and between -9.3 bpm (95% CI, -13.8 to -4.8) and -19.6 bpm (95% CI, -23.8 to -15.4) for ivabradine. Ivabradine, atenolol, and metoprolol give similar reductions in resting HR (-10 to -20 bpm), whereas verapamil and diltiazem produce only marginal reductions (<10 bpm).

Curcumin-induced Aurora-A suppression not only causes mitotic defect and cell cycle arrest but also alters chemosensitivity to anticancer drugs.

PubMed

Ke, Ching-Shiun; Liu, Hsiao-Sheng; Yen, Cheng-Hsin; Huang, Guan-Cheng; Cheng, Hung-Chi; Huang, Chi-Ying F; Su, Chun-Li

2014-05-01

Overexpression of oncoprotein Aurora-A increases drug resistance and promotes lung metastasis of breast cancer cells. Curcumin is an active anticancer compound in turmeric and curry. Here we observed that Aurora-A protein and kinase activity were reduced in curcumin-treated human breast chemoresistant nonmetastatic MCF-7 and highly metastatic cancer MDA-MB-231 cells. Curcumin acts in a similar manner to Aurora-A small interfering RNA (siRNA), resulting in monopolar spindle formation, S and G2/M arrest, and cell division reduction. Ectopic Aurora-A extinguished the curcumin effects. The anticancer effects of curcumin were enhanced by Aurora-A siRNA and produced additivity and synergism effects in cell division and monopolar phenotype, respectively. Combination treatment with curcumin overrode the chemoresistance to four Food and Drug Administration (FDA)-approved anticancer drugs (ixabepilone, cisplatin, vinorelbine, or everolimus) in MDA-MB-231 cells, which was characterized by a decrease in cell viability and the occurrence of an additivity or synergy effect. Ectopic expression of Aurora-A attenuated curcumin-enhanced chemosensitivity to these four tested drugs. A similar benefit of curcumin was observed in MCF-7 cells treated with ixabepilone, the primary systemic therapy to patients with invasive breast cancer (stages IIA-IIIB) before surgery. Antagonism effect was observed when MCF-7 cells were treated with curcumin plus cisplatin, vinorelbine or everolimus. Curcumin-induced enhancement in chemosensitivity was paralleled by significant increases (additivity or synergy effect) in apoptosis and cell cycle arrest at S and G2/M phases, the consequences of Aurora-A inhibition. These results suggest that a combination of curcumin with FDA-approved anticancer drugs warrants further assessment with a view to developing a novel clinical treatment for breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... hydrochloride and aminopentamide hydrogen sulfate injection. 522.1222b Section 522.1222b Food and Drugs FOOD AND... hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection. (a) Chemical name... hydrochloride, 10-[3-(dimethylamino) propyl] phenothiazine monohydrochloride, and aminopentamide hydrogen...

21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... hydrochloride and aminopentamide hydrogen sulfate injection. 522.1222b Section 522.1222b Food and Drugs FOOD AND... hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection. (a) Chemical name... hydrochloride, 10-[3-(dimethylamino) propyl] phenothiazine monohydrochloride, and aminopentamide hydrogen...

21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... hydrochloride and aminopentamide hydrogen sulfate injection. 522.1222b Section 522.1222b Food and Drugs FOOD AND... hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection. (a) Chemical name... hydrochloride, 10-[3-(dimethylamino) propyl] phenothiazine monohydrochloride, and aminopentamide hydrogen...

21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... hydrochloride and aminopentamide hydrogen sulfate injection. 522.1222b Section 522.1222b Food and Drugs FOOD AND... hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection. (a) Chemical name... hydrochloride, 10-[3-(dimethylamino) propyl] phenothiazine monohydrochloride, and aminopentamide hydrogen...

Gateways to clinical trials.

PubMed

Bayes, M; Rabasseda, X; Prous, J R

2002-05-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables can be retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, abciximab, acarbose, alefacept, alteplase, amisulpride, amoxicillin trihydrate, apomorphine hydrochloride, aprepitant, argatroban monohydrate, aspirin, atenolol; Betamethasone dipropionate, betamethasone valerate, bicalutamide, bleomycin sulfate; Calcium carbonate, candesartan cilexetil, celecoxib, cetirizine hydrochloride, cisplatin, clarithromycin, clavulanate potassium, clomethiazole edisilate, clopidogrel hydrogensulfate, cyclophosphamide, chorionic gonadotropin (human); Dalteparin sodium, desloratadine, dexamethasone, doxorubicin, DPC-083; Efalizumab, efavirenz, enoxaparin sodium, eprosartan mesilate, etanercept, etoposide, ezetimibe; Faropenem daloxate, fenofibrate, fluocinolone acetonide, flutamide, fluvastatin sodium, follitropin beta, fondaparinux sodium; Gabapentin, glibenclamide, goserelin, granisetron hydrochloride; Haloperidol, hydrochlorothiazide; Imiquimod, interferon beta-1a, irbesartan, iseganan hydrochloride; L-758298, lamivudine, lanoteplase, leflunomide, leuprorelin acetate, loratadine, losartan potassium; Melagatran, metformin hydrochloride, methotrexate, metronidazole, micafungin sodium, mitoxantrone hydrochloride; Nelfinavir mesilate, neutral insulin injection, nizatidine; Olopatadine hydrochloride, omeprazole, ondansetron hydrochloride; Pamidronate sodium, paracetamol, paroxetine hydrochloride, perindopril, pimecrolimus, pioglitazone hydrochloride, piroxicam, pleconaril, pralmorelin, pravastatin sodium, prednisolone, prednisone, propofol; Raloxifene hydrochloride, ranpirnase, remifentanil hydrochloride, risedronate sodium, risperidone, rofecoxib, ropinirole hydrochloride, rosuvastatin calcium; Sevoflurane, sildenafil citrate, simvastatin, somatropin; Tacrolimus, tamoxifen citrate, telmisartan, temozolomide, thiopental sodium, tinzaparin sodium, tirofiban hydrochloride, treosulfan, triamcinolone acetonide; Urokinase; Valsartan, vardenafil, vincristine; Warfarin sodium; Ximelagatran; Zidovudine.

Self-association of analgesics in aqueous solution: micellar properties of dextropropoxyphene hydrochloride and methadone hydrochloride.

PubMed

Attwood, D; Tolley, J A

1980-08-01

The solution properties of several analgesics including dextropropoxyphene hydrochloride, methadone hydrochloride, dextromoramide acid tartrate and dipipanone hydrochloride have been examined using light scattering, conductivity, vapour pressure osmometry and surface tension techniques. A micellar pattern of association was established for dextropropoxyphene hydrochloride and methadone hydrochloride and critical micelle concentrations and aggregation numbers are reported. The hydrophobic contribution to the free energy of micellization of dextropropoxyphene was determined from measurement of the critical micelle concentration in the presence of added electrolyte.

21 CFR 522.883 - Etorphine hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... milliliter of etorphine hydrochloride injection, veterinary, contains 1 mg of etorphine hydrochloride in... use the drug unless diprenorphine hydrochloride injection, veterinary, as provided for in § 522.723, is available for use in reversing the effects of etorphine hydrochloride injection, veterinary. (4...

21 CFR 522.883 - Etorphine hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... milliliter of etorphine hydrochloride injection, veterinary, contains 1 mg of etorphine hydrochloride in... use the drug unless diprenorphine hydrochloride injection, veterinary, as provided for in § 522.723, is available for use in reversing the effects of etorphine hydrochloride injection, veterinary. (4...

[Determination of ephedrine hydrochloride, pseudoephedrine hydrochloride and methylephedrine hydrochloride in maxingshigan decoction by CE].

PubMed

Yu, Li-ping; Wang, Xiao-ke; Luo, Jia-bo

2011-04-01

To establish the method for determination of ephedrine hydrochloride, pseudoephedrine hydrochloride and methylephedrine hydrochloride in maxingshigan decoction by capillary electrophoresis. The separation was performed on a fused silica capillary of 60 cm x 55 microcrpm ID (52 cm of effective length). 60 mmol/L NaB4O7 + 10% (V/V) CH3OH (pH 9.0) was selected as the running buffer. The separation voltage was 12 kV. The samples was injected by gravity (10 s, 15 cm). The detection wavelength was 210 nm and berberine hydrochloride was the internal standard. The linear range of determination for ephedrine hydrochloride, pseudoephedrine hydrochloride and methylephedrine hydrochloride were 20.0-160.0 microg/mL (r = 0.9999), 7.5-60.0 microg/mL (r = 0.9991) and 2.0-10.0 microg/mL (r = 0.9993). The average recoveries were 98.0%, 97.0% and 97.8%, the precisions of the method were 2.31%, 2.21% and 2.00% (n=6), respectively. The method is convenient, rapid and accurate for the quality control of maxingshigan decoction.

Yohimbine hydrochloride as an antagonist to xylazine hydrochloride-ketamine hydrochloride immobilization of white-tailed deer

USGS Publications Warehouse

Mech, L.D.; DelGiudice, G.D.; Karns, P.D.; Seal, U.S.

1985-01-01

Thirteen captive and one free-ranging white-tailed deer (Odocoileus virginianus) were immobilized one to six times each with ketamine hydrochloride and xylazine hydrochloride during winter and spring in northern Minnesota. Administration of 0.09 to 0.53 mg of yohimbine hydrochloride per kg IV after each trial reversed the immobilization. The deer raised their heads within a median time of 2.0 min, stood in 6.0 min and walked away in 9.5 min. No adverse side effects were observed for several weeks following the immobilization.

Cinacalcet hydrochloride (Amgen).

PubMed

Iqbal, Jameel; Zaidi, Mone; Schneider, Adina E

2003-06-01

Amgen Inc and Kirin Brewery Co Ltd, under license from NPS Pharmaceuticals Inc, are developing cinacalcet hydrochloride, the lead compound in a series of calcimimetics, for the potential treatment of primary and secondary hyperparathyroidism. Tecalcet hydrochloride was the first compound from this class to be extensively studied and most of the pharmacological data disclosed is for this compound. Cinacalcet hydrochloride was developed in an effort to improve on the poor pharmacokinetics and metabolism of tecalcet hydrochloride.

Structure-based analysis reveals hydration changes induced by arginine hydrochloride.

PubMed

Nakakido, Makoto; Tanaka, Yoshikazu; Mitsuhori, Mariko; Kudou, Motonori; Ejima, Daisuke; Arakawa, Tsutomu; Tsumoto, Kouhei

2008-10-01

Arginine hydrochloride has been used to suppress protein aggregation during refolding and in various other applications. We investigated the structure of hen egg-white lysozyme (HEL) and solvent molecules in arginine hydrochloride solution by X-ray crystallography. Neither the backbone nor side-chain structure of HEL was altered by the presence of arginine hydrochloride. In addition, no stably bound arginine molecules were observed. The number of hydration water molecules, however, changed with the arginine hydrochloride concentration. We suggest that arginine hydrochloride suppresses protein aggregation by altering the hydration structure and the transient binding of arginine molecules that could not be observed.

Interaction between lidocaine hydrochloride (with and without adrenaline) and various irrigants: A nuclear magnetic resonance analysis

PubMed Central

Vidhya, Nirmal; Karthikeyan, Balasubramanian Saravana; Velmurugan, Natanasabapathy; Abarajithan, Mohan; Nithyanandan, Sivasankaran

2014-01-01

Background: Interaction between local anesthetic solution, lidocaine hydrochloride (with and without adrenaline), and root canal irrigants such as sodium hypochlorite (NaOCl), ethylene diamine tetra-acetic acid (EDTA), and chlorhexidine (CHX) has not been studied earlier. Hence, the purpose of this in vitro study was to evaluate the chemical interaction between 2% lidocaine hydrochloride (with and without adrenaline) and commonly used root canal irrigants, NaOCl, EDTA, and CHX. Materials and Methods: Samples were divided into eight experimental groups: Group I-Lidocaine hydrochloride (with adrenaline)/3% NaOCl, Group II-Lidocaine hydrochloride (with adrenaline)/17% EDTA, Group III- Lidocaine hydrochloride (with adrenaline)/2% CHX, Group IV-Lidocaine hydrochloride (without adrenaline)/3% NaOCl, Group V-Lidocaine hydrochloride (without adrenaline)/17% EDTA, Group VI-Lidocaine hydrochloride (without adrenaline)/2% CHX, and two control groups: Group VII-Lidocaine hydrochloride (with adrenaline)/deionized water and Group VIII-Lidocaine hydrochloride (without adrenaline)/deionized water. The respective solutions of various groups were mixed in equal proportions (1 ml each) and observed for precipitate formation. Chemical composition of the formed precipitate was then analysed by nuclear magnetic resonance spectroscopy (NMR) and confirmed with diazotation test. Results: In groups I and IV, a white precipitate was observed in all the samples on mixing the respective solutions, which showed a color change to reddish brown after 15 minutes. This precipitate was then analysed by NMR spectroscopy and was observed to be 2,6-xylidine, a reported toxic compound. The experimental groups II, III, V, and VI and control groups VII and VIII showed no precipitate formation in any of the respective samples, until 2 hours. Conclusion: Interaction between lidocaine hydrochloride (with and without adrenaline) and NaOCl showed precipitate formation containing 2,6-xylidine, a toxic compound. PMID:25097652

21 CFR 524.1662a - Oxytetracycline hydrochloride and hydrocortisone spray.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Oxytetracycline hydrochloride and hydrocortisone... NEW ANIMAL DRUGS § 524.1662a Oxytetracycline hydrochloride and hydrocortisone spray. (a) Specifications. Each 3-ounce unit of oxytetracycline hydrochloride and hydrocortisone spray contains 300...

21 CFR 524.1662a - Oxytetracycline hydrochloride and hydrocortisone spray.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Oxytetracycline hydrochloride and hydrocortisone... NEW ANIMAL DRUGS § 524.1662a Oxytetracycline hydrochloride and hydrocortisone spray. (a) Specifications. Each 3-ounce unit of oxytetracycline hydrochloride and hydrocortisone spray contains 300...

21 CFR 524.1662a - Oxytetracycline hydrochloride and hydrocortisone spray.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Oxytetracycline hydrochloride and hydrocortisone... NEW ANIMAL DRUGS § 524.1662a Oxytetracycline hydrochloride and hydrocortisone spray. (a) Specifications. Each 3-ounce unit of oxytetracycline hydrochloride and hydrocortisone spray contains 300...

21 CFR 524.1662a - Oxytetracycline hydrochloride and hydrocortisone spray.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride and hydrocortisone... NEW ANIMAL DRUGS § 524.1662a Oxytetracycline hydrochloride and hydrocortisone spray. (a) Specifications. Each 3-ounce unit of oxytetracycline hydrochloride and hydrocortisone spray contains 300...

21 CFR 520.1660b - Oxytetracycline hydrochloride capsules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride capsules. 520.1660b... Oxytetracycline hydrochloride capsules. (a) Specifications. The drug is in capsule form with each capsule containing 125 or 250 milligrams of oxytetracycline hydrochloride. Oxytetracycline is the antibiotic...

Gateways to clinical trials.

PubMed

Tomillero, A; Moral, M A

2009-06-01

(+)-Dapoxetine hydrochloride; Abatacept, Adalimumab, Agalsidase beta, Alemtuzumab, Alglucosidase alfa, Aliskiren fumarate, Ambrisentan, Amlodipine, Aripiprazole, Atrasentan, Azacitidine, Azelnidipine; Belotecan hydrochloride, Bevacizumab, Bilastine, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, CG-100649, Cinacalcet hydrochloride, Clindamycin phosphate/ benzoyl peroxide; Dasatinib, Denosumab, Duloxetine hydrochloride, Dutasteride, Dutasteride/tamsulosin; Ecogramostim, Eculizumab, Eltrombopag olamine, EndoTAG-1, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe; FAHF-2, Fondaparinux sodium; Gefitinib, Golimumab; HEV-239, HSV-TK; Imatinib mesylate, Indium 111 ((111)In) ibritumomab tiuxetan, Influenza vaccine(surface antigen, inactivated, prepared in cell culture), Insulin glargine; Kisspeptin-54; Lidocaine/prilocaine, Lomitapide; Maraviroc, Mirodenafil hydrochloride, MK-8141, MVA-Ag85A; Nilotinib hydrochloride monohydrate; Olmesartan medoxomil; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pitavastatin calcium, Prasugrel; Recombinant human relaxin H2, RHAMM R3 peptide, Rivaroxaban, Rosuvastatin calcium, RRz2; Sagopilone, Salinosporamide A, SB-509, Serlopitant, Sirolimus-eluting stent, Sorafenib, Sunitinib malate; Tadalafil, Temsirolimus, Teriparatide, TG-4010, Tositumomab/iodine (I131) tositumomab; Velusetrag Hydrochloride; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

Development of a Rapid Derivative Spectrophotometric Method for Simultaneous Determination of Acetaminophen, Diphenhydramine and Pseudoephedrine in Tablets

PubMed Central

Souri, Effat; Rahimi, Aghil; Shabani Ravari, Nazanin; Barazandeh Tehrani, Maliheh

2015-01-01

A mixture of acetaminophen, diphenhydramine hydrochloride and pseudoephedrine hydrochloride is used for the symptomatic treatment of common cold. In this study, a derivative spectrophotometric method based on zero-crossing technique was proposed for simultaneous determination of acetaminophen, diphenhydramine hydrochloride and pseudoephedrine hydrochloride. Determination of these drugs was performed using the 1D value of acetaminophen at 281.5 nm, 2D value of diphenhydramine hydrochloride at 226.0 nm and 4D value of pseudoephedrine hydrochloride at 218.0 nm. The analysis method was linear over the range of 5-50, 0.25-4, and 0.5-5 µg/mL for acetaminophen, diphenhydramine hydrochloride and pseudoephedrine hydrochloride, respectively. The within-day and between-day CV and error values for all three compounds were within an acceptable range (CV<2.2% and error<3%). The developed method was used for simultaneous determination of these drugs in pharmaceutical dosage forms and no interference from excipients was observed. PMID:25901150

21 CFR 182.1047 - Glutamic acid hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glutamic acid hydrochloride. 182.1047 Section 182.1047 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1047 Glutamic acid hydrochloride. (a) Product. Glutamic acid hydrochloride. (b...

21 CFR 522.536 - Detomidine hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Detomidine hydrochloride injection. 522.536... § 522.536 Detomidine hydrochloride injection. (a) Specification. Each milliliter of sterile aqueous solution contains 10 milligrams of detomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of...

21 CFR 522.1662b - Oxytetracycline hydrochloride with lidocaine injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride with lidocaine... FORM NEW ANIMAL DRUGS § 522.1662b Oxytetracycline hydrochloride with lidocaine injection. (a) Specifications. The drug contains 50 or 100 milligrams of oxytetracycline hydrochloride and 2 percent lidocaine...

21 CFR 520.1660c - Oxytetracycline hydrochloride tablets/boluses.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride tablets/boluses. 520....1660c Oxytetracycline hydrochloride tablets/boluses. (a) Specifications. Each tablet or bolus contains 250, 500, or 1,000 milligrams of oxytetracycline hydrochloride. (b) Sponsors. For sponsors in § 510...

77 FR 28252 - Oral Dosage Form New Animal Drugs; Change of Sponsor; Griseofulvin Powder; Levamisole...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-14

... Hydrochloride Powder; Oxytetracycline Powder AGENCY: Food and Drug Administration, HHS. ACTION: Final rule..., levamisole hydrochloride soluble powder, and oxytetracycline hydrochloride soluble powder from Teva Animal... Griseofulvin Powder, ANADAs 200-146 and 200-247 for Oxytetracycline Hydrochloride Soluble Powder, and ANADAs...

21 CFR 182.1047 - Glutamic acid hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Glutamic acid hydrochloride. 182.1047 Section 182.1047 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1047 Glutamic acid hydrochloride. (a) Product. Glutamic acid hydrochloride. (b...

[Cetyltrimethylammonium bromide for fluorescence enhancement of anhydrotetracycline hydrochloride and iso-tetracycline].

PubMed

Zha, Jian-peng; Lin, Ying; Yang, Xing-hui; Hou, Hai-ni; Wei, Tie-jun; Chen, Xing-li

2002-06-01

Fluorescence enhancement of anhydrotetracycline hydrochloride and iso-tetracycline has been described. The fluorescence intensities of anhydrotetracycline hydrochloride and iso-tetracycline with cetyltrimethylammonium bromide (CTMAB) enhanced by micellar solution have been examined. It is found that fluorescence enhancement of anhydrotetracycline hydrochloride and iso-tetracycline depends on the concentration of CTMAB and pH of the solution. It can be used to develop sensitive methods for the determination of tetracycline hydrochloride and its decomposition product.

Effects of ambroxol hydrochloride on concentrations of paclitaxel and carboplatin in lung cancer patients at different administration times.

PubMed

Li, J; Yi, W; Jiang, P; Sun, R; Li, T

2016-11-30

Our previous preliminary study revealed a synergistic effect of ambroxol hydrochloride with chemotherapeutic agents such as paclitaxel and carboplatin in lung cancer. However, the optimal conditions such as administration time and drug concentration of ambroxol hydrochloride to achieve the maximum synergistic effect remained unclear. Therefore, concentration changes of the chemotherapy drugs paclitaxel and carboplatin in the sputum were observed after ambroxol hydrochloride administration at different times in order to determine the most effective time frame of ambroxol hydrochloride administration. In this study, 470 cases of non-small cell lung cancer (NSCLC) were divided into different groups with ambroxol hydrochloride administered at different time points prior to chemotherapy, while another 171 cases received no ambroxol hydrochloride prior to chemotherapy. The results showed the concentrations of paclitaxel and carboplatin in sputum of patients treated with ambroxol hydrochloride were significantly higher than those of the control group, suggesting that ambroxol hydrochloride significantly increased the local concentrations of chemotherapeutic agents in lung tissues of NSCLC. Furthermore, the intravenous administration of ambroxol hydrochloride more than 48 hours before chemotherapy showed an optimized schedule and much greater efficacy in increasing drug concentrations than that of the control group. No statistical differences were found in the rates of grade 2 or above myelosuppression between the ambroxol intervention and control groups. Taken together, these results demonstrate that ambroxol hydrochloride administered intravenously more than 48 hours prior to chemotherapy optimally increased the concentrations of paclitaxel and carboplatin in lung tissue without significantly increasing hematologic toxicity.

21 CFR 522.2470 - Tiletamine hydrochloride and zolazepam hydrochloride for injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Tiletamine hydrochloride and zolazepam hydrochloride for injection. 522.2470 Section 522.2470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR...

Study on the binding of procaine hydrochloride to DNA/DNA bases and the effect of CdS nanoparticles on the binding behavior.

PubMed

Ping, Gang; Lv, Gang; Gutmann, Sebastian; Chen, Chen; Zhang, Renyun; Wang, Xuemei

2006-01-01

The interaction between procaine hydrochloride and DNA/DNA bases in the absence and presence of cadmium sulfide (CdS) nanoparticles has been explored in this study by using differential pulse voltammetry, atomic force microscopy (AFM) and so on, which illustrates the different binding behaviors of procaine hydrochloride with different DNA bases. The results clearly indicate that the binding of purines to procaine hydrochloride is stronger than that of pyrimidines and the binding affinity is in the order of G > A > T > C. In addition, it was observed that the presence of CdS nanoparticles could remarkably enhance the probing sensitivity for the interaction between procaine hydrochloride and DNA/DNA bases. Furthermore, AFM study illustrates that procaine hydrochloride can bind to some specific sites of DNA chains, which indicates that procaine hydrochloride may interact with some special sequences of DNA.

21 CFR 524.1484b - Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride, and myristyl-gamma-picolinium...

Code of Federal Regulations, 2010 CFR

2010-04-01

..., tetracaine hydrochloride, and myristyl-gamma-picolinium chloride, topical powder. 524.1484b Section 524.1484b... Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride, and myristyl-gamma-picolinium chloride... hydrochloride and .2 milligram of myristyl-gamma-picolinium chloride in each gram of the product in a special...

Hypercrosslinked poly(styrene-co-divinylbenzene) resin as a specific polymeric adsorbent for purification of berberine hydrochloride from aqueous solutions.

PubMed

Li, Yin; Cao, Ruofan; Wu, Xiaofei; Huang, Jianhan; Deng, Shuguang; Lu, Xiuyang

2013-06-15

A hypercrosslinked poly(styrene-co-divinylbenzene) resin (TEPA) was synthesized and characterized as a specific polymeric adsorbent for concentrating berberine hydrochloride from aqueous solutions. Three organic molecules of different sizes (2-naphthol, berberine hydrochloride, and Congo red) were used as target molecules to elucidate the molecular sieving effect of the TEPA adsorbent. Because the TEPA adsorbent has a pore structure consisting mainly of micropores and mesopores, the adsorption of 2-naphthol from aqueous solutions is very efficient due to the micropore filling effect. The adsorption of berberine hydrochloride mostly takes place in the mesopores as well as macropores, while the adsorption of Congo red mainly occurs in the macropores. The smaller adsorbate molecule (2-naphthol) reaches the adsorption equilibrium much faster than the larger ones (berberine hydrochloride and Congo red). An adsorption breakthrough experiment with an aqueous solution containing 2-naphthol and berberine hydrochloride demonstrated that the TEPA adsorbent could effectively remove 2-naphthol from berberine hydrochloride at 0-107 BV (bed volume, 1 BV=10 ml), and the berberine hydrochloride concentration was increased from 66.7% to 99.4%, suggesting that this polymeric adsorbent is promising for purifying berberine hydrochloride and similar alkaloids from herbal plant extracts. Copyright © 2013 Elsevier Inc. All rights reserved.

Degree of corneal anaesthesia after topical application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle.

PubMed

Little, W B; Jean, G St; Sithole, F; Little, E; Jean, K Yvorchuk-St

2016-06-01

The use of corneal anaesthesia is necessary for a range of clinical purposes. Therefore, we assessed and compared the efficacy of corneal anaesthesia after application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle. The 24 clinically normal cows were allocated into two groups. Cows in group 1 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of sterile saline (0.9% NaCl) with fluorescein in the contralateral eye (control). Group 2 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of 0.5% proparacaine hydrochloride with fluorescein in the contralateral eye (control). In each group, corneal touch threshold was determined by Cochet-Bonnet aesthesiometer for both eyes immediately prior to topical administration of solutions, at 1 min and 5 min after administration of topical solutions and every 5 min thereafter for a total of 75 min. Significant corneal anaesthesia was noted immediately following topical application of both oxybuprocaine and proparacaine as compared with controls, with maximal corneal anaesthesia noted 1 min after administration. Both oxybuprocaine and proparacaine produced significant corneal anaesthesia for the duration of the 75-min study. Neither oxybuprocaine hydrochloride nor proparacaine hydrochloride treatment resulted in visible adverse effects. There are limited data available demonstrating the efficacy and duration of corneal anaesthetic agents in cattle. Both oxybuprocaine hydrochloride and proparacaine hydrochloride should be considered practical options for providing corneal anaesthesia in cattle in a clinical setting. © 2016 Australian Veterinary Association.

Elevated Heart Rate is Associated with Cardiac Denervation in Patients with Heart Failure: A 123-Iodine-MIBG Myocardial Scintigraphy Study.

PubMed

Villacorta, Aline Sterque; Villacorta, Humberto; Souza, Jenne Serrão de; Teixeira, José Antônio Caldas; Muradas, Maria Clara S S S; Alves, Christiane Rodrigues; Precht, Bernardo Campanário; Porto, Pilar; Ubaldo, Letícia; Mesquita, Cláudio Tinoco; Nóbrega, Antônio Cláudio Lucas da

2016-11-01

In the Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial (SHIFT), heart rate (HR) reduction with ivabradine was associated with improved survival and reduced hospitalizations in patients with heart failure (HF). The mechanisms by which elevated HR increases mortality are not fully understood. To assess the relationship of baseline HR with clinical, neurohormonal and cardiac sympathetic activity in patients with chronic HF and elevated HR. Patients with chronic HF who were in sinus rhythm and had resting HR>70 bpm despite optimal medical treatment were included in a randomized, double-blind study comparing ivabradine versus pyridostigmine. This report refers to the baseline data of 16 initial patients. Baseline HR (before randomization to one of the drugs) was assessed, and patients were classified into two groups, with HR below or above mean values. Cardiac sympathetic activity was assessed by 123-iodine-metaiodobenzylguanidine myocardial scintigraphy. Mean HR was 83.5±11.5 bpm (range 72 to 104), and seven (43.7%) patients had HR above the mean. These patients had lower 6-min walk distance (292.3±93 vs 465.2±97.1 m, p=0.0029), higher values of N-Terminal-proBNP (median 708.4 vs 76.1, p=0.035) and lower late heart/mediastinum rate, indicating cardiac denervation (1.48±0.12 vs 1.74±0.09, p<0.001). Elevated resting HR in patients with HF under optimal medical treatment was associated with cardiac denervation, worse functional capacity, and neurohormonal activation. No SHIFT (Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial, ou Estudo do Tratamento da Insuficiência Cardíaca Sistólica com o Inibidor de If Ivabradina), a redução da frequência cardíaca (FC) com ivabradina associou-se com melhor sobrevida e redução das hospitalizações em pacientes com insuficiência cardíaca (IC). Os mecanismos pelos quais a FC elevada aumenta a mortalidade não são totalmente compreendidos. Avaliar a relação da FC basal com atividade clínica, neuro-hormonal e simpática cardíaca em pacientes com IC crônica e FC elevada. Pacientes com IC crônica em ritmo sinusal e FC≥70 apesar de tratamento adequado foram incluídos em um estudo duplo-cego, randomizado, que comparou ivabradina com piridostigmina. Este artigo refere-se a dados basais dos primeiros 16 pacientes. A FC basal (antes da randomização para um dos medicamentos) foi avaliada, e os pacientes classificados em dois grupos, com FC abaixo ou acima dos valores médios. A atividade simpática cardíaca foi avaliada por cintilografia com metaiodobenzilguanidina marcada com iodo 123. A FC média foi 83,5±11,5 bpm (intervalo 72 a 104), e sete pacientes (43.7%) tinham FC acima da média. Esses pacientes apresentaram menor distância percorrida no teste de caminhada de 6 minutos (292,3±93 vs 465,2±97,1 m, p=0,0029), valores mais altos de N-terminal do pró-BNP (mediana 708,4 vs 76,1, p=0,035) e menor relação coração/mediastino tardia, indicando desnervação cardíaca (1,48±0,12 vs 1,74±0,09, p<0,001). A FC de repouso elevada em pacientes com IC em tratamento médico adequado associou-se com desnervação cardíaca, pior capacidade funcional e ativação neuro-hormonal.

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5875 Thiamine hydrochloride. (a) Product. Thiamine hydrochloride. (b) Conditions of use...

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5875 Thiamine hydrochloride. (a) Product. Thiamine hydrochloride. (b) Conditions of use...

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5875 Thiamine hydrochloride. (a) Product. Thiamine hydrochloride. (b) Conditions of use...

21 CFR 522.883 - Etorphine hydrochloride injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... § 522.883 Etorphine hydrochloride injection. (a) Chemical name. 6,7,8,14 - tetrahydro - alpha - methyl - alpha - propyl - 6,14 - endo-ethenooripavine-alpha-methanol hydrochloride. (b) Specifications. Each...

21 CFR 522.883 - Etorphine hydrochloride injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... § 522.883 Etorphine hydrochloride injection. (a) Chemical name. 6,7,8,14 - tetrahydro - alpha - methyl - alpha - propyl - 6,14 - endo-ethenooripavine-alpha-methanol hydrochloride. (b) Specifications. Each...

Glucosamine Hydrochloride

MedlinePlus

... sulfate. People take glucosamine hydrochloride by mouth for osteoarthritis, rheumatoid arthritis, glaucoma, a jaw disorder called temporomandibular ... with chondroitin sulfate, shark cartilage, and camphor for osteoarthritis. Glucosamine hydrochloride is used parenterally and short-term ...

Desipramine hydrochloride overdose

MedlinePlus

... overdose To use the sharing features on this page, please enable JavaScript. Desipramine hydrochloride is a type of medicine called a tricyclic antidepressant. It is taken to relieve symptoms of depression. Desipramine hydrochloride overdose ...

40 CFR 721.1025 - Benzenamine, 4-chloro-2-methyl-; benzenamine, 4-chloro-2-methyl-, hydrochloride; and ben-zenamine...

Code of Federal Regulations, 2010 CFR

2010-07-01

...-; benzenamine, 4-chloro-2-methyl-, hydrochloride; and ben-zenamine, 2-chloro-6-methyl-. 721.1025 Section 721... Benzenamine, 4-chloro-2-methyl-; benzenamine, 4-chloro-2-methyl-, hydrochloride; and ben-zenamine, 2-chloro-6...-, hydrochloride (CAS Number 3165-93-3); and benzenamine, 2-chloro-6-methyl- (CAS Number 87-63-8) are subject to...

Gateways to clinical trials.

PubMed

Bayes, M; Rabasseda, X; Prous, J R

2006-03-01

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131I-labetuzumab; Abacavir sulfate, abatacept, adalimumab, ademetionine, adjuvanted influenza vaccine, alefacept, alemtuzumab, amlodipine, amphotericin B, anakinra, aripiprazole, aspirin, axitinib; Betamethasone dipropionate, bevacizumab, biphasic insulin aspart, bortezomib, bosentan, botulinum toxin type B, BQ-123; Calcium folinate, canertinib dihydrochloride, carboplatin, carmustine, cetirizine hydrochloride, cetuximab, cholecalciferol, ciclesonide, ciclosporin, cinacalcet hydrochloride, cisplatin, clarithromycin, clofazimine, cold-adapted influenza vaccine trivalent, CpG-7909; Darbepoetin alfa, darifenacin hydrobromide, DB-289, desloratadine, Dexamet, dicycloverine hydrochloride, dimethyl fumarate, docetaxel, dolastatin 10, drospirenone, drospirenone/estradiol, duloxetine hydrochloride; Ecogramostim, edotecarin, efaproxiral sodium, enalapril maleate, epoetin beta, epoprostenol sodium, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, estradiol, etanercept; Fluconazole, fludarabine phosphate, fluorouracil; Gefitinib, gemcitabine, Ghrelin (human), glibenclamide, glimepiride, GTI-2040; Haloperidol, human insulin, hydrocortisone probutate; Imatinib mesylate, indisulam, influenza vaccine, inhaled insulin, insulin aspart, insulin glulisine, insulin lispro, irinotecan, ispronicline; Lamivudine, lamivudine/zidovudine/abacavir sulfate, lapatinib, letrozole, levocetirizine, lomustine, lonafarnib, lumiracoxib;Magnesium sulfate, MD-1100, melphalan, metformin hydrochloride, methotrexate, metoclopramide hydrochloride, mitiglinide calcium hydrate, monophosphoryl lipid A, montelukast sodium, motexafin gadolinium, mycophenolate mofetil, mycophenolic acid sodium salt; Nitisinone; Omalizumab, omapatrilat, ONYX-015, oxaliplatin; Paclitaxel, paclitaxel nanoparticles, panitumumab, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pertuzumab, phosphatidylcholine-rich phospholipid mixture, pimecrolimus, pioglitazone hydrochloride, pramlintide acetate, prasterone; QR-333; Ranelic acid distrontium salt, ranolazine, rasagiline mesilate, RFB4(dsFv)-PE38, ribavirin, rifabutin, risperidone, rituximab, rofecoxib, rosiglitazone maleate, rosiglitazone maleate/metformin hydrochloride, rotavirus vaccine; S-236, salmeterol xinafoate, sarizotan hydrochloride, sildenafil, sildenafil citrate, sunitinib malate; Tadalafil, tegaserod maleate, temozolomide, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipifarnib, trabectedin, treprostinil sodium; Vandetanib, vardenafil hydrochloride hydrate, vatalanib succinate, vinflunine, virosome influenza vaccine, voriconazole; Zidovudine. (c) 2006 Prous Science. All rights reserved.

Physical and chemical stability of palonosetron hydrochloride with five common parenteral drugs during simulated Y-site administration.

PubMed

Kupie, Thomas C; Trusley, Craig; Ben, Michel; Trissel, Lawrence A

2008-09-15

The physical and chemical compatibility of palonosetron hydrochloride with atropine sulfate, famotidine, heparin sodium, lidocaine hydrochloride, and potassium chloride during simulated Y-site administration were studied. Test samples were prepared in duplicate by separately mixing 7.5-mL samples of undiluted palonosetron hydrochloride 50 microg/mL with 7.5-mL samples of atropine sulfate 0.4 mg/mL, famotidine 2 mg/mL, undiluted heparin sodium 100 units/mL, lidocaine hydrochloride 10 mg/mL, and potassium chloride 0.1 meq/mL diluted in 5% dextrose in colorless 15-mL borosilicate glass screw-cap culture tubes with polypropylene caps. Physical stability of the admixtures was assessed by visual examination and by measuring turbidity and particle size and content. Chemical stability of atropine sulfate, famotidine, heparin sodium, and lidocaine hydrochloride was assessed by stability-indicating high-performance liquid chromatography. Potassium chloride concentration was determined by indirect potentiometry using a potassiumion selective electrode. All of the samples of palonosetron hydrochloride with the test drugs were initially clear and colorless in normal fluorescent room light and when viewed with a Tyndall beam. Changes in turbidity for the samples were minor throughout the study. Measured particulates of 10 mum or larger were found to be few in number in all samples and remained so throughout the observation period. The admixtures remained colorless throughout the study. No loss of palonosetron hydrochloride occurred with any of the drugs over four hours. Similarly, little or no loss of the other drugs occurred in four hours. Palonosetron hydrochloride is physically and chemically stable with atropine sulfate, famotidine, heparin sodium, lidocaine hydrochloride, and potassium chloride during simulated Y-site administration.

Physical and chemical stability of palonosetron hydrochloride with five opiate agonists during simulated Y-site administration.

PubMed

Trissel, Lawrence A; Trusley, Craig; Ben, Michel; Kupiec, Thomas C

2007-06-01

The physical and chemical compatibility of palonosetron hydrochloride with fentanyl citrate, hydromorphone hydrochloride, meperidine hydrochloride, morphine sulfate, and sufentanil citrate during simulated Y-site administration was studied. Test samples were prepared in triplicate by mixing 7.5-mL samples of undiluted palonosetron 50 microg/mL (of palonosetron) with 7.5-mL samples of fentanyl citrate 50 microg/mL, morphine sulfate 15 mg/mL, hydromorphone hydrochloride 0.5 mg/mL, meperidine hydrochloride 10 mg/mL, and sufentanil citrate 12.5 microg/mL (of sufentanil) per milliliter individually in colorless 15-mL borosilicate glass screw-cap culture tubes with polypropylene caps. Physical stability of the admixtures was assessed by visual examination and by measuring turbidity and particle size and content. Chemical stability was assessed by stability-indicating high-performance liquid chromatography. Evaluations were performed immediately and one and four hours after mixing. All of the admixtures were initially clear and colorless in normal fluorescent room light and when viewed with a high-intensity monodirectional light (Tyndall beam) and were essentially without haze. Changes in turbidity were minor throughout the study. Particulates measuring 10 microm or larger were few in all samples throughout the observation period. The admixtures remained colorless throughout the study. No loss of palonosetron hydrochloride occurred with any of the opiate agonists tested over the four-hour period. Similarly, little or no loss of the opiate agonists occurred over the four-hour period. Palonosetron hydrochloride was physically and chemically stable with fentanyl citrate, hydromorphone hydrochloride, meperidine hydrochloride, morphine sulfate, and sufentanil citrate during simulated Y-site administration.

Facilitatory effect of AC-iontophoresis of lidocaine hydrochloride on the permeability of human enamel and dentine in extracted teeth.

PubMed

Ikeda, Hideharu; Suda, Hideaki

2013-04-01

The objectives of the present study were to quantitatively evaluate chemical permeability through human enamel/dentine using conductometry and to clarify if alternating current (AC) iontophoresis facilitates such permeability. Electrical impedance of different concentrations of lidocaine hydrochloride was measured using a bipolar platinum impedance probe. A quadratic curve closely fitted to the response functions between conductance and lidocaine hydrochloride. For analysis of the passage of lidocaine hydrochloride through human enamel/dentine, eight premolars that were extracted for orthodontic treatment were sectioned at the cemento-enamel junction. The tooth crowns were held between two chambers with a double O-ring. The enamel-side chamber was filled with lidocaine hydrochloride, and the pulp-side chamber was filled with extrapure water. Two platinum plate electrodes were set at the end of each chamber to pass alternating current. A simulated interstitial pulp pressure was applied to the pulp-side chamber. The change in the concentration of lidocaine hydrochloride in the pulp-side chamber was measured every 2min using a platinum recording probe positioned at the centre of the pulp-side chamber. Passive entry without iontophoresis was used as a control. The level of lidocaine hydrochloride that passed through enamel/dentine against the dentinal fluid flow increased with time. Electrical conductance (G, mho) correlated closely to the concentration (x, mmol/L) of lidocaine hydrochloride (G=2.16x(2)+0.0289x+0.000376, r(2)=0.999). Lidocaine hydrochloride can pass through enamel/dentine. Conductometry showed that the level of lidocaine hydrochloride that passed through enamel/dentine was increased by AC iontophoresis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2005-04-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort extract, synthetic human secretin; Taxus, telavancin hydrochloride, telithromycin, temoporfin, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, teriparatide, testosterone gel, TG-1024, tirapazamine, travoprost, travoprost/timolol; Valdecoxib, valganciclovir hydrochloride, voriconazole; Ximelagatran.

p53, Bcl-2 and cox-2 are involved in berberine hydrochloride-induced apoptosis of HeLa229 cells.

PubMed

Wang, Hai-Yan; Yu, Hai-Zhong; Huang, Sheng-Mou; Zheng, Yu-Lan

2016-10-01

The present study aimed to investigate the effects of berberine hydrochloride on the proliferation and apoptosis of HeLa229 human cervical cancer cells. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to examine the cytotoxicity of berberine hydrochloride against HeLa229 cells. The effects of berberine hydrochloride on the apoptosis of HeLa229 cells was detected by immunofluorescence and flow cytometry, and the mRNA expression levels of p53, B‑cell lymphoma 2 (Bcl‑2) and cyclooxygenase‑2 (cox‑2) were analyzed by reverse transcription-quantitative polymerase chain reaction. Berberine hydrochloride inhibited the proliferation of HeLa229 cells in a dose‑dependent manner; minimum cell viability (3.61%) was detected following treatment with 215.164 µmol/l berberine hydrochloride and the half maximal inhibitory concentration value was 42.93 µmol/l following treatment for 72 h. In addition, berberine hydrochloride induced apoptosis in HeLa229 cells in a dose‑ and time‑dependent manner. Berberine hydrochloride upregulated the mRNA expression levels of p53, and downregulated mRNA expression levels of Bcl‑2 and cox‑2, in a dose‑dependent manner. In conclusion, berberine hydrochloride inhibited the proliferation and induced apoptosis of HeLa229 cells, potentially via the upregulation of p53 and the downregulation of Bcl‑2 and cox‑2 mRNA expression levels.

Anti-Inflammatory Effects of Berberine Hydrochloride in an LPS-Induced Murine Model of Mastitis

PubMed Central

Feng, Shibin; Ding, Nana; He, Yanting; Li, Cheng; Li, Manman; Ding, Xuedong; Ding, Hongyan; Li, Jinchun

2018-01-01

Berberine hydrochloride is an isoquinoline type alkaloid extracted from Berberidaceae, Rutaceae, and other plants. Previous reports have shown that berberine hydrochloride has anti-inflammatory properties. However, the underlying molecular mechanisms remain unclear. In this study, a lipopolysaccharide- (LPS-) induced murine model of mastitis was established to explore the anti-inflammatory action of berberine hydrochloride. Sixty mice that had been lactating for 5–7 days were randomly divided into six groups, including control, LPS, three berberine hydrochloride treatment groups (5, 10, and 20 mg/kg), and a dexamethasone (DEX) (5 mg/kg) group. Berberine hydrochloride was administered intraperitoneally 1 h before and 12 h after LPS-induced mastitis, and all mice were sacrificed 24 h after LPS induction. The pathological and histopathological changes of the mammary glands were observed. The concentrations and mRNA expressions of TNF-α, IL-1β, and IL-6 were measured by ELISA and qRT-PCR. The activation of TLR4 and NF-κB signaling pathways was analyzed by Western blot. Results indicated that berberine hydrochloride significantly attenuated neutrophil infiltration and dose-dependently decreased the secretion and mRNA expressions of TNF-α, IL-1β, and IL-6 within a certain range. Furthermore, berberine hydrochloride suppressed LPS-induced TLR4 and NF-κB p65 activation and the phosphorylation of I-κB. Berberine hydrochloride can provide mice robust protection from LPS-induced mastitis, potentially via the TLR4 and NF-κB pathway.

Acute dermal toxicity of guanidine hydrochloride in rabbits. Report for 18 May-1 August 1984

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hiatt, G.F.; Sanso, S.K.; Korte, D.W.

1989-12-01

The acute dermal toxicity of guanidine hydrochloride was evaluated in five male and five female New Zealand White rabbits. Guanidine hydrochloride (2 g/kg) was applied topically to the clipped dorsal skin surface for 24 hours. No compound-related deaths or clinical signs were observed; however, guanidine hydrochloride did produce dermal irritation, necrosis, and eschar formation under conditions of the study.

Analgesic Effect of Intraperitoneal Bupivacaine Hydrochloride After Laparoscopic Sleeve Gastrectomy: a Randomized Clinical Trial.

PubMed

Alamdari, Nasser Malekpour; Bakhtiyari, Mahmood; Gholizadeh, Barmak; Shariati, Catrine

2018-03-01

The indications for sleeve gastrectomy as a primary procedure for the surgical treatment of morbid obesity have increased worldwide. Pain is the most common complaint for patients on the first day after laparoscopic sleeve gastrectomy. There are various methods for decreasing pain after laparoscopic sleeve gastrectomy such as the use of intraperitoneal bupivacaine hydrochloride. This clinical trial was an attempt to discover the effects of intraperitoneal bupivacaine hydrochloride on alleviating postoperative pain after laparoscopic sleeve gastrectomy. In general, 120 patients meeting the inclusion criteria were enrolled. Patients were randomly allocated into two interventions and control groups using a balanced block randomization technique. One group received intraperitoneal bupivacaine hydrochloride (30 cm 3 ), and the other group served as the control one and did not receive bupivacaine hydrochloride. Diclofenac suppository and paracetamol injection were administered to both groups for postoperative pain management. The mean subjective postoperative pain score was significantly decreased in patients who received intraperitoneal bupivacaine hydrochloride within the first 24 h after the surgery; thus, the instillation of bupivacaine hydrochloride was beneficial in managing postoperative pain. The intraoperative peritoneal irrigation of bupivacaine hydrochloride (30 cm 3 , 0.25%) in sleeve gastrectomy patients was safe and effective in reducing postoperative pain, nausea, and vomiting (IRCT2016120329181N4).

Gemcitabine Hydrochloride-Loaded Functionalised Carbon Nanotubes as Potential Carriers for Tumour Targeting

PubMed Central

Das, Shilpee; Desai, Jagruti L.; Thakkar, Hetal P.

2013-01-01

The objective of the present work was to formulate gemcitabine hydrochloride loaded functionalised carbon nanotubes to achieve tumour targeted drug release and thereby reducing gemcitabine hydrochloride toxicity. Multiwalled carbon nanotubes were functionalised using 1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000. Optimised ratio 1:2 of carbon nanotubes:1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000 was taken for loading of gemcitabine hydrochloride. The formulation was evaluated for different parameters. The results showed that maximum drug loading efficiency achieved was 41.59% with an average particle size of 188.7 nm and zeta potential of −10−1 mV. Scanning electron microscopy and transmission electron microscopy images confirmed the tubular structure of the formulation. The carbon nanotubes were able to release gemcitabine hydrochloride faster in acidic pH than at neutral pH indicating its potential for tumour targeting. Gemcitabine hydrochloride release from carbon nanotubes was found to follow Korsmeyer-Peppas kinetic model with non-Fickian diffusion pattern. Cytotoxic activity of formulation on A549 cells was found to be higher in comparison to free gemcitabine hydrochloride. Stability studies indicated that lyophilised samples of the formulation were more stable for 3 months under refrigerated condition than at room temperature. Thus carbon nanotubes can be promising carrier for the anticancer drug gemcitabine hydrochloride. PMID:24591746

Spectrophotometric determination of meclizine hydrochloride and pyridoxine hydrochloride in laboratory prepared mixtures and in their pharmaceutical preparation

NASA Astrophysics Data System (ADS)

Ibrahim, Maha M.; Elzanfaly, Eman S.; El-Zeiny, Mohamed B.; Ramadan, Nesreen K.; Kelani, Khadiga M.

2017-05-01

In this paper, three rapid, simple, accurate and precise spectrophotometric methods were developed for the determination of meclizine hydrochloride in the presence of pyridoxine hydrochloride without previous separation. The methods under study are dual wavelength (DWL), ratio difference (RD) and continuous wavelet transform (CWT). On the other hand, pyridoxine hydrochloride (PYH) was determined directly at 291 nm. The methods obey Beer's law in the range of (5-50 μg/mL) for both compounds. All the methods were validated according to the ICH guidelines where the accuracy was found to be 98.29, 99.59, 100.42 and 100.62% for DWL, RD, CWT and PYH; respectively. Moreover the precision of the methods were calculated in terms of %RSD and it was found to be 0.545, 0.372, 1.287 and 0.759 for DWL, RD,CWT and PYH; respectively. The selectivity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard addition technique. So, they can be used for the routine analysis of pyridoxine hydrochloride and meclizine hydrochloride in quality-control laboratories.

Stability of methadone hydrochloride in 0.9% sodium chloride injection in single-dose plastic containers.

PubMed

Denson, D D; Crews, J C; Grummich, K W; Stirm, E J; Sue, C A

1991-03-01

The stability of methadone hydrochloride in 0.9% sodium chloride injection in flexible polyvinyl chloride containers was studied. Commercially available methadone hydrochloride 20 mg/mL and 25-mL single-dose bags of 0.9% sodium chloride injection were used. Six samples each were prepared at methadone hydrochloride concentrations of 1, 2, and 5 mg/mL. The solutions were stored at room temperature and were not protected from light. Immediately after preparation and after two, three, and four weeks of storage, each of the 18 samples was divided into three aliquots, each of which was analyzed in duplicate for methadone hydrochloride concentration by gas chromatography. There was less than 10% change in methadone hydrochloride concentration in any sample throughout the four-week study period. Methadone hydrochloride at concentrations of 1, 2, and 5 mg/mL prepared in commercially available flexible polyvinyl chloride containers of 0.9% sodium chloride injection and stored at room temperature without deliberate protection from light is stable for at least four weeks.

Spectrophotometric determination of dopamine hydrochloride in pharmaceutical, banana, urine and serum samples by potassium ferricyanide-Fe(III).

PubMed

Guo, Li; Zhang, Yan; Li, Quanmin

2009-12-01

In the present work, we developed a simple, sensitive and inexpensive method to determine dopamine hydrochloride using potassium ferricyanide-Fe(III) by spectrophotometry. The results show that Fe(III) is deoxidized to Fe(II) by dopamine hydrochloride at pH 4.0, and then Fe(II) reacts with potassium ferricyanide to form a soluble prussian blue (KFe(III)[Fe(II)(CN)6]). The absorbance of this product was monitored over time using a spectrophotometer at an absorption maximum of 735 nm, and the amount of dopamine hydrochloride could be calculated based on the absorbance. A good linear relationship of the concentration of dopamine hydrochloride versus absorbance was observed, and a linear regression equation of A = 0.022 + 0.16921C (microg mL(-1)) was obtained. Moreover, the apparent molar absorption coefficient for the indirect determination of dopamine hydrochloride was 3.2 x 10(4) L mol(-1) cm(-1). This described method has been used to determine dopamine hydrochloride in pharmaceutical, banana, urine and serum samples with satisfactory results.

77 FR 35691 - Notice of Withdrawal of Certain Unapproved Abbreviated New Drug Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-14

... Tripelennamine hydrochloride. 85419 Quinidine sulfate. 85439 Butalbital; aspirin; phenacetin; caffeine. 85442.... 86286 Butalbital; aspirin; phenacetin; caffeine. 86288 Amitriptyline hydrochloride. 86316 Orphenadrine...; aspirin; phenacetin; caffeine. 86327 Trifluoperazine hydrochloride. 86334 Hydrocortisone. [[Page 35697...

Simultaneous HPLC analysis of pseudophedrine hydrochloride, codeine phosphate, and triprolidine hydrochloride in liquid dosage forms.

PubMed

Manassra, Adnan; Khamis, Mustafa; El-Dakiky, Magdy; Abdel-Qader, Zuhair; Al-Rimawi, Fuad

2010-03-11

An HPLC method using UV detection is proposed for the simultaneous determination of pseudophedrine hydrochloride, codeine phosphate, and triprolidine hydrochloride in liquid formulation. C18 column (250mmx4.0mm) is used as the stationary phase with a mixture of methanol:acetate buffer:acetonitrile (85:5:10, v/v) as the mobile phase. The factors affecting column separation of the analytes were studied. The calibration graphs exhibited a linear concentration range of 0.06-1.0mg/ml for pseudophedrine hydrochloride, 0.02-1.0mg/ml for codeine phosphate, and 0.0025-1.0mg/ml for triprolidine hydrochloride for a sample size of 5microl with correlation coefficients of better than 0.999 for all active ingredients studied. The results demonstrate that this method is reliable, reproducible and suitable for routine use with analysis time of less than 4min. Copyright 2009 Elsevier B.V. All rights reserved.

Stability of tramadol with three 5-HT3 receptor antagonists in polyolefin bags for patient-controlled delivery systems.

PubMed

Chen, Fu-Chao; Zhu, Jun; Li, Bin; Yuan, Fang-Jun; Wang, Lin-Hai

2016-01-01

Mixing 5-hydroxytryptamine-3 (5-HT3) receptor antagonists with patient-controlled analgesia (PCA) solutions of tramadol has been shown to decrease the incidence of nausea and vomiting associated with the use of tramadol PCA for postoperative pain. However, such mixtures are not commercially available, and the stability of the drug combinations has not been duly studied. The study aimed to evaluate the stability of tramadol with three 5-HT3 receptor antagonists in 0.9% sodium chloride injection for PCA administration. Test samples were prepared by adding 1,000 mg tramadol hydrochloride, 8 mg ondansetron hydrochloride, and 6 mg granisetron hydrochloride or 5 mg tropisetron hydrochloride to 100 mL of 0.9% sodium chloride injection in polyolefin bags. The samples were prepared in triplicates, stored at either 25°C or 4°C for 14 days, and assessed using the following compatibility parameters: precipitation, cloudiness, discoloration, and pH. Chemical stability was also determined using a validated high-pressure liquid chromatography method. All of the mixtures were clear and colorless throughout the initial observation period. No change in the concentration of tramadol hydrochloride occurred with any of the 5-HT3 receptor antagonists during the 14 days. Similarly, little or no loss of the 5-HT3 receptor antagonists occurred over the 14-day period. Our results suggest that mixtures of tramadol hydrochloride, ondansetron hydrochloride, granisetron hydrochloride, or tropisetron hydrochloride in 0.9% sodium chloride injection were physically and chemically stable for 14 days when stored in polyolefin bags at both 4°C and 25°C.

76 FR 11790 - Drugs for Human Use; Drug Efficacy Study Implementation; Oral Prescription Drugs Offered for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-03

... (containing promethazine hydrochloride, ipecac fluidextract, potassium guaiacolsulfonate, citric acid, sodium... promethazine hydrochloride, ipecac fluidextract, potassium guaiacolsulfonate, citric acid, sodium citrate, and... promethazine hydrochloride, ipecac fluidextract, potassium guaiacolsulfonate, citric acid, sodium citrate...

Postpartum immobilization of adult female moose using xylazine, ketamine and yohimbine hydrochlorides.

PubMed

Garner, D L; Addison, E M

1994-01-01

Twenty-two free-ranging adult female moose (Alces alces) were immobilized with a 1:4 mixture of xylazine hydrochloride (XH) and ketamine hydrochloride (KH). Mean (SD) dosages/animal for XH and KH were 419 (148) and 1565 (433) mg, respectively. Mean (SD) induction time was 18.4 (9.7) minutes. Reversal with yohimbine hydrochloride using a mean dosage of 83 mg/animal resulted in a mean (SD) recovery time of 22.8 (28.5) minutes.

Gateways to clinical trials.

PubMed

Bayes, M; Rabasseda, X; Prous, J R

2006-01-01

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:(R)-Flurbiprofen, 90Yttrium-DOTA-huJ591; ABT-510, ACP-103, Ad5-FGF4, adalimumab, ademetionine, AG-7352, alemtuzumab, Amb a 1 ISS-DNA, anakinra, apaziquone, aprepitant, aripiprazole, atazanavir sulfate; BAL-8557, bevacizumab, BMS-188797, bortezomib, bosentan, brivudine; Calcipotriol/betamethasone dipropionate, cannabidiol, caspofungin acetate, catumaxomab, CERE-120, cetuximab, ciclesonide, cilomilast, cizolirtine citrate, Cypher, cystemustine; Dalbavancin, darifenacin hydrobromide, dasatinib, deferasirox, denosumab, desmoteplase, dihydrexidine, dimethyl fumarate, dutasteride, DW-166HC; Eculizumab, enfuvirtide, entecavir, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, eszopiclone, etoricoxib, everolimus; Fallypride, febuxostat, fenretinide, fesoterodine, fingolimod hydrochloride; Gabapentin enacarbil, gefitinib; hMaxi-K, human papillomavirus vaccine, HYAL-CT1101; Imatinib mesylate, indiplon, inolimomab, ISAtx-247; J591; Lacosamide, landiolol, lasofoxifene tartrate, lestaurtinib, lidocaine/prilocaine, linezolid, lixivaptan, lonafarnib, lopinavir, lopinavir/ritonavir, lumiracoxib; Natalizumab, nesiritide; OC-108, omalizumab, onercept, OSC; Palifermin, palonosetron hydrochloride, parathyroid hormone (human recombinant), parecoxib sodium, PD-MAGE-3 vaccine, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pelitinib, pitavastatin calcium, plerixafor hydrochloride, posaconazole, prasterone sulfate, pregabalin; Ramelteon, ranelic acid distrontium salt, rasburicase, rosuvastatin calcium, rotigotine, RSD-1235, rufinamide, rupatadine fumarate; Sarizotan hydrochloride, SHL-749, sirolimus-eluting stent, solifenacin succinate, sunitinib malate; Tadalafil, talampanel, tasidotin hydrochloride, Taxus, tegaserod maleate, telavancin hydrochloride, tenofovir disoproxil fumarate, tiotropium bromide, tocilizumab, tositumomab, treprostinil sodium, tridolgosir hydrochloride, TTS-CD3; Ularitide; Valdecoxib, Val-Tyr sardine peptidase, vardenafil hydrochloride hydrate, voriconazole; Yttrium (90Y) edotreotide, Yttrium 90 (90Y) ibritumomab tiuxetan; Zileuton, zucapsaicin.

Stability of tramadol with three 5-HT3 receptor antagonists in polyolefin bags for patient-controlled delivery systems

PubMed Central

Chen, Fu-chao; Zhu, Jun; Li, Bin; Yuan, Fang-jun; Wang, Lin-hai

2016-01-01

Background Mixing 5-hydroxytryptamine-3 (5-HT3) receptor antagonists with patient-controlled analgesia (PCA) solutions of tramadol has been shown to decrease the incidence of nausea and vomiting associated with the use of tramadol PCA for postoperative pain. However, such mixtures are not commercially available, and the stability of the drug combinations has not been duly studied. The study aimed to evaluate the stability of tramadol with three 5-HT3 receptor antagonists in 0.9% sodium chloride injection for PCA administration. Materials and methods Test samples were prepared by adding 1,000 mg tramadol hydrochloride, 8 mg ondansetron hydrochloride, and 6 mg granisetron hydrochloride or 5 mg tropisetron hydrochloride to 100 mL of 0.9% sodium chloride injection in polyolefin bags. The samples were prepared in triplicates, stored at either 25°C or 4°C for 14 days, and assessed using the following compatibility parameters: precipitation, cloudiness, discoloration, and pH. Chemical stability was also determined using a validated high-pressure liquid chromatography method. Results All of the mixtures were clear and colorless throughout the initial observation period. No change in the concentration of tramadol hydrochloride occurred with any of the 5-HT3 receptor antagonists during the 14 days. Similarly, little or no loss of the 5-HT3 receptor antagonists occurred over the 14-day period. Conclusion Our results suggest that mixtures of tramadol hydrochloride, ondansetron hydrochloride, granisetron hydrochloride, or tropisetron hydrochloride in 0.9% sodium chloride injection were physically and chemically stable for 14 days when stored in polyolefin bags at both 4°C and 25°C. PMID:27350741

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Ethylisobutrazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 50...

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Triflupromazine hydrochloride tablets. 520.2582 Section 520.2582 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Triflupromazine hydrochloride tablets. (a) Specifications. Each tablet contains either 10 milligrams or 25...

76 FR 53907 - Determination That TALWIN COMPOUND (Aspirin; Pentazocine Hydrochloride) Tablets, 325 Milligrams...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

...] Determination That TALWIN COMPOUND (Aspirin; Pentazocine Hydrochloride) Tablets, 325 Milligrams; Equivalent to... determined that TALWIN COMPOUND (aspirin; pentazocine hydrochloride (HCl)) tablets, 325 milligrams (mg... determination will allow FDA to approve abbreviated new drug applications (ANDAs) for aspirin; pentazocine HCl...

Ameliorative Effect of Chronic Supplementation of Protocatechuic Acid Alone and in Combination with Ascorbic Acid in Aniline Hydrochloride Induced Spleen Toxicity in Rats.

PubMed

Khairnar, Upasana; Upaganlawar, Aman; Upasani, Chandrashekhar

2016-01-01

Background. Present study was designed to evaluate the protective effects of protocatechuic acid alone and in combination with ascorbic acid in aniline hydrochloride induced spleen toxicity in rats. Materials and Methods. Male Wistar rats of either sex (200-250 g) were used and divided into different groups. Spleen toxicity was induced by aniline hydrochloride (100 ppm) in drinking water for a period of 28 days. Treatment group received protocatechuic acid (40 mg/kg/day, p.o.), ascorbic acid (40 mg/kg/day, p.o.), and combination of protocatechuic acid (20 mg/kg/day, p.o.) and ascorbic acid (20 mg/kg/day, p.o.) followed by aniline hydrochloride. At the end of treatment period serum and tissue parameters were evaluated. Result. Rats supplemented with aniline hydrochloride showed a significant alteration in body weight, spleen weight, feed consumption, water intake, hematological parameters (haemoglobin content, red blood cells, white blood cells, and total iron content), tissue parameters (lipid peroxidation, reduced glutathione, and nitric oxide content), and membrane bound phosphatase (ATPase) compared to control group. Histopathology of aniline hydrochloride induced spleen showed significant damage compared to control rats. Treatment with protocatechuic acid along with ascorbic acid showed better protection as compared to protocatechuic acid or ascorbic acid alone in aniline hydrochloride induced spleen toxicity. Conclusion. Treatment with protocatechuic acid and ascorbic acid in combination showed significant protection in aniline hydrochloride induced splenic toxicity in rats.

Development and validation of an HPLC method for tetracycline-related USP monographs.

PubMed

Hussien, Emad M

2014-09-01

A novel reversed-phase HPLC method was developed and validated for the assay of tetracycline hydrochloride and the limit of 4-epianhydrotetracycline hydrochloride impurity in tetracycline hydrochloride commercial bulk and pharmaceutical products. The method employed L1 (3 µm, 150 × 4.6 mm) columns, a mobile phase of 0.1% phosphoric acid and acetonitrile at a flow rate of 1.0 mL/min, and detection at 280 nm. The separation was performed in HPLC gradient mode. Forced degradation studies showed that tetracycline eluted as a spectrally pure peak and was well resolved from its degradation products. The fast degradation of tetracycline hydrochloride and 4-epianhydrotetracycline hydrochloride in solution was retarded by controlling the autosampler temperature at 4 °C and using 0.1% H3 PO4 as diluent. The robustness of the method was tested starting with the maximum variations allowed in the US Pharmacopeia (USP) general chapter Chromatography <621>. The method was linear over the range 80-120% of the assay concentration (0.1 mg/mL) for tetracycline hydrochloride and 50-150% of the acceptance criteria specified in the individual USP monographs for 4-epianhydrotetracycline hydrochloride. The limit of quantification for 4-epianhydrotetracycline hydrochloride was 0.1 µg/mL, 20 times lower than the acceptance criteria. The method was specific, precise, accurate and robust. Copyright © 2014 John Wiley & Sons, Ltd.

78 FR 16685 - Impax Laboratories, Inc.; Withdrawal of Approval of Bupropion Hydrochloride Extended-Release...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-18

...] Impax Laboratories, Inc.; Withdrawal of Approval of Bupropion Hydrochloride Extended-Release Tablets... Administration (FDA) is withdrawing approval of Bupropion Hydrochloride (HCl) Extended-Release Tablets, 300 Milligrams (mg) (Bupropion HCl Extended-Release Tablets 300 mg), under Abbreviated New Drug Application (ANDA...

21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... an aqueous solution which contains in each fluid ounce 0.36 gram of levamisole hydrochloride and piperazine dihydrochloride equivalent to 3.98 grams of piperazine base. (2) The drug is a soluble powder which when reconstituted with water contains in each fluid ounce 0.45 gram of levamisole hydrochloride...

21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... an aqueous solution which contains in each fluid ounce 0.36 gram of levamisole hydrochloride and piperazine dihydrochloride equivalent to 3.98 grams of piperazine base. (2) The drug is a soluble powder which when reconstituted with water contains in each fluid ounce 0.45 gram of levamisole hydrochloride...

21 CFR 520.1242c - Levamisole hydrochloride and piperazine dihydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... an aqueous solution which contains in each fluid ounce 0.36 gram of levamisole hydrochloride and piperazine dihydrochloride equivalent to 3.98 grams of piperazine base. (2) The drug is a soluble powder which when reconstituted with water contains in each fluid ounce 0.45 gram of levamisole hydrochloride...

21 CFR 520.2345h - Tetracycline hydrochloride, sodium novobiocin, and prednisolone tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... prednisolone tablets. 520.2345h Section 520.2345h Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... ANIMAL DRUGS § 520.2345h Tetracycline hydrochloride, sodium novobiocin, and prednisolone tablets. (a) Specifications. Each tablet contains the equivalent of 60 milligrams of tetracycline hydrochloride, 60 milligrams...

21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms. ...

21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or injectable...

In-Silico Analysis of Amotosalen Hydrochloride Binding to CD-61 of Platelets.

PubMed

Chaudhary, Hammad Tufail

2016-11-01

To determine the docking of Amotosalen hydrochloride (AH) at CD-61 of platelets, and to suggest the cause of bleeding in AH treated platelets transfusion. Descriptive study. Medical College, Taif University, Taif, Saudi Arabia, from October 2014 to May 2015. The study was carried out in-silico. PDB (protein data bank) code of Tirofiban bound to CD-61 was 2vdm. CD-61 was docked with Tirofiban using online docking tools, i.e. Patchdock and Firedock. Then, Amotosalen hydrochloride and CD-61 were also docked. Best docking poses to active sites of 2vdm were found. Ligplot of interactions of ligands and CD-61 were obtained. Then comparison of hydrogen bonds, hydrogen bond lengths, and hydrophobic bonds of 2vdm molecule and best poses of docking results were done. Patchdock and Firedock results of best poses were also analysed using SPSS version 16. More amino acids were involved in hydrogen and hydrophobic bonds in Patchdock and Firedock docking of Amotosalen hydrochloride with CD-61 than Patchdock and Firedock docking of CD-61 with Tirofiban. The binding energy was more in latter than former. Amotosalen hydrochloride binds to the active site of CD-61 with weaker binding force. Haemorrhage seen in Amotosalen hydrochloride-treated platelets might be due to binding of Amotosalen hydrochloride to CD-61.

Development and evaluation of a novel modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride as model drugs.

PubMed

Zeeshan, Farrukh; Bukhari, Nadeem Irfan

2010-06-01

Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine were prepared using extrusion-spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand, the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover, the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion, modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully developed and evaluated.

21 CFR 520.1263a - Lincomycin hydrochloride monohydrate tablets and sirup.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Lincomycin hydrochloride monohydrate tablets and sirup. 520.1263a Section 520.1263a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1263a Lincomycin hydrochloride monohydrate tablets and sirup. (a) Specifications. The sirup...

Effects of metomindate hydrochloride and tricaine methanesulfonate on the short term cortisol response in channel catfish

USDA-ARS?s Scientific Manuscript database

The effects of metomidate hydrochloride and tricaine methanesulfonate (MS-222) on cortisol stress response of channel catfish, Ictalurus punctatus, were examined during 10 minutes of sedation. Channel catfish were assigned to three treatments: 1. Metomidate hydrochloride (12.5 mg/L), 2. MS-222 (100...

78 FR 38053 - Determination That OPANA ER (Oxymorphone Hydrochloride) Drug Products Covered by New Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-25

...] Determination That OPANA ER (Oxymorphone Hydrochloride) Drug Products Covered by New Drug Application 21-610... (oxymorphone hydrochloride (HCl)) Extended-Release Tablet products approved under new drug application (NDA) 21... refer to these drug products, and it will allow FDA to continue to approve ANDAs for oxymorphone HCl...

Potential bacterial contamination of eyedrops used for tonometry.

PubMed

Palmberg, R; Gutierrez, Y S; Miller, D; Feuer, W J; Anderson, D R

1994-05-15

We compared the potential for bacterial contamination of a proparacaine hydrochloride solution preserved with benzalkonium chloride, which is used with fluorescein paper for tonometry, to that of a fluorescein-benoxinate hydrochloride combination solution preserved with chlorobutanol. We contaminated bottles of each solution with Pseudomonas aeruginosa or Staphylococcus aureus (10(7) organisms per milliliter of eyedrop solution). From the fluorescein-benoxinate hydrochloride solution, Staphylococcus organisms were cultured in declining numbers over time, with a half-life of nine seconds, and no Staphylococcus organisms were recovered after five minutes. Pseudomonas organisms disappeared from this solution within 15 seconds. Neither species was viable after 15 seconds in the proparacaine hydrochloride solution. Additionally, we cultured 12 bottles of fluorescein-benoxinate hydrochloride and 15 bottles of proparacaine hydrochloride that had been in use in the clinic for one month. No organisms were recovered from a drop dispensed from any bottle or from the tips, caps, rims, or solution from within any bottle, except that five colonies of Staphylococcus grew from the external rim of one bottle. We conclude that both solutions sterilize themselves rapidly and effectively. Either may be used safely for tonometry.

Solid-state and solution /sup 13/C NMR in the conformational analysis of methadone-hydrochloride and related narcotic analgesics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sumner, S.C.J.

1986-01-01

Solid state and solution /sup 13/C NMR have been used to study the conformations of the racemic mixtures and single enantiomers of methadone hydrochloride, alpha and beta methadol hydrochloride, and alpha and beta acetylmethadol hydrochloride. The NMR spectra acquired for the compounds as solids, and in polar and nonpolar solvents are compared, in order to determine the conformation of the molecules in solution. To determine the reliability of assigning solution conformations by comparing solution and solid state chemical shift data, three bond coupling constants measured in solution are compared with those calculated from X-ray data. The conformations of the racemicmore » mixture and plus enantiomer of methadone hydrochloride have been shown to be very similar in the solid state, where minor differences in conformation can be seen by comparing NMR spectra obtained for the solids. Also shown is that the molecules of methadone hydrochloride have conformations in polar and in nonpolar solvents which are very similar to the conformation of the molecules in the solid state.« less

[The effectiveness of cevimeline hydrochloride on dry cough in Sjögren's syndrome].

PubMed

Nishinarita, Makoto; Hanzawa, Midori; Iikuni, Noriko; Ota, Syuji

2004-04-01

Dry cough in Sjögren syndrome (SS) is not an uncommon symptom observed in clinical fields. However, effective treatments for the cough have not been established. The recently introduced cevimeline hydrochloride, a muscarinic receptor stimulant, has been confirmed to be definitely effective for xerostomia of SS. In the present study, the effectiveness of cevimeline hydrochloride on dry cough was studied in 9 Sjögren patients and evaluated using the visual analog scale (VAS) and face scale. Improvement of dry cough was observed in 8 out of the 9 patients, suggesting the effectiveness of cevimeline hydrochloride. Although the detailed etiology of dry cough in SS is unknown, the result of the study suggested the mechanism that cevimeline hydrochloride increased the secretion in the airway mucus, improving dry bronchial conditions. Further studies are needed with more subjects.

Developmental rates of immatures of three Chrysomya species (Diptera: Calliphoridae) under the effect of methylphenidate hydrochloride, phenobarbital, and methylphenidate hydrochloride associated with phenobarbital.

PubMed

Rezende, Fábio; Alonso, Marcela A; Souza, Carina M; Thyssen, Patrícia J; Linhares, Arício X

2014-05-01

Entomotoxicology is focused on obtaining data on necrophagous entomofauna, for criminal investigations purposes. This study aimed to evaluate the effect of different concentrations of methylphenidate hydrochloride, phenobarbital, and their association on the developmental rate, larval and pupal survivorship, and the interval of emergence of adults of Chrysomya albiceps (Wiedemann), Chrysomya megacephala (Fabricius), and Chrysomya putoria (Wiedemann) (Diptera: Calliphoridae). Considering the therapeutic dose (TD) of methylphenidate hydrochloride (0.29 mg/Kg), the concentrations tested were 10× TD, 50× TD, and 100× TD. For phenobarbital, the concentrations used were 1× TD (=150 mg/Kg), 3.3× TD, and 6.7× TD. For the association of the drugs, the combinations used were 10× TD-methylphenidate hydrochloride plus 1× TD-phenobarbital, 50× TD-methylphenidate hydrochloride plus 3.3× TD-phenobarbital, and 100× TD-methylphenidate hydrochloride plus 6.7× TD-phenobarbital. The control group, without addition of drug, was maintained under the same conditions of temperature (25 ± 1 °C), humidity (70 ± 10%), and photoperiod (12 h). Specimens of each group were weighed every 12 h until pupariation. The developmental rate of the three Chrysomya species immatures was monitored. For C. albiceps the developmental time was delayed in 24 h for methylphenidate hydrochloride group and in 12 h for the phenobarbital and the drugs association groups. The effect was observed only at specific ages for C. megacephala, without altering the developmental time. For C. putoria, the developmental time was delayed in 12 h for methylphenidate hydrochloride group and in 24 h for the phenobarbital and the drugs association groups. The emergence interval was similar among all experimental groups, but larval and pupal viabilities were affected in different ways.

Influence of limonene on the bioavailability of nicardipine hydrochloride from membrane-moderated transdermal therapeutic systems in human volunteers.

PubMed

Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P

2002-10-24

The aim of the present study was to develop a membrane-moderated transdermal therapeutic system (TTS) of nicardipine hydrochloride using 2%w/w hydroxy propyl cellulose (HPC) gel as a reservoir system containing 4%w/w of limonene as a penetration enhancer. The permeability flux of nicardipine hydrochloride through ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate (VA) content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38 or TACKWHITE A 4MED) on the permeability of nicardipine hydrochloride through EVA membrane 2825 (28% w/w VA) or membrane/skin composite was also studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE 4A MED/skin composite was higher than that coated with MA-31or MA-38. Thus a new TTS for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE 4A MED and 2%w/w HPC gel as reservoir containing 4%w/w of limonene as a penetration enhancer. The bioavailability studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady state plasma concentration of the drug with minimal fluctuations for 20 h with improved bioavailability in comparison with the immediate release capsule dosage form. Copyright 2002 Elsevier Science B.V.

Influence of menthol and pressure-sensitive adhesives on the in vivo performance of membrane-moderated transdermal therapeutic system of nicardipine hydrochloride in human volunteers.

PubMed

Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P

2003-05-01

A membrane-moderated transdermal therapeutic system of nicardipine hydrochloride was developed using 2% w/w hydroxypropylcellulose (HPC) gel as a reservoir system containing 5% w/w of menthol as a penetration enhancer. The permeability flux of nicardipine hydrochloride through the ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38 or TACKWHITE A 4MED on the permeability of nicardipine hydrochloride through EVA 2825 membrane (28% w/w vinyl acetate) or EVA 2825 membrane/skin composite was also studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE A 4MED/skin composite was higher than that coated with MA-31 or MA-38. Thus, a new transdermal therapeutic system for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE A 4MED, and 2% w/w HPC gel as reservoir containing 5% w/w of menthol as a penetration enhancer. In vivo studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady-state plasma concentration of the drug with minimal fluctuations for 26h with improved bioavailability in comparison with the immediate release capsule dosage form.

Formulation and in vivo evaluation of membrane-moderated transdermal therapeutic systems of nicardipine hydrochloride using carvone as a penetration enhancer.

PubMed

Krishnaiah, Y S R; Satyanarayana, V; Bhaskar, P

2003-01-01

A membrane-moderated transdermal therapeutic system (TTS) of nicardipine hydrochloride was developed using 2%w/w hydroxy propyl cellulose (HPC) gel as a reservoir system containing 8%w/w of carvone as a penetration enhancer. The permeability flux of nicardipine hydrochloride through ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38, or TACKWHITE A 4MED) on the permeability of nicardipine hydrochloride through EVA 2825 membrane (28%w/w vinyl acetate) or EVA 2825 membrane/skin composite also was studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE A 4MED/skin composite was higher than that coated with MA-31 or MA-38. Thus, a new TTS for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE A 4MED and 2%w/w HPC gel as reservoir containing 8%w/w of carvone as a penetration enhancer. The bioavailability studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady-state plasma concentration of the drug with minimal fluctuations for 23 hr with improved bioavailability in comparison with the immediate-release capsule dosage form.

Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2005-12-01

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: 131I-chTNT; Abatacept, adalimumab, alemtuzumab, APC-8015, aprepitant, atazanavir sulfate, atomoxetine hydrochloride, azimilide hydrochloride; Bevacizumab, bortezomib, bosentan, buserelin; Caspofungin acetate, CC-4047, ChAGCD3, ciclesonide, clopidogrel, curcumin, Cypher; Dabigatran etexilate, dapoxetine hydrochloride, darbepoetin alfa, darusentan, denosumab, DMXB-Anabaseine, drospirenone, drospirenone/estradiol, duloxetine hydrochloride, dutasteride; Edodekin alfa, efaproxiral sodium, elaidic acid-cytarabine, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, eszopiclone, etonogestrel/testosterone decanoate, exenatide; Fulvestrant; Gefitinib, glycine, GVS-111; Homoharringtonine; ICC-1132, imatinib mesylate, iodine (I131) tositumomab, i.v. gamma-globulin; Levetiracetam, levocetirizine, lintuzumab, liposomal nystatin, lumiracoxib, lurtotecan; Manitimus, mapatumumab, melatonin, micafungin sodium, mycophenolic acid sodium salt; Oblimersen sodium, OGX-011, olmesartan medoxomil, omalizumab, omapatrilat, oral insulin; Parathyroid hormone (human recombinant), pasireotide, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, phVEGF-A165, pimecrolimus, pitavastatin calcium, plerixafor hydrochloride, posaconazole, pramlintide acetate, prasterone, pregabalin, PT-141; Quercetin; Ranolazine, rosuvastatin calcium, rubitecan, rupatadine fumarate; Sardomozide, sunitinib malate; Tadalafil, talactoferrin alfa, tegaserod maleate, telithromycin, testosterone transdermal patch, TH-9507, tigecycline, tiotropium bromide, tipifarnib, tocilizumab, treprostinil sodium; Valdecoxib, vandetanib, vardenafil hydrochloride hydrate, voriconazole. Copyright 2005 Prous Science. All rights reserved.

78 FR 27971 - Determination That REV-EYES (Dapiprazole Hydrochloride Ophthalmic Solution), 0.5%, Was Not...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-13

...] Determination That REV-EYES (Dapiprazole Hydrochloride Ophthalmic Solution), 0.5%, Was Not Withdrawn From Sale.... SUMMARY: The Food and Drug Administration (FDA) has determined that REV-EYES (dapiprazole hydrochloride... CFR 314.161)). FDA may not approve an ANDA that does not refer to a listed drug. REV-EYES (dapiprazole...

21 CFR 520.1242b - Levamisole hydrochloride tablet or oblet (bolus).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Levamisole hydrochloride tablet or oblet (bolus... § 520.1242b Levamisole hydrochloride tablet or oblet (bolus). (a) Chemical name. (-)-2,3,5,6-Tetrahydro... using in severely debilitated animals. (2) It is used in a tablet for sheep as follows: (i) Amount. 0...

New Drugs for Pretreatment of Organophosphonate Intoxication

DTIC Science & Technology

1990-02-20

amineHydrochlorides 40 1 -Phenylcyclohexane-l-carboxylic Acid 41 Dialkylaminoalkyl 1 -Phenylcycloalkane-l-carboxylate Hydrochlorides 41 3 -Formyl-4,5...cyclopropyl-CH2)- 3 -(Dimethylamino)propyl 1 -Phenylcyclopropane-l-carboxylate Hydrochloride (PRE-150). The recrystallized yield was 18.2 g (53...Arylcycloalkyl)methyl]amines 8 ct,a-Dialkylphenethylamines 9 Dialkylaminoalkyl 1 -Phenylcycloalkane-l-carboxylates 10 3 -Dialkylaminoalkyl-4,5

Brain targeted oral delivery of doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles against ketamine induced psychosis: behavioral, biochemical, neurochemical and histological alterations in mice.

PubMed

Yadav, Monu; Parle, Milind; Sharma, Nidhi; Dhingra, Sameer; Raina, Neha; Jindal, Deepak Kumar

2017-11-01

To develop statistically optimized brain targeted Tween 80 coated chitosan nanoparticulate formulation for oral delivery of doxycycline hydrochloride for the treatment of psychosis and to evaluate its protective effect on ketamine induced behavioral, biochemical, neurochemical and histological alterations in mice. 3 2 full factorial design was used to optimize the nanoparticulate formulation to minimize particle size and maximize entrapment efficiency, while independent variables chosen were concentration of chitosan and Tween 80. The optimized formulation was characterized by particle size, drug entrapment efficiency, Fourier transform infrared, Transmission electron microscopy analysis and drug release behavior. Pure doxycycline hydrochloride (25 and 50 mg/kg, p.o.) and optimized doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles (DCNP opt ) (equivalent to 25 mg/kg doxycycline hydrochloride, p.o.) were explored against ketamine induced psychosis in mice. The experimental studies for DCNP opt , with mean particle size 237 nm and entrapment efficiency 78.16%, elucidated that the formulation successfully passed through blood brain barrier and exhibited significant antipsychotic activity. The underlying mechanism of action was further confirmed by behavioral, biochemical, neurochemical estimations and histopathological study. Significantly enhanced GABA and GSH level and diminished MDA, TNF-α and dopamine levels were observed after administration of DCNP opt at just half the dose of pure doxycycline hydrochloride, showing better penetration of doxycyline hydrochloride in the form of Tween 80 coated nanoparticles through blood brain barrier. This study demonstrates the hydrophilic drug doxycycline hydrochloride, loaded in Tween 80 coated chitosan nanoparticles, can be effectively brain targeted through oral delivery and therefore represents a suitable approach for the treatment of psychotic symptoms.

Development and in vitro evaluation of carboxymethyl chitosan based drug delivery system for the controlled release of propranolol hydrochloride

NASA Astrophysics Data System (ADS)

Hernawan; Nur Hayati, Septi; Nisa, Khoirun; Wheni Indrianingsih, Anastasia; Darsih, Cici; Kismurtono, Muhammad

2017-12-01

Propranolol hydrochloride is a nonselective β-adrenergic drug and has been used as angina pectoris, antihypertensive, and that of many other cardiovascular disorders. It has a relatively short plasma half-life and duration of action are considered too short in certain circumstances. Thus, it’s fascinating to elongate the action. The tablet formula was based on extended-release by a propranolol hydrochloride based carboxymethyl chitosan matrix. Here we used direct compression technique with internal wet granulation to prepare the tablets. The tablets were evaluated for physical properties (hardness, weight variation test, friability) and in vitro release studies. There was no interaction observed between propranolol hydrochloride and excipients. Dissolution profiles of each formulation were followed zero order model. In conclusion, these results strongly suggest that in appropriate proportions carboxymethyl chitosan with internal granulation is suitable for formulating propranolol hydrochloride controlled release.

Evaluation of the potential carcinogenicity of 4-chloro-o-toluidine hydrochloride (3165-93-3). Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1988-06-01

4-Chloro-o-toluidine hydrochloride is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is Sufficient, and the evidence from human studies is No Data. The potency factor (F) for 4-chloro-o-toluidine hydrochloride is estimated to be 0.40 (mg/kg/day)(-1), placing it in potency group 3 according to the CAG's methodology for evaluating potential carcinogens. Combining the weight-of-evidence group and the potency group, 4-chloro-o-toluidine hydrochloride is assigned a LOW hazard ranking.

Effect of L-ornithine hydrochloride ingestion on intermittent maximal anaerobic cycle ergometer performance and fatigue recovery after exercise.

PubMed

Demura, Shinichi; Morishita, Koji; Yamada, Takayoshi; Yamaji, Shunsuke; Komatsu, Miho

2011-11-01

L-Ornithine plays an important role in ammonia metabolism via the urea cycle. This study aimed to examine the effect of L-ornithine hydrochloride ingestion on ammonia metabolism and performance after intermittent maximal anaerobic cycle ergometer exercise. Ten healthy young adults (age, 23.8 ± 3.9 year; height, 172.3 ± 5.5 cm; body mass, 67.7 ± 6.1 kg) with regular training experience ingested L-ornithine hydrochloride (0.1 g/kg, body mass) or placebo after 30 s of maximal cycling exercise. Five sets of the same maximal cycling exercise were conducted 60 min after ingestion, and maximal cycling exercise was conducted after a 15 min rest. The intensity of cycling exercise was based on each subject's body mass (0.74 N kg(-1)). Work volume (watt), peak rpm (rpm) before and after intermittent maximal ergometer exercise and the following serum parameters were measured before ingestion, immediately after exercise and 15 min after exercise: ornithine, ammonia, urea, lactic acid and glutamate. Peak rpm was significantly greater with L-ornithine hydrochloride ingestion than with placebo ingestion. Serum ornithine level was significantly greater with L-ornithine hydrochloride ingestion than with placebo ingestion immediately and 15 min after intermittent maximal cycle ergometer exercise. In conclusion, although maximal anaerobic performance may be improved by L-ornithine hydrochloride ingestion before intermittent maximal anaerobic cycle ergometer exercise, the above may not depend on increase of ammonia metabolism with L-ornithine hydrochloride.

Influence of stereoelectronic effects on the non-opioid analgesics gaboxadol and gaboxadol hydrochloride: Spectral and DFT study

NASA Astrophysics Data System (ADS)

Leenaraj, D. R.; Joe, I. Hubert

2018-05-01

The stereoelectronic properties of the molecular structure of most stable conformers of gaboxadol and gaboxadol hydrochloride have been studied using DFT/B3P86-LANL2DZ methodology. The energies of stable conformers of gaboxadol and gaboxadol hydrochloride are -494.2689 and -510.0117 hartrees, respectively. The stability of the molecules arising from stereoelectronic interactions, leading to its bioactivity, has been confirmed using natural bond orbital analysis. The natural bond orbital analysis of donor-acceptor (σ→σ* and n→σ*) interactions showed that the stereoelectronic hyperconjugative and anomeric interactions are exhibited in gaboxadol hydrochloride and gaboxadol, respectively. Lengthening of the axial and equatorial C-H bond lengths and natural population analysis support these results. Spectral features of gaboxadol hydrochloride have been explored by the Fourier transform infrared, Raman and Nuclear magnetic resonance spectroscopic techniques combined with density functional theory computations. NH+ … Cl- hydrogen bonding has been noticeable as a broad and strong absorption in the 2800-2400 cm-1 region. Broad peaks obtained by proton NMR are a result of the quadrupole effect of the N+ atom. Docking studies using representative GABA receptor crystal structures revealed that molecules containing azinane and isoxazole cores fit within the ligand binding domains, and the gaboxadol hydrochloride molecule shows the best binding energy with the 3D32 GABA receptor. Also, gaboxadol hydrochloride has obtained a high value of HOMO energy and a narrow HOMO- LUMO energy gap, which enhances reactivity.

40 CFR Appendix B to Subpart Nnn... - Free Formaldehyde Analysis of Insulation Resins by Hydroxylamine Hydrochloride

Code of Federal Regulations, 2013 CFR

2013-07-01

... buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3.4Magnetic stirrer and stir bars. 3.5250-mL beaker... N sodium hydroxide solution. 4.2Hydroxylamine hydrochloride solution, 100 grams per liter, pH... hydrochloric acid, and 0.1 N sodium hydroxide. 5.5Add 50 mL of the hydroxylamine hydrochloride solution...

40 CFR Appendix B to Subpart Nnn... - Free Formaldehyde Analysis of Insulation Resins by Hydroxylamine Hydrochloride

Code of Federal Regulations, 2014 CFR

2014-07-01

... buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3.4Magnetic stirrer and stir bars. 3.5250-mL beaker... N sodium hydroxide solution. 4.2Hydroxylamine hydrochloride solution, 100 grams per liter, pH... hydrochloric acid, and 0.1 N sodium hydroxide. 5.5Add 50 mL of the hydroxylamine hydrochloride solution...

Temperature-dependent THz vibrational spectra of clenbuterol hydrochloride

NASA Astrophysics Data System (ADS)

Yang, YuPing; Lei, XiangYun; Yue, Ai; Zhang, Zhenwei

2013-04-01

Using the high-resolution Terahertz Time-domain spectroscopy (THz-TDS) and the standard sample pellet technique, the far-infrared vibrational spectra of clenbuterol hydrochloride (CH), a β 2-adrenergic agonist for decreasing fat deposition and enhancing protein accretion, were measured in temperature range of 77-295 K. Between 0.2 and 3.6 THz (6.6-120.0 cm-1), seven highly resolved spectral features, strong line-narrowing and a frequency blue-shift were observed with cooling. However, ractopamine hydrochloride, with some structural and pharmacological similarities to clenbuterol hydrochloride, showed no spectral features, indicating high sensitivity and strong specificity of THz-TDS. These results could be used for the rapid and nondestructive CH residual detection in food safety control.

Molecular weight of Escherichia coli β-galactosidase in concentrated solutions of guanidine hydrochloride

PubMed Central

Erickson, Robert P.

1970-01-01

The molecular weight of Escherichia coli β-galactosidase was determined in 6m- and 8m-guanidine hydrochloride by meniscus-depletion sedimentation equilibrium, sedimentation velocity and viscosity. Sedimentation equilibrium revealed heterogeneity with the smallest component having a molecular weight of about 50000. At lower speeds, the apparent weight-average molecular weight is about 80000. By use of a calculation based on an empirical correlation for proteins that are random coils in 6m-guanidine hydrochloride, sedimentation velocity gave a molecular weight of 91000, and the intrinsic viscosity indicated a viscosity-average molecular weight of 84000. Heating in 6m-guanidine hydrochloride lowered the viscosity of β-galactosidase in a variable manner. PMID:4924171

Simultaneous HPTLC Determination of Rabeprazole and Itopride Hydrochloride From Their Combined Dosage Form.

PubMed

Suganthi, A; John, Sofiya; Ravi, T K

2008-01-01

A simple, precise, sensitive, rapid and reproducible HPTLC method for the simultaneous estimation of the rabeprazole and itopride hydrochloride in tablets was developed and validated. This method involves separation of the components by TLC on precoated silica gel G60F254 plate with solvent system of n-butanol, toluene and ammonia (8.5:0.5:1 v/v/v) and detection was carried out densitometrically using a UV detector at 288 nm in absorbance mode. This system was found to give compact spots for rabeprazole (Rf value of 0.23 0.02) and for itopride hydrochloride (Rf value of 0.75+/-0.02). Linearity was found to be in the range of 40-200 ng/spot and 300-1500 ng/spot for rabeprazole and itopride hydrochloride. The limit of detection and limit of quantification for rabeprazole were 10 and 20 ng/spot and for itopride hydrochloride were 50 and 100 ng/spot, respectively. The method was found to be beneficial for the routine analysis of combined dosage form.

The effect of tramadol hydrochloride on early life stages of fish.

PubMed

Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Berankova, Petra; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Vecerek, Vladimir; Svobodova, Zdenka

2016-06-01

The aim of this study was to perform the fish embryo acute toxicity test (FET) on zebrafish (Danio rerio) and the early-life stage toxicity test on common carp (Cyprinus carpio) with tramadol hydrochloride. The FET was performed using the method inspired by the OECD guideline 236. Newly fertilized zebrafish eggs were exposed to tramadol hydrochloride at concentrations of 10; 50; 100 and 200μg/l for a period of 144h. An embryo-larval toxicity test on C. carpio was performed according to OECD guideline 210 also with tramadol hydrochloride at concentrations 10; 50; 100 and 200μg/l for a period of 32 days. Hatching was significantly influenced in both acute and subchronic toxicity assays. Subchronic exposure also influenced early ontogeny, both morphometric and condition characteristics and caused changes in antioxidant enzyme activity. The LOEC value was found to be 10μg/l tramadol hydrochloride. Copyright © 2016 Elsevier B.V. All rights reserved.

IVABRADINE LOADED SOLID LIPID MICROPARTICLES: FORMULATION, CHARACTERIZATION AND OPTIMIZATION BY CENTRAL COMPOSITE ROTATABLE DESIGN.

PubMed

Hanif, Muhammad; Khan, Hafeez Ullah; Afzal, Samina; Sher, Muhammad

2017-01-01

The current research focused on improvement of oral bioavailability and decrease in dosing frequency of ivabradine (Iva) in order to enhance patient compliance by formulating novel sustained release Iva loaded solid lipid microparticles (SLMs) with the help of melt emulsification technique. SLMs formulations were designed with the help of three level central composite rotatable design (CCRD) to study the impact of independent variables like lipid concentration, surfactant concentration and stirring speed on responses - percentage yield (Y,) and entrapment efficiency (Y2). Compatibility between the drug and bees wax (BW) was checked by conducting Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). SLMs were further evaluated for rheological behavior, zeta potential, particle size and for morphology by scanning'electron microscope (SEM). The release of drug from SLMs was conducted by USP type-Il apparatus at pH 1.2, pH 6.8 and data were analyzed by different kinetic models like zero order, first order, Higuchi model, Korsmeyer-Peppas and Hixon-Crowell models. The rheo- logical studies approved the good flow behavior of SLMs and spherical smooth surface of SLMs was observed from SEM. DSC, FTIR and XRD studies concluded the lack of any possible interaction between formulation components. The size-of SLMs ranged from 300 to 500 pm and zeta potential study showed the presence of higher negative charge (-30 to -52 mV). Response Y, varied from 53 to 90% and response Y2 ranged from 29 to 78% indicating the effect of formulation variables. The obtained outcomes were analyzed by second order polynomial equation and suggested quadratic model was also validated. SLMs released Iva from 54 to 90% at pH 6.8 and was significantly (p 0.05) affected by BW concentration. The release mechanism followed the zero order and Korsmeyer-Peppas (n 0.85) kinetic models suggesting slow erosion along with diffusion mechanism for Iva release.

A Double-Blind, Placebo-Controlled Trial of Dexmethylphenidate Hydrochloride and D,l-Threo-Methylphenidate Hydrochloride in Children with Attention-Deficit-Hyperactivity Disorder

ERIC Educational Resources Information Center

Wigal, Sharon; Swanson, James M.; Feifel, David; Sangal, R. Bart; Elia, Josephine; Casat, Charles D.; Zeldis, Jerome B.; Conners, C. Keith

2004-01-01

Objective: To evaluate the efficacy and safety of dexmethylphenidate hydrochloride (d-MPH, Focalin[TM]) for the treatment of attention-deficit/hyperactivity disorder (ADHD) and to test an a priori hypothesis that d-MPH would have a longer duration of action than d,l-threo-methylphenidate (d,l-MPH). Method: This was a randomized, double-blind study…

Immobilisation of impala (Aepyceros melampus) with a ketamine hydrochloride/medetomidine hydrochloride combination, and reversal with atipamezole hydrochloride.

PubMed

Bush, M; Raath, J P; Phillips, L G; Lance, W

2004-03-01

A combination of medetomidine hydrochloride (medetomidine) and ketamine hydrochloride (ketamine) was evaluated in 16 boma-confined and 19 free-ranging impalas (Aepyceros melampus) to develop a non-opiate immobilisation protocol. In free-ranging impala a dose of 220 +/- 34 microg/kg medetomidine and 4.4 +/- 0.7 mg/kg ketamine combined with 7500 IU of hyaluronidase induced recumbency within 4.5 +/- 1.5 min, with good muscle relaxation, a stable heart rate and blood pH. PaCO2 was maintained within acceptable ranges. The animals were hypoxic with reduced oxygen saturation and low PaO2 in the presence of an elevated respiration rate, therefore methods for respiratory support are indicated. The depth of sedation was adequate for minor manipulations but additional anaesthesia is indicated for painful manipulations. Immobilisation was reversed by 467 +/- 108 microg/kg atipamezole hydrochloride (atipamezole) intramuscularly, but re-sedation was observed several hours later, possibly due to a low atipamezole:medetomidine ratio of 2:1. Therefore, this immobilisation and reversal protocol would subject impalas to possible predation or conspecific aggression following reversal if they were released into the wild. If the protocol is used on free-ranging impala, an atipamezole:medetomidine ratio of 5:1 should probably be used to prevent re-sedation.

Inhibitory effects of amines from Citrus reticulata on bleomycin-induced pulmonary fibrosis in rats

PubMed Central

ZHOU, XIAN-MEI; CAO, ZHEN-DONG; XIAO, NA; SHEN, QI; LI, JIAN-XIN

2016-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease for which, thus far, there are no effective treatments. The pericarp of Citrus reticulata, as a traditional herbal drug, has been used for the clinical treatment of lung-related diseases in China for many years. In the present study, the amines from the pericarp of Citrus reticulata were isolated, and their hydrochlorides were prepared. The results of screening using cultured human embryonic lung fibroblasts (hELFs) revealed that, of the amines, 4-methoxyphenethylamine hydrochloride (designated as amine hydrochloride 1) possessed the most potent inhibitory effect. Further in vivo experiments using a rat model of bleomycin-induced pulmonary fibrosis demonstrated that the oral administration of amine hydrochloride 1 significantly lowered the hydroxyproline content in both serum and lung tissue, and alleviated pulmonary alveolitis and fibrosis. Immunohistochemical analysis revealed that amine hydrochloride 1 exerted its inhibitory effect against IPF through the downregulation of lung transforming growth factor (TGF)-β1 protein expression. Our results demonstrated that amine hydrochloride 1 prevented the development of bleomycin-induced lung fibrosis in rats. Thus, our data suggest that the amines from the pericarp of Citrus reticulata have therapeutic potential for use in the treatment of IPF. PMID:26675886

Gateways to clinical trials.

PubMed

Bayes, M; Rabasseda, X; Prous, J R

2003-06-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AdGVVEGF121.10, anakinra, andolast, anidulafungin, APC-2059, l-arginine hydrochloride, aripiprazole, arzoxifene hydrochloride, asimadoline; Bexarotene, bimatoprost, bimosiamose, bizelesin, BMS-188667, botulinum toxin type B, bromfenac sodium, bryostatin 1; Cannabidiol, cariporide mesilate, CCI-1004, CDP-571, cerivastatin sodium, clevudine; Dalbavancin, darbepoetin alfa, decitabine, deligoparin sodium, diethylnorspermine, drotrecogin alfa (activated), DTaP-HBV-IPV/Hib-vaccine; E-5564, eculizumab, edodekin alfa, emtricitabine, enfuvirtide, (-)-epigallocatechin gallate, eplerenone, esomeprazole magnesium, etaquine, etoricoxib, ezetimibe; Fesoterodine, fipamezole hydrochloride, fondaparinux sodium, fosamprenavir calcium, frovatriptan, fulvestrant; Gadofosveset sodium, galiximab, ghrelin (human), glufosfamide; Homoharringtonine; Idraparinux sodium, imatinib mesylate, INS-37217; KRN-7000; L-651582, lafutidine, lanthanum carbonate, lenercept, levetiracetam, lusupultide; Magnesium sulfate, melatonin, mepolizumab, midostaurin, morphine hydrochloride, mozavaptan; Natalizumab, nesiritide; OPC-51803, oregovomab, oritavancin; Peginterferon alfa-2(a), pleconaril, plevitrexed, prasterone, pregabalin; Ranibizumab, Ro-31-7453, roxifiban acetate, rubitecan; SCV-07, SHL-749, sho-saiko-to, soblidotin, solifenacin succinate; Tegaserod maleate, telithromycin, tenecteplase, theraCIM, tipifarnib, travoprost; Valdecoxib, vardenafil hydrochloride hydrate, voriconazole; Ximelagatran; Ziprasidone hydrochloride, ZYC-00101. (c) 2003 Prous Science. All rights reserved.

Amino Acid and Vitamin Requirements of Several Bacteroides Strains

PubMed Central

Quinto, Grace

1966-01-01

Nutritional studies were performed on nine Bacteroides strains, by use of the methodology and media of anaerobic rumen microbiology. Ristella perfoetens CCI required l-arginine hydrochloride, l-tryptophan, l-leucine, l-histidine hydrochloride, l-cysteine hydrochloride, dl-valine, dl-tyrosine, and the vitamin calcium-d-pantothenate, since scant turbidity developed in media without these nutrients. R. perfoetens was stimulated by glycine, dl-lysine hydrochloride, dl-isoleucine, l-proline, l-glutamic acid, dl-alanine, dl-phenylalanine, dl-methionine, and the vitamins nicotinamide and p-aminobenzoic acid, since maximal turbidity developed more slowly in media without these nutrients than in complete medium. Medium A-23, which was devised for R. perfoetens, contained salts, 0.0002% nicotinamide and calcium d-pantothenate, 0.00001% p-aminobenzoic acid, 0.044% l-tryptophan, 0.09% l-glutamic acid, and 0.1% of the other 13 amino acids listed above. Zuberella clostridiformis and seven strains of R. pseudoinsolita did not require vitamins, and showed no absolute requirement for any one amino acid. Various strains produced maximal turbidity more slowly in media deficient in l-proline, glycine, l-glutamic acid, dl-serine, l-histidine hydrochloride, dl-alanine, or l-cysteine hydrochloride, than in complete medium. These eight strains grew optimally in medium A-23 plus 0.1% dl-serine but without vitamins. PMID:16349673

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride.

PubMed

Plöger, Gerlinde F; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, Dirk W; Langguth, Peter; Mehta, Mehul U; Parr, Alan; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Dressman, Jennifer B

2018-07-01

Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To elucidate the Biopharmaceutics Classification System (BCS) classification, experimental solubility and dissolution studies were also carried out. The antimalarial proguanil hydrochloride, effective via the parent compound proguanil and the metabolite cycloguanil, is not considered to be a narrow therapeutic index drug. Proguanil hydrochloride salt was shown to be highly soluble according to the U.S. Food and Drug Administration, World Health Organization, and European Medicines Agency guidelines, but data for permeability are inconclusive. Therefore, proguanil hydrochloride is conservatively classified as a BCS class 3 substance. In view of this information and the assessment of risks associated with a false positive decision, a BCS-based biowaiver approval procedure can be recommended for orally administered solid immediate release products containing proguanil hydrochloride, provided well-known excipients are used in usual amounts and provided the in vitro dissolution of the test and reference products is very rapid (85% or more are dissolved in 15 min at pH 1.2, 4.5, and 6.8) and is performed according to the current requirements for BCS-based biowaivers. Copyright © 2018 American Pharmacists Association®. All rights reserved.

Gateways to clinical trials.

PubMed

Tomillero, A; Moral, M A

2009-04-01

(+)-Dapoxetine hydrochloride, [(123)I]-BZA, 9-Aminocamptothecin; Abacavir sulfate/lamivudine, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Alvocidib hydrochloride, Ambrisentan, Amsilarotene, Anacetrapib, Anakinra, Apricitabine, Aripiprazole, Arsenic trioxide, Atazanavir sulfate, Atazanavir/ritonavir, Atrasentan, Azacitidine; Banoxantrone, Bazedoxifene acetate, Bevacizumab, Bexarotene, Biphasic insulin aspart, Bortezomib, Bosentan, Bromfenac; Cachectin, Calcipotriol/betamethasone dipropionate, Canakinumab, Carfilzomib, CAT-354, CCX-282, Certolizumab pegol, Cetuximab, Choline fenofibrate, Clevudine, Clofarabine, CNTO-328, Corifollitropin alfa, Crofelemer; Daptomycin, Darbepoetin alfa, Darunavir, Dasatinib, Decitabine, Deferasirox, Denosumab, Duloxetine hydrochloride, Dutasteride; Emtricitabine, Enfuvirtide, Entecavir, Epoetin zeta, Erlotinib hydrochloride, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Farglitazar, Febuxostat, Fosamprenavir calcium, FX-06; Gabapentin enacarbil, Gefitinib; HIVIS DNA; Imatinib mesylate, INCB- 18424, Indacaterol, Inotuzumab ozogamicin, Insulin detemir; JNJ-26854165; Lacosamide, Landiolol, Laromustine, Lenalidomide, Liposomal doxorubicin, L-NAME, Lopinavir, Lopinavir/ritonavir, Lumiracoxib; Maraviroc, Mepolizumab, Methoxy polyethylene glycol- epoetin-beta, Miglustat, MK-0493, MVA-CMDR, Mycophenolic acid sodium salt; Natalizumab, Nepafenac, Neratinib, Neridronic acid, Nesiritide, Nilotinib hydrochloride monohydrate; Olmesartan medoxomil, Omacetaxine mepesuccinate, Omalizumab; Paclitaxel poliglumex, Palifermin, Patupilone, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ ribavirin, Pemetrexed disodium, PHA-848125, Pitavastatin calcium, Posaconazole, Povidone-iodine liposome complex, Prasugrel, Pregabalin, Prucalopride; Raltegravir potassium, Retigabine, Revaprazan hydrochloride, rhFSH, Rilpivirine, Rivaroxaban, Romidepsin, Rosuvastatin calcium, RWJ-676070; SAR-109659, Sitagliptin phosphate monohydrate, Sorafenib, Stavudine/Lamivudine/Nevirapine, Sunitinib malate; Tadalafil, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tenofovir disoproxil fumarate/emtricitabine/efavirenz, Teriparatide, Tigecycline, Tiotropium bromide, Tipifarnib, Tipranavir, Tocilizumab, Trifluridine/TPI; UP-780; Vandetanib, Vardenafil hydrochloride hydrate, Vatalanib succinate, Vitespen, Vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan; Zoledronic acid monohydrate. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

[Intermediary effectiveness of procaine and procaine metabolites following oral administration].

PubMed

Kaemmerer, K; Kietzmann, M

1989-01-01

The influence of orally administrated procaine hydrochloride and of its metabolites diethylaminoethanol, monoethylaminoethanol and ethanolamine on specific intermediary processes in rats was tested. While the animals got procaine hydrochloride in a single dose or via food the incorporation rate of amino acids in protein was measured in homogenisates of liver tissue by the incorporation of a mixture of 14C-amino acids. Procaine hydrochloride, the commercial product K. H. 3, as well as diethylaminoethanol, monoethylaminoethanol and ethanolamine increased the amino acid incorporation rate in a dose and time dependent mode, while p-aminobenzoic acid remained without any effect. The dose of procaine hydrochloride inducing a maximal reaction was in the range of 50 to 100 mg/kg b. w. (250 to 500 mg/kg food). The minimal active dose was nearly at 10 mg/kg b. w. Paying regard to a metabolic factor of 10 the effective dose-range is nearly the dose used in experience with human beings to influence geriatric complaints. In the study described here haematoporphyrine (a component of the commercial product K. H. 3, not absorbed) shows no specific intermediary effect. May be it promotes the intestinal absorption of procaine hydrochloride by protection against intestinal hydrolysis. The intermediary effect of procaine hydrochloride is to measure on cellular or subcellular level without compatibility to the activity as a local anaesthetic. With regard to other intermediary effects mentioned in the literature like growth promotion or inhibition of monoamine oxidase activity, it is discussed whether the increase of the hepatic amino acid incorporation rate is corresponding to geriatric experiences made with procaine hydrochloride.

A validated high performance thin layer chromatography method for determination of yohimbine hydrochloride in pharmaceutical preparations

PubMed Central

Badr, Jihan M.

2013-01-01

Background: Yohimbine is an indole alkaloid used as a promising therapy for erectile dysfunction. A number of methods were reported for the analysis of yohimbine in the bark or in pharmaceutical preparations. Materials and Method: In the present work, a simple and sensitive high performance thin layer chromatographic method is developed for determination of yohimbine (occurring as yohimbine hydrochloride) in pharmaceutical preparations and validated according to International Conference of Harmonization (ICH) guidelines. The method employed thin layer chromatography aluminum sheets precoated with silica gel as the stationary phase and the mobile phase consisted of chloroform:methanol:ammonia (97:3:0.2), which gave compact bands of yohimbine hydrochloride. Results: Linear regression data for the calibration curves of standard yohimbine hydrochloride showed a good linear relationship over a concentration range of 80–1000 ng/spot with respect to the area and correlation coefficient (R2) was 0.9965. The method was evaluated regarding accuracy, precision, selectivity, and robustness. Limits of detection and quantitation were recorded as 5 and 40 ng/spot, respectively. The proposed method efficiently separated yohimbine hydrochloride from other components even in complex mixture containing powdered plants. The amount of yohimbine hydrochloride ranged from 2.3 to 5.2 mg/tablet or capsule in preparations containing the pure alkaloid, while it varied from zero (0) to 1.5–1.8 mg/capsule in dietary supplements containing powdered yohimbe bark. Conclusion: We concluded that this method employing high performance thin layer chromatography (HPTLC) in quantitative determination of yohimbine hydrochloride in pharmaceutical preparations is efficient, simple, accurate, and validated. PMID:23661986

A validated high performance thin layer chromatography method for determination of yohimbine hydrochloride in pharmaceutical preparations.

PubMed

Badr, Jihan M

2013-01-01

Yohimbine is an indole alkaloid used as a promising therapy for erectile dysfunction. A number of methods were reported for the analysis of yohimbine in the bark or in pharmaceutical preparations. In the present work, a simple and sensitive high performance thin layer chromatographic method is developed for determination of yohimbine (occurring as yohimbine hydrochloride) in pharmaceutical preparations and validated according to International Conference of Harmonization (ICH) guidelines. The method employed thin layer chromatography aluminum sheets precoated with silica gel as the stationary phase and the mobile phase consisted of chloroform:methanol:ammonia (97:3:0.2), which gave compact bands of yohimbine hydrochloride. Linear regression data for the calibration curves of standard yohimbine hydrochloride showed a good linear relationship over a concentration range of 80-1000 ng/spot with respect to the area and correlation coefficient (R(2)) was 0.9965. The method was evaluated regarding accuracy, precision, selectivity, and robustness. Limits of detection and quantitation were recorded as 5 and 40 ng/spot, respectively. The proposed method efficiently separated yohimbine hydrochloride from other components even in complex mixture containing powdered plants. The amount of yohimbine hydrochloride ranged from 2.3 to 5.2 mg/tablet or capsule in preparations containing the pure alkaloid, while it varied from zero (0) to 1.5-1.8 mg/capsule in dietary supplements containing powdered yohimbe bark. We concluded that this method employing high performance thin layer chromatography (HPTLC) in quantitative determination of yohimbine hydrochloride in pharmaceutical preparations is efficient, simple, accurate, and validated.

Compatibility of cholecalciferol, haloperidol, imipramine hydrochloride, levodopa/carbidopa, lorazepam, minocycline hydrochloride, tacrolimus monohydrate, terbinafine, tramadol hydrochloride and valsartan in SyrSpend SF PH4 oral suspensions.

PubMed

Polonini, H C; Silva, S L; Cunha, C N; Brandão, M A F; Ferreira, A O

2016-04-01

A challenge with compounding oral liquid formulations is the limited availability of data to support the physical, chemical and microbiological stability of the formulation. This poses a patient safety concern and a risk for medication errors. The objective of this study was to evaluate the compatibility of the following active pharmaceutical ingredients (APIs) in 10 oral suspensions, using SyrSpend SF PH4 (liquid) as the suspending vehicle: cholecalciferol 50,000 IU/mL, haloperidol 0.5 mg/mL, imipramine hydrochloride 5.0 mg/mL, levodopa/carbidopa 5.0/1.25 mg/mL, lorazepam 1.0 mg/mL, minocycline hydrochloride 10.0 mg/mL, tacrolimus monohydrate 1.0 mg/mL, terbinafine 25.0 mg/mL, tramadol hydrochloride 10.0 mg/mL and valsartan 4.0 mg/mL. The suspensions were stored both refrigerated (2 - 8 degrees C) and at controlled room temperature (20 - 25 degrees C). This is the first stability study for these APIs in SyrSpend SF PH4 (liquid). Further, the stability of haloperidol,ilmipramine hydrochloride, minocycline, and valsartan in oral suspension has not been previously reported in the literature. Compatibility was assessed by measuring percent recovery at varying time points throughout a 90 days period. Quantification of the APIs was performed by high performance liquid chromatography (HPLC-UV). Given the percentage of recovery of the APIs within the suspensions, the beyond-use date of the final preparations was found to be at least 90 days for most suspensions both refrigerated and at room temperature. Exceptions were: Minocycline hydrochloride at both storage temperatures (60 days), levodopa/carbidopa at room temperature (30 days), and lorazepam at room temperature (60 days). This suggests that compounded suspensions of APIs from different pharmacological classes in SyrSpend SF PH4 (liquid) are stable.

[Simultaneous determination of five cold medicine ingredients in paracetamol triprolidine hydrochloride and pseudoephedrine hydrochloride tablets by pH/organic solvent double-gradient high performance liquid chromatography].

PubMed

Xuan, Xueyi; Huang, Lina; Pan, Xiaoling; Li, Ning

2013-02-01

A pH/organic solvent double-gradient mode in reversed-phase high performance liquid chromatography (HPLC) has been established as a new approach to the simultaneous determination of acetaminophen, caffeine, salicylamide, pseudoephedrine hydrochloride and triprolidine hydrochloride in paracetamol triprolidine hydrochloride and pseudoephedrine hydrochloride tablets. Through the optimization of the organic solvent gradient mode and pH/organic solvent double-gradient mode, the optimum double-gradient HPLC system of the five cold medicine ingredients has been built. The determination was carried out on a Diamonsiol C18 column (250 mm x 4.6 mm, 5 microm). The mobile phase consisted of methanol, 0.05 mol/L ammonium acetate solution and 0.08 mol/L acetic acid solution. The column temperature was set at 30 degrees C. The flow rate was 1.0 mL/min. The sample was measured at multiple wavelengths: 0-6 min, 280 nm; 6-7 min, 257 nm; 7-14 min, 280 nm; 14 min, 233 nm. The separation of the five cold medicine ingredients in the tablets was achieved in 25.5 min. The linear ranges of acetaminophen, pseudoephedrine hydrochloride, caffeine, salicylamide and triprolidine hydrochloride were 0.055 -0.998 g/L, 0.053-0.946 g/L, 0.007-0.129 g/L, 0.035-0.622 g/L and 0.002-0.039 g/L, respectively, with their correlation coefficients greater than 0.999 0. The detection limits (S/N = 3) were 0.09, 6, 0.02, 0.128 and 0.02 mg/L, respectively. Their mean recoveries were 97.9%-102.8%. The advantage of the method is the simultaneous determination of acidic, neutral and basic compounds. It also can improve the column efficiency of the analyte, compress the half-peak width and reduce the trailing. The optimized and validated method can be used for the simultaneous determination of the five cold medicine ingredients in the tablets.

Pharmacokinetics of hydromorphone hydrochloride after intravenous and intramuscular administration of a single dose to American kestrels (Falco sparverius)

USGS Publications Warehouse

Guzman, David Sanchez-Migallon; KuKanich, Butch; Drazenovich, Tracy L.; Olsen, Glenn H.; Paul-Murphy, Joanne R.

2014-01-01

Results indicated hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with a short terminal half-life, rapid plasma clearance, and large volume of distribution in American kestrels. Further studies regarding the effects of other doses, other administration routes, constantrate infusions, and slow release formulations on the pharmacokinetics of hydromorphone hydrochloride and its metabolites in American kestrels may be indicated.

Benzydamine hydrochloride in prevention and management of pain in oral mucositis associated with radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Epstein, J.B.; Stevenson-Moore, P.

1986-08-01

Benzydamine hydrochloride rinse reduced pain associated with radiation mucositis when it was used during the course of radiation therapy. Fewer patients using benzydamine rinse required systemic analgesics. All patients using benzydamine tolerated the rinse well and continued with regular rinsing throughout the course of radiation therapy. Benzydamine hydrochloride is currently undergoing clinical trials in the United States for application for approval from the Food and Drug Administration.

Effects on fawn survival of multiple immobilizations of captive pregnant white-tailed deer

USGS Publications Warehouse

DelGiudice, G.D.; Mech, L.D.; Paul, W.J.; Karns, P.D.

1986-01-01

Fawn viability was tested in captive, pregnant white-tailed deer (Odocoileus virginianus) immobilized with xylazine hydrochloride and ketamine hydrochloride and reversed by yohimbine hydrochloride or tolazoline hydrochloride. Nine pregnant does were immobilized 10 times each from December 1984 to May 1985. Their mean parturition date was 8 June. The number of fawns produced per pregnant doe was 1.88. Mean weight of newborn fawns was 4.18 kg. Seventy-five percent of the does produced twins or triplets. Three (20%) fawns died postnatally within 48 hr, but the remaining 12 survived for the full 72 hr they were allowed to remain with their dams. These observations compare favorably with those of non-immobilized captive deer on similar diets.

In vitro sensitivities to antimicrobial drugs of ureaplasmas isolated from the bovine respiratory tract, genital tract and eye.

PubMed

Kishima, M; Hashimoto, K

1979-09-01

The sensitivity to 18 antimicrobial drugs was examined for 66 strains of Ureaplasma sp isolated from respiratory tracts of calves suffering from enzootic pneumonia, urinary tracts of bulls and eyes of cows suffering from infectious bovine kerato-conjunctivitis. Furamizole, tiamulin fumarate, erythromycin lactobionate, malidomycin C, doxycycline hydrochloride, kitasamycin tartrate, tylosin tartrate, T-2636C, tetracycline hydrochloride, oxytetracycline hydrochloride, chlortetracycline hydrochloride, oleandomycin phosphate, furazolidone, spiramycin adipate, chloramphenicol and thiophenicol showed strong inhibiting activity on all the test strains. Among them, furamizole, tiamulin fumarate and erythromycin lactobionate were most active. Kanamycin sulphate showed weak activity on all the strains tested. The differences in origin of the test strains did not affect their sensitivity to any of the drugs.

Fourth-order derivative spectrophotometric method for simultaneous determination of pseudoephedrine and naproxen in pharmaceutical dosage forms

PubMed Central

Souri, Effat; Mosafer, Amir; Tehrani, Maliheh Barazandeh

2016-01-01

Combination dosage forms of naproxen sodium and pseudoephedrine hydrochloride are used for symptomatic treatment of cold and sinus disorders. In this study, fourth-order derivative spectrophotometric method was used for simultaneous determination of naproxen sodium and pseudoephedrine hydrochloride. The method was linear over the range of 2-28 μg/ml for pseudoephedrine hydrochloride and 4-200 μg/ml for naproxen sodium. The within-day and between-day coefficient of variation values were less than 5.8% and 2.5% for pseudoephedrine hydrochloride and naproxen sodium, respectively. The application of the proposed method for simultaneous determination of naproxen and pseudoephedrine in dosage forms was demonstrated without any special pretreatment. PMID:27168748

[Neurotropic effect of B vitamins in the complex treatment of pain syndrome].

PubMed

Shavlovskaya, O A

Combined vitamin preparations in therapeutic doses are used, along with simple analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), muscle and epidural blockade, for the relief of acute pain. It is recommended to use the B vitamin preparation neuromultivit. The tablet form of this preparation contains vitamin thiamine hydrochloride (100 mg), pyridoxine hydrochloride (200 mg), cyanocobalamin (0.2 mg), and injectable form includes thiamine hydrochloride (100mg), pyridoxine hydrochloride (100 mg), cyanocobalamin (1 mg). The efficacy of neuromultivit in a two stage scheme (intramuscular injections of 2 ml daily for 5-10 days with further injections 2-3 times a week for 2-3 weeks at the initial stage and 1 tablet 3 times a day for 4 weeks at the second stage) was shown.

Therapeutic effectiveness of medications taken during spaceflight

NASA Technical Reports Server (NTRS)

Pool, Sam L.; Putcha, Lakshmi

1992-01-01

The therapeutic effectiveness of medications during spaceflight is considered in light of extensive anecdotal and experimental evidence. Attention is given to a range of medications for space motion sickness, sleeplessness, and physical discomfort. About 70 individual cases are reviewed in which crewmembers used such medications as: (1) scopolamine hydrobromide, dextroamphetamine sulfate, and promethazine hydrochloride for motion sickness; (2) metoclopramide hydrochloride and naloxone hydrochloride for bowel motility; and (3) aspirin and acetaminophen for headache and back pain. The effectiveness of orally ingested medications for space motion sickness is shown to be very low, while promethazine hydrochloride is effective when administered intramuscularly. The medications for pain are shown to be generally effective, and the use of sleep-inducing medications is limited by potentially detrimental performance effects.

[A prospective multicenter randomized controlled clinical study on the efficacy and safety of Guaifenesin compound pseudoephedrine hydrochloride oral solution].

PubMed

Lu, Quan

2010-03-01

To evaluate efficacy and safety of Guaifenesin compound pseudoephedrine hydrochloride oral solution for the treatment of cough, expectoration, nasal congestion and runny nose in children. This was a prospective multicenter randomized single-blind, parallel-controlled clinical study. A total of 10 centers participated in this study, the actual number of cases in line with the program was 412, of whom 205 cases in trial group were treated with Guaifenesin compound pseudoephedrine hydrochloride oral solution, and 207 cases in control group with ambroxol hydrochloride oral solution, treatment of both groups persisted for 7 days. The improvement rate of each single symptom and the combined symptoms and the overall effective rate were compared between the two groups. The adverse drug reactions and compliance were assessed as well. The treatment of both groups showed efficacy. Except sputum stickiness, the improvement of all symptoms in trial group was superior to that in the control group on the 3rd day after treatment (P < 0.05) and except nasal congestion, the efficacy in all the other symptoms of trial group was better than that in the control group as well on the 7th day (P < 0.01). The improvement rate for combined symptoms of Guaifenesin compound pseudoephedrine hydrochloride oral solution was 82.9% and the overall efficacy rate was 89.3%. Guaifenesin compound Pseudoephedrine hydrochloride oral solution had higher compliance and its adverse event rate was merely 0.92%. Guaifenesin compound pseudoephedrine hydrochloride oral solution showed significant efficacy and safety in children for treatment of cough, expectoration, nasal congestion and runny nose caused by common cold or acute tracheobronchitis.

UPLC and LC-MS studies on degradation behavior of irinotecan hydrochloride and development of a validated stability-indicating ultra-performance liquid chromatographic method for determination of irinotecan hydrochloride and its impurities in pharmaceutical dosage forms.

PubMed

Kumar, Navneet; Sangeetha, Dhanaraj; Reddy, Sunil P

2012-10-01

The objective of the current investigation was to study the degradation behavior of irinotecan hydrochloride under different International Conference on Harmonization (ICH) recommended stress conditions using ultra-performance liquid chromatography and liquid chromatography-mass spectrometry and to establish a validated stability-indicating reverse-phase ultra-performance liquid chromatographic method for the quantitative determination of irinotecan hydrochloride and its seven impurities and degradation products in pharmaceutical dosage forms. Irinotecan hydrochloride was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Irinotecan hydrochloride was found to degrade significantly in oxidative and base hydrolysis and photolytic degradation conditions. The degradation products were well resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. Chromatographic separation was achieved on a Waters Acquity BEH C8 (100 × 2.1 mm) 1.7-µm column with a mobile phase containing a gradient mixture of solvent A (0.02M KH(2)PO(4) buffer, pH 3.4) and solvent B (a mixture of acetonitrile and methanol in the ratio of 62:38 v/v). The mobile phase was delivered at a flow rate of 0.3 mL/min with ultraviolet detection at 220 nm. The run time was 8 min, within which irinotecan and its seven impurities and degradation products were satisfactorily separated. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. This method was also suitable for the assay determination of irinotecan hydrochloride in pharmaceutical dosage forms.

Subconjunctival delivery of antibiotics in a controlled-release system: a novel anti-infective prophylaxis approach for cataract surgery.

PubMed

Cardillo, José A; Paganelli, Fernando; Melo, Luiz A S; Silva, Arnobio A; Pizzolitto, Antonio C; Oliveira, Anselmo G

2010-01-01

To compare the efficacy of subconjunctival injection of a combination of triamcinolone and ciprofloxacin hydrochloride, 2 mg/0.1 mL, in a controlled-release system (DuoCat) with that of ciprofloxacin hydrochloride, 0.3%, eyedrops for infection prophylaxis. Rabbit eyes were injected subconjunctivally with a combination of triamcinolone and ciprofloxacin hydrochloride, 2 mg/0.1 mL, or ciprofloxacin hydrochloride, 2 mg/0.1 mL, alone. The aqueous and vitreous humor pharmacokinetic profiles were compared with those of a single drop of ciprofloxacin hydrochloride, 0.3%, 6 times daily. In 45 rabbits, Staphylococcus aureus was injected into the anterior chamber: 15 randomly received 1 drop of ciprofloxacin hydrochloride, 0.3%, every 4 hours during 24 hours; 15 received drops of balanced salt solution; and 15 received a combination of triamcinolone and ciprofloxacin hydrochloride, 2 mg/0.1 mL. After 24 hours, endophthalmitis scores were recorded, aqueous and vitreous humors underwent culture, and histologic analysis was performed. The combined triamcinolone and ciprofloxacin treatment allowed higher intraocular levels of ciprofloxacin. The median endophthalmitis clinical scores for the combination of triamcinolone and ciprofloxacin and ciprofloxacin-only eyedrop groups were equivalent (P = .42) and were significantly lower than those of the balanced salt solution group (P < .001). The culture was negative for S aureus in the combined triamcinolone and ciprofloxacin and ciprofloxacin eyedrop regimens. No adverse effects were observed with either route. Ciprofloxacin eyedrops and combined triamcinolone and ciprofloxacin were equally tolerated and efficacious. The combined triamcinolone and ciprofloxacin treatment may eliminate noncompliance issues and may prove to be a valuable clinical tool for surgical prophylaxis. The combined triamcinolone and ciprofloxacin treatment may be a new useful strategy for surgical prophylaxis.

Spectrophotometric simultaneous determination of Rabeprazole Sodium and Itopride Hydrochloride in capsule dosage form

NASA Astrophysics Data System (ADS)

Sabnis, Shweta S.; Dhavale, Nilesh D.; Jadhav, Vijay. Y.; Gandhi, Santosh V.

2008-03-01

A new simple, economical, rapid, precise and accurate method for simultaneous determination of rabeprazole sodium and itopride hydrochloride in capsule dosage form has been developed. The method is based on ratio spectra derivative spectrophotometry. The amplitudes in the first derivative of the corresponding ratio spectra at 231 nm (minima) and 260 nm were selected to determine rabeprazole sodium and itopride hydrochloride, respectively. The method was validated with respect to linearity, precision and accuracy.

Spectrophotometric simultaneous determination of rabeprazole sodium and itopride hydrochloride in capsule dosage form.

PubMed

Sabnis, Shweta S; Dhavale, Nilesh D; Jadhav, Vijay Y; Gandhi, Santosh V

2008-03-01

A new simple, economical, rapid, precise and accurate method for simultaneous determination of rabeprazole sodium and itopride hydrochloride in capsule dosage form has been developed. The method is based on ratio spectra derivative spectrophotometry. The amplitudes in the first derivative of the corresponding ratio spectra at 231nm (minima) and 260nm were selected to determine rabeprazole sodium and itopride hydrochloride, respectively. The method was validated with respect to linearity, precision and accuracy.

Pharmacokinetics of hydromorphone hydrochloride after intravenous and intramuscular administration of a single dose to American kestrels (Falco sparverius)

USGS Publications Warehouse

Sanchez-Migallon Guzman, David; KuKanich, Butch; Drazenovich, Tracy L.; Olsen, Glenn H.; Paul-Murphy, Joanne R.

2014-01-01

Conclusion and Clinical Relevance—Results indicated hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with a short terminal half-life, rapid plasma clearance, and large volume of distribution in American kestrels. Further studies regarding the effects of other doses, other administration routes, constantrate infusions, and slow release formulations on the pharmacokinetics of hydromorphone hydrochloride and its metabolites in American kestrels may be indicated.

Effects of topical anesthetics on Pullalaria pullulans and Debaryomyces hansenii.

PubMed

Merdinger, E; Guthmann, W S; Mangine, F W

1969-09-01

The inhibitory effects of three topical anesthetics of various concentrations on the growth of Pullularia pullulans, Debaryomyces hansenii, and on pigment production by P. pullulans were investigated. The topical anesthetics were benoxinate hydrochloride, proparacaine hydrochloride, and tetracaine hydrochloride. In decreasing order, the inhibiting effects of the drugs on growth were benoxinate, tetracaine, and proparacaine for P. pullulans, and tetracaine, benoxinate, and proparacaine for D. hansenii. The pigment formation in P. pullulans was inhibited by the three drugs.

An evaluation of the histological effects of intra-articular methadone in the canine model.

PubMed

Jones, Timothy A; Hand, Walter R; Ports, Michael D; Unger, Daniel V; Herbert, Daniel; Pellegrini, Joseph E

2003-02-01

Methadone hydrochloride is an opiate that has pharmacodynamic and pharmacokinetic properties that suggest it may provide longer analgesia than morphine when administered via the intra-articular route. However, no studies to date have been conducted examining the effects of intra-articular methadone hydrochloride on local tissues. Therefore, the purpose of this study was to determine the histopathologic effects of intra-articular methadone hydrochloride on local tissues in the canine knee. Nine canines, 1 to 4 years old, weighing between 20 kg and 23 kg were used. All canines had their knees randomized to receive either bupivacaine, 0.5% with epinephrine 1:200,000 (4.5 mL), and 5 mg methadone hydrochloride (0.5 mL) for the study knee, or bupivacaine, 0.5% with epinephrine 1:200,000 (4.5 mL), and 0.5 mL normal saline for the control knee. Serum methadone hydrochloride levels were obtained on all canines at 6 and 24 hours. Canines were randomly assigned to 1 of 3 groups to be euthanized at either 24 hours, 14 days, or 28 days. Following euthanization and necropsy, synovial fluid levels and tissue samples were obtained and examined for histopathologic changes. Synovial fluid samples noted a few white blood cells at 24 hours and none at 14 and 28 days. Tissue samples showed no histopathologic changes, and serum concentration levels of methadone hydrochloride were negligible.

The efficacy of cetirizine hydrochloride on the pruritus of cats with atopic dermatitis: a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Wildermuth, Kerstin; Zabel, Sonja; Rosychuk, Rod A W

2013-12-01

Various antihistamines have been used in the management of feline atopic dermatitis, with variable reported benefit. To date, there have been no randomized, double-blind, placebo-controlled, crossover clinical trials on the use of this drug class in cats. To evaluate the clinical efficacy of cetirizine hydrochloride for the control of pruritus and dermatitis in cats diagnosed with atopic dermatitis. In this randomized, double-blind, placebo-controlled crossover clinical trial, 21 client-owned cats diagnosed with mild to moderate nonseasonal atopic dermatitis were randomly assigned to two groups. Cats in each group received either 1 mg/kg cetirizine hydrochloride or placebo once daily per os for 28 days followed by a 14 day wash-out period. Treatments were then crossed over, and cats received placebo or cetirizine hydrochloride for another 28 days. Owners marked a pruritus severity scale before inclusion in the study and weekly throughout the entire study period. Lesions were scored by the clinician using a Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03 modified for the cat before enrolment and at day 28 of each treatment. Nineteen cats completed the study. There were no statistically significant differences between treatment with cetirizine hydrochloride and placebo for modified CADESI-03 or pruritus scores. This study suggests that cetirizine hydrochloride cannot be recommended for the management of feline atopic dermatitis. © 2013 ESVD and ACVD.

[Effect of phenformin hydrochloride on pharmacokinetics of puerarin in rats].

PubMed

Deng, Ying; Li, Ning; Cui, Mei; Xiong, Zhi-li; Li, Fa-mei

2012-10-01

To study the effect of phenformin hydrochloride that may be illegally added in traditional Chinese medicine preparations on the pharmacokinetics of puerarin in rats. Rats were randomly divided into the single pueraria group and the phenformin hydrochloride combined with pueraria group. After oral administration in the two groups, their bloods were sampled at different time points to determine the drug concentration of puerarin in rat blood and calculate pharmacokinetic parameters. After oral administration with pueraria extracts and phenformin hydrochloride combined with pueraria extracts, the two groups showed main pharmacokinetic parameters as follows: Cmax were (2.39 +/- 1.01), (1.03 +/- 0.35) mg x L(-1), respectively; Tmax were (0.50 +/- 0.09), (1.5 +/- 0.5) h, respectively; Ke were (0.153 +/- 0.028), (0.172 +/- 0.042) h(-1), respectively; t(1/2) were (4.65 +/- 0.86), (4.20 +/- 0.81) h, respectively; AUC(0-t), were (5.73 +/- 2.60), (5.45 +/- 1.81) mg x h x L(-1), respectively; AUC(0-infinity) were (6.72 +/- 2.89), (6.26 +/- 1.88) mg x h x L(-1), respectively. Compared with the single puerarin group, the Cmax was significantly decreased (P < 0.05) and the Tmax was markedly longer (P < 0.01) than the hydrochloride combined with pueraria group. Phenformin hydrochloride can slow down the absorption process of puerarin and change the pharmacokinetic process of puerarin to some extent.

Chemical Immobilization of Sloth Bears (Melursus ursinus) with Ketamine Hydrochloride and Xylazine Hydrochloride: Hematology and Serum Biochemical Values

PubMed Central

Veeraselvam, M.; Sridhar, R.; Perumal, P.; Jayathangaraj, M. G.

2014-01-01

The present study was conducted to define the physiological responses of captive sloth bears immobilized with ketamine hydrochloride and xylazine hydrochloride and to determine and compare the values of hematology and serum biochemical parameters between sexes. A total of 15 sloth bears were immobilized using combination of ketamine hydrochloride and xylazine hydrochloride drugs at the dose rate of 5.0 milligram (mg) per kg body weight and 2.0 mg per kg body weight, respectively. The use of combination of these drugs was found satisfactory for the chemical immobilization of captive sloth bears. There were no significant differences observed in induction time and recovery time and physiological parameters such as heart rate, respiratory rate, and rectal temperature between sexes. Health related parameters comprising hematological values like packed cell volume (PCV), hemoglobin (Hb), red blood cell count (RBC), erythrocyte indices, and so forth and biochemical values like total protein, blood urea nitrogen (BUN), creatinine, alkaline amino-transferase (ALT), aspartate amino-transferase (AST), and so forth were estimated in 11 (5 males and 6 females) apparently healthy bears. Comparison between sexes revealed significant difference in PCV (P < 0.05) and mean corpuscular hemoglobin concentration (MCHC) (P < 0.05). The study might help to evaluate health profiles of sloth bears for appropriate line treatment. PMID:24876990

Netupitant and Palonosetron Hydrochloride

Cancer.gov

This page contains brief information about netupitant and palonosetron hydrochloride and a collection of links to more information about the use of this combination drug, research results, and ongoing clinical trials.

Trifluridine and Tipiracil Hydrochloride

Cancer.gov

This page contains brief information about trifluridine and tipiracil hydrochloride and a collection of links to more information about the use of this combination drug, research results, and ongoing clinical trials.

An evaluation of the influence of medetomidine hydrochloride and atipamezole hydrochloride on the arrhythmogenic dose of epinephrine in dogs during halothane anesthesia.

PubMed Central

Pettifer, G R; Dyson, D H; McDonell, W N

1996-01-01

Alterations in the arrhythmogenic dose of epinephrine (ADE) were determined following administration of medetomidine hydrochloride (750 micrograms/M2) and a saline placebo, or medetomidine hydrochloride (750 micrograms/M2), followed by specific medetomidine reversal agent, atipamezole hydrochloride (50 micrograms/kg) 20 min later, in halothane-anesthetized dogs (n = 6). ADE determinations were made prior to the administration of either treatment, 20 min and 4 h following medetomidine/saline or medetomidine/atipamezole administration. Epinephrine was infused for 3 min at increasing dose rates (2.5 and 5.0 micrograms/kg/min) until the arrhythmia criterion (4 or more intermittent or continuous premature ventricular contractions) was reached. The interinfusion interval was 20 min. There were no significant differences in the amount of epinephrine required to reach the arrhythmia criterion following the administration of either treatment. In addition, the ADE at each determination was not different between treatment groups. In this study, the administration of medetomidine to halothane-anesthetized dogs did not alter their arrhythmogenic response to infused epinephrine. PMID:8825986

Simultaneous HPTLC Determination of Rabeprazole and Itopride Hydrochloride From Their Combined Dosage Form

PubMed Central

Suganthi, A.; John, Sofiya; Ravi, T. K.

2008-01-01

A simple, precise, sensitive, rapid and reproducible HPTLC method for the simultaneous estimation of the rabeprazole and itopride hydrochloride in tablets was developed and validated. This method involves separation of the components by TLC on precoated silica gel G60F254 plate with solvent system of n-butanol, toluene and ammonia (8.5:0.5:1 v/v/v) and detection was carried out densitometrically using a UV detector at 288 nm in absorbance mode. This system was found to give compact spots for rabeprazole (Rf value of 0.23 0.02) and for itopride hydrochloride (Rf value of 0.75±0.02). Linearity was found to be in the range of 40-200 ng/spot and 300-1500 ng/spot for rabeprazole and itopride hydrochloride. The limit of detection and limit of quantification for rabeprazole were 10 and 20 ng/spot and for itopride hydrochloride were 50 and 100 ng/spot, respectively. The method was found to be beneficial for the routine analysis of combined dosage form. PMID:20046748

The radiolysis and radioracemization of amino acids on clays

NASA Technical Reports Server (NTRS)

Bonner, W. A.; Hall, H.; Chow, G.; Yi, L.; Lemmon, R. M.

1985-01-01

The effects of the surfaces of kaolinite and bentonite clays on the radiolysis and radioracemization of L-leucine and its hydrochloride salt have been investigated experimentally. L-leucine and its hydrochloride salt were deposited on the clays and the amino acid/clay preparations were irradiated by a Co-60 gamma-ray source which induced 2-89 percent radiolysis. The efficiency of radiolysis and radioracemization were measured using gas chromatography. Results were obtained for leucine in 0.1 M aqueous solution for comparison with the clay-deposted leucine and leucine hydrochloride. It is found that radiolysis and radioracemization in the samples occurred according to a pseudo-first-order rate law. Comparison of the specific rate constants showed that leucine and its hydrochloride salt were the most resistant to both radiolysis and radioracemization, followed by leucine and its hydrochloride salt on kaolin. Leucine and its HCl salt on bentonite, and leucine in aqueous solution were found to be the least resistant to radiolysis and radioracemization. The experimental results are intepreted with respect to the Vester-Ulbricht mechanism for the origin of optical activity.

Toxicology and carcinogenesis studies of methylphenidate hydrochloride (Cas No. 298-59-9) in F344/N rats and B6C3F1 mice (feed studies). Technical report series

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-07-01

Toxicology and carcinogenicity studies were conducted by administration of methylphenidate hydrochloride in feed to groups of 70 F344/N rats of each sex at doses of 0, 100, 500, or 1,0000 ppm and to groups of 70 B6C3F1 mice of each sex at doses of 0, 50, 250, or 500 ppm. Under the conditions of these 2-year feed studies, there was no evidence of carcinogenic activity of methylphenidate hydrochloride in male or female F344/N rats receiving 100, 500, or 1,000 ppm. There was some evidence of carcinogenic activity in male and female B6C3F1 mice, based on the occurrence of hepatocellular neoplasms.more » Treatment of female rats with methylphenidate hydrochloride was associated with a decrease in the incidence of mammary gland fibroadenomas. Administration of methylphenidate hydrochloride to male and female mice resulted in increased incidence of eosinophilic foci in the liver.« less

Daunorubicin Hydrochloride and Cytarabine Liposome

Cancer.gov

This page contains brief information about daunorubicin hydrochloride and cytarabine liposome and a collection of links to more information about the use of this drug, research results, and ongoing clinical trials.

21 CFR 520.2345e - Tetracycline oral liquid.

Code of Federal Regulations, 2011 CFR

2011-04-01

... sensitive to tetracycline hydrochloride, such as bacterial gastroenteritis due to Escherichia coli and... susceptible to tetracycline hydrochloride, such as bacterial gastroenteritis due to E. coli and urinary tract...

21 CFR 520.2345e - Tetracycline oral liquid.

Code of Federal Regulations, 2010 CFR

2010-04-01

... sensitive to tetracycline hydrochloride, such as bacterial gastroenteritis due to Escherichia coli and... susceptible to tetracycline hydrochloride, such as bacterial gastroenteritis due to E. coli and urinary tract...

Metabolism of amosulalol hydrochloride in man: quantitative comparison with laboratory animals.

PubMed

Kamimura, H; Sasaki, H; Kawamura, S

1985-05-01

The metabolism of amosulalol hydrochloride, (+/-)-5-[1-hydroxy-2-[[2-(o-methoxyphenoxy)ethyl]amino]ethyl]-2- methylbenzenesulphonamide hydrochloride, was studied in man and laboratory animals. Humans excreted 30.1% of dose as unchanged drug, and the sulphate conjugate of a 5-hydroxy metabolite, (+/-)-5-[1-hydroxy-2-[[2-(5-hydroxy-2-methoxyphenoxy)ethyl]-amino] ethyl]-2-methylbenzenesulphonamide, was the major metabolite. Amosulalol hydrochloride was extensively metabolized in animals with 10% or less excreted as unchanged drug. Hydroxylation of the 2-methyl group and O-demethylation of the o-methoxyphenoxy group were preferred in rats, and oxidative C-N cleavage yielding o-methoxyphenoxyacetic acid (M-5) preceded other reactions in dogs. Monkeys excreted almost equal amounts of the 5-hydroxy and 4-hydroxy metabolites as well as M-5.

Photoacoustic imaging to detect rat brain activation after cocaine hydrochloride injection

NASA Astrophysics Data System (ADS)

Jo, Janggun; Yang, Xinmai

2011-03-01

Photoacoustic imaging (PAI) was employed to detect small animal brain activation after the administration of cocaine hydrochloride. Sprague Dawley rats were injected with different concentrations (2.5, 3.0, and 5.0 mg per kg body) of cocaine hydrochloride in saline solution through tail veins. The brain functional response to the injection was monitored by photoacoustic tomography (PAT) system with horizontal scanning of cerebral cortex of rat brain. Photoacoustic microscopy (PAM) was also used for coronal view images. The modified PAT system used multiple ultrasonic detectors to reduce the scanning time and maintain a good signal-to-noise ratio (SNR). The measured photoacoustic signal changes confirmed that cocaine hydrochloride injection excited high blood volume in brain. This result shows PAI can be used to monitor drug abuse-induced brain activation.

[The use of natural and synthetic hydrophilic polymers in the formulation of metformin hydrochloride tablets with different profile release].

PubMed

Kołodziejczyk, Michał Krzysztof; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

2012-01-01

Metformin hydrochloride after buformin and phenformin belongs to the group of biguanid derivatives used as oral anti-diabetic drugs. The object of the study is the technological analysis and the potential effect of biodegradable macromolecular polymers on the technological and therapeutic parameters of oral anti-diabetic medicinal products with metformin hydrochloride: Siofor, Formetic, Glucophage, Metformax in doses of 500mg and 1000mg and Glucophage XR in a dose of 500 mg of modified release. Market therapeutic products containing 500 and 1000 mg of metformin hydrochloride in a normal formulation and 500 mg of metformin hydrochloride in a formulation of modified release were analyzed. Following research methods were used: technological analysis of tablets, study of disintegration time of tablets, evaluation of pharmaceutical availability of metformin hydrochloride from tested therapeutic products, mathematical and kinetic analysis of release profiles of metformin hydrochloride, statistical analysis of mean differences of release coefficients. The percentage of excipients in the XR formulation is higher and constitutes 50.5% of a tablet mass. However, in standard formulations the percentage is lower, between 5.5% and 12.76%. On the basis of the results of disintegration time studies, the analysed therapeutic products can be divided into two groups, regardless the dose. The first one are preparations with faster (not fast!) disintegration: Glucophage i Metformax. The second group are preparations with slower disintegration, more balanced in the aspect of a high dose of the biologically active substance: Formetic and Siofor. Products with a lower content of excipients (Metformax, Glucophage) disintegrate in a faster way. The disintegration rate of the products with a higher content of excipients (Formetic, Siofor) is slower. The appearance of metformin hydrochloride concentration in the gastrointestinal contents, balanced in time, caused by a slower disintegration-dissolving of a tablet, is conducive to the reduction of gastrointestinal side effects and better tolerance of the therapeutic product by a patient. The study on pharmaceutical availability indicated relevant kinetic differences between tested therapeutic products. They are particularly visible between standard formulations and the one with prolonged release (Glucophage XR500). Its release profile bears features of kinetics similar to zero-order reactions. Tested therapeutic products contain a large amount of the biologically active substance in relation to the content of excipients. A higher content of excipients in a single tablet mass distinguishes Siofor in comparison with Glucophage i Metformax. The excipients used in the formulations of tested preparations are comparable. A higher percentage of binding agents (HPMC, PVP) is observed, but there is a lack of typical disintegrants which results in a longer disintegration time up to 15 minutes. Siofor disintegrates at the same time as Formetic, but longer than Glucophage i Metformax. Considering the large content of the active substance and pharmacological properties of metformin hydrochloride, such a disintegration might have beneficial consequences, because the amount of the free active substance in the gastrointestinal tract will increase over the longer time period what will reduce the level of gastrointestinal side effects. The release profiles of metformin hydrochloride from tested therapeutic products are comparable. The Glucophage XR 500 formulation with the release kinetics of metformin hydrochloride similar to the zero-order kinetics is completely different from the others. The above is confirmed by the mathematical analysis of release profiles of metformin hydrochloride from tested preparations where equations of lines describing the release profile are characterized by similar values of correlation coefficients.

21 CFR 520.2345a - Tetracycline hydrochloride capsules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... organisms sensitive to tetracycline hydrochloride, such as bacterial gastroenteritis due to E. coli and urinary tract infections due to Staphylococcus spp. and E. coli. (3) Limitations. Federal law restricts...

21 CFR 520.2345a - Tetracycline hydrochloride capsules.

Code of Federal Regulations, 2011 CFR

2011-04-01

... organisms sensitive to tetracycline hydrochloride, such as bacterial gastroenteritis due to E. coli and urinary tract infections due to Staphylococcus spp. and E. coli. (3) Limitations. Federal law restricts...

[Study of selegiline and related compounds with x-ray diffraction].

PubMed

Simon, K; Böcskei, Z; Török, Z

1992-09-01

Selegiline and its parent compounds were studied by X-ray diffraction. It was established that the racemates of primary and secondary amines (p-fluoro-amphetamine, methamphetamine, p-fluoro-methamphetamine) hydrochloride do not form racemic compounds but crystalline as conglomerates, at the same time tertiary amines like selegiline and p-fluoro-selegiline hydrochlorides do. The crystalline structure of five enantiomeric hydrochlorides were determined, the CPhe-C-C-N torsion angle is anti-periplanar in all cases but in p-fluoro-amphetamine where it is gauche.

Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

NASA Astrophysics Data System (ADS)

Bhunia, Tridib; Goswami, Luna; Chattopadhyay, Dipankar; Bandyopadhyay, Abhijit

2011-08-01

Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

Characterization of the Polypeptides in Varicella Zoster Virus - Infected Cells

DTIC Science & Technology

1984-03-16

DNA binding proteins.. 127 38. Autoradiogram of guanidine hydrochloride wash of DNA cellulose columns 129 Figure Page 32 39. Autoradiogram of P...of purification was seventy-fold 35 1^ with respect to host proteins and the S-methionine or G- glucosamine labeled virions were subjected to SDS... hydrochloride [pH7.5]. 20 mM EDTA, (2 x STE buffer), was used. For electron microscopy pellets were resuspended in 10 mM Tris- hydrochloride [pH 7.5]. 1 inM

Mesolimbic and Nigrostriatal Dopaminergic Systems: Behavioral Neuropharmacology.

DTIC Science & Technology

1985-08-01

presented in Table Table III List of drugs D ru gVeh i c l e Intracerebral infusions Dopamine agonist~s Apomorphine hydrochloride 0.1% Na metabisulfite...saline GABA 0.9% saline Picrotoxin 0 .9%saline Systemic injections Dopamine agents d-Amphetamine sulfate 0.9% saline Aponiorphine hydrochloride 0.9...3H)methionine (15 Ci/mmole, lmCi/ml. 16 Amersham), 122 ul of freshly prepared pargyline hydrochloride (10.2 mM), 326 ul of I M Tris pH 10.8, 246 ul

Effects of Topical Anesthetics on Pullularia pullulans and Debaryomyces hansenii

PubMed Central

Merdinger, Emanuel; Guthmann, Walter S.; Mangine, Francis W.

1969-01-01

The inhibitory effects of three topical anesthetics of various concentrations on the growth of Pullularia pullulans, Debaryomyces hansenii, and on pigment production by P. pullulans were investigated. The topical anesthetics were benoxinate hydrochloride, proparacaine hydrochloride, and tetracaine hydrochloride. In decreasing order, the inhibiting effects of the drugs on growth were benoxinate, tetracaine, and proparacaine for P. pullulans, and tetracaine, benoxinate, and proparacaine for D. hansenii. The pigment formation in P. pullulans was inhibited by the three drugs. PMID:5392897

21 CFR 216.24 - Drug products withdrawn or removed from the market for reasons of safety or effectiveness.

Code of Federal Regulations, 2010 CFR

2010-04-01

... containing metabromsalan. Methamphetamine hydrochloride: All parenteral drug products containing methamphetamine hydrochloride. Methapyrilene: All drug products containing methapyrilene. Methopholine: All drug...

Effects of pilocarpine hydrochloride and cevimeline on submandibular/sublingual salivation in rat xerostomia model produced by X-ray irradiation.

PubMed

Omori, Yasuhiro; Asari, Tetsuya; Maruyama, Kazuyasu; Kusama, Hiroshi; Kojima, Masami; Shibata, Nobuo

2003-01-01

The present study was performed to assess the effects of pilocarpine hydrochloride ((3S,4R)-3-ethyl-dihydro-4-[(1-methyl-1H-imidazole-5-yl)methyl]-2(3H)-furanone monohydrochloride, CAS 54-71-7) and cevimeline ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate, CAS 153504-70-2), muscarinic receptor agonists, on salivary secretion from the submandibular/sublingual (SM/SL) glands in normal rats and in rats with xerostomia induced by X-ray (15 Gy) irradiation. To clarify their pharmacological safety profiles, the two drugs were further compared with regard to subtype selectivity for muscarinic receptors (M1, M2, and M3) and central nervous, respiratory, and cardiovascular effects. Pilocarpine hydrochloride (0.1-0.8 mg/kg i.d.) and cevimeline (3-30 mg/kg i.d.) dose-dependently increased salivary flow rate and total salivary volume in a 120-min period from SM/SL glands in both normal and irradiated rats, the minimum effective doses for their sialagogic effects being 0.2 and 10 mg/kg, respectively. Both drugs also increased protein output from SM/SL glands to a degree that depended on the increase in salivary volume in normal and irradiated rats. In a binding study using radiolabeled antagonists, neither pilocarpine hydrochloride nor cevimeline displayed subtype selectivity for muscarinic receptors, indicating non-selective muscarinic agonism. Effects on the central nervous system (CNS) were assessed by monitoring changes in body temperature in conscious normal rats. Pilocarpine hydrochloride (0.4-4 mg/kg p.o.) had no effect on body temperature, but cevimeline (30 and 100 mg/kg p.o.) caused a significant hypothermia. In terms of respiratory and cardiovascular effects in anesthetized normal rats, there was no clear difference in safety margin between pilocarpine hydrochloride and cevimeline, both drugs inducing significant changes in respiratory rate, heart rate, and blood pressure at doses close to those inducing sialagogic effects. These results suggest that pilocarpine hydrochloride could be used as a sialagogic drug for postirradiation-induced xerostomia with fewer adverse effects on the CNS.

21 CFR 522.723 - Diprenorphine hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Specifications. Each milliliter of diprenorphine hydrochloride injection, veterinary, contains 2 mg of... injection, veterinary, the use of which is provided for in § 522.883, in wild and exotic animals. (2) It is...

Calorimetric, FTIR and 1H NMR measurements in combination with DFT calculations for monitoring solid-state changes of dynamics of sibutramine hydrochloride.

PubMed

Pajzderska, Aleksandra; Chudoba, Dorota M; Mielcarek, Jadwiga; Wąsicki, Jan

2012-10-01

Two forms of sibutramine hydrochloride, monohydrate and anhydrous, have been investigated by calorimetric methods, Fourier transform infrared (FTIR) absorption and (1) H nuclear magnetic resonance (NMR) measurements as well as by density functional theory (DFT) of vibrational frequencies and infrared intensities, calculations of steric hindrances and Monte Carlo simulations. The results of FTIR spectra combined with DFT calculations permitted identification of the bands corresponding to the dynamics and vibrations of water molecules. NMR study and Monte Carlo simulations revealed the occurrence of reorientation jumps of the methyl groups in sibutramine cation and also revealed that the reorientation of isopropyl group is possible only in sibutramine monohydrate hydrochloride. The hydration of sibutramine hydrochloride causes a change in the conformation of sibutramine cation. Copyright © 2012 Wiley-Liss, Inc.

Chemical stability of diphenhydramine hydrochloride from an elixir and lidocaine hydrochloride from a viscous solution when mixed together.

PubMed

Gupta, Vishnu D

2006-01-01

The stability of diphenhydramine hydrochloride (from an elixir) and lidocaine hydrochloride (from a viscous solution) in a mixture (1:1) was studied using a stability-indicating high-peformance liquid chromatographic assay method. The concentrations of the drugs were related directly to peak heights and the percent relative standard deviations based on five injections were 1.4 for diphenhydramine and 1.3 for lidocaine. The products of hydrolysis from the both the drugs and a number of excipients present in the dosage forms did not interfere with the developed assay procedure. The mixture was stable for at least 21 days when stored in amber-colored bottles at room temperature. The pH value of the mixture remained constant, and the physical appearance did not change during the study period.

Validated Colorimetric Assay of Clonidine Hydrochloride from Pharmaceutical Preparations

PubMed Central

Corciova, Andreia

2016-01-01

Clonidine hydrochloride is an antihypertensive agent used for migraine prophylaxis, attention deficit hyperactivity disorder, menopausal flushing and Tourette syndrome. The quantity of the active substance in pharmaceutical preparations must be within specific limits, in agreement with the respective label claim. Therefore, the aim of this study was to establish the conditions for two spectrophotometric methods for clonidine determination, based on the formation of the ion pair complex between clonidine hydrochloride and thymol blue/bromophenol blue. A Jasco UV-Vis 530 spectrophotometer was used for the analysis and the maxim absorbance was measured at 418 nm/448 nm against blank solution. After validation, the methods were used for quantification of clonidine hydrochloride in two commercial samples (tablets). The recovery of active substance varies between 98.06 and 100.13 % without interferences from the excipients. PMID:27610155

Intravesical application of rebamipide promotes urothelial healing in a rat cystitis model.

PubMed

Funahashi, Yasuhito; Yoshida, Masaki; Yamamoto, Tokunori; Majima, Tsuyoshi; Takai, Shun; Gotoh, Momokazu

2014-12-01

Rebamipide is used as a topical therapeutic agent for various organs. We examined the healing effects of intravesical rebamipide on damaged urothelium in a rat model of chemically induced cystitis. Hydrochloride was injected in the bladder of female Sprague Dawley® rats to induce cystitis. On days 1 and 4 rebamipide (1 or 10 mM) or vehicle was administered in the bladder and maintained for 1 hour. Histopathology, urothelial permeability, cystometrogram and nociceptive behaviors were evaluated on day 7. Also, tissue rebamipide concentrations after the 1-hour bladder instillation were quantified using high performance liquid chromatography. Intravesically administered rebamipide permeated the bladder, particularly in hydrochloride treated rats, and the pharmacologically effective tissue dose remained for greater than 6 hours. Bladder histological evaluation revealed polymorphological inflammatory cell infiltration and decreased positive staining for uroplakin 3A in hydrochloride treated rats. Scanning electron microscopy showed damaged tight junctions in the hydrochloride group. Evans blue absorption in the bladder wall was increased in hydrochloride treated rats. These findings, which were associated with urothelial injury and increased permeability, were dependently suppressed by the rebamipide treatment dose. Cystometrogram demonstrated that the intercontraction interval was shorter in hydrochloride treated rats but prolonged by rebamipide. The increased nociceptive behaviors observed after intravesical resiniferatoxin administration were also suppressed by rebamipide. Intravesical rebamipide accelerated the repair of damaged urothelium, protected urothelial barrier function and suppressed bladder overactivity and nociception. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Films based on soy protein-agar blends for wound dressing: Effect of different biopolymer proportions on the drug release rate and the physical and antibacterial properties of the films.

PubMed

Rivadeneira, Josefina; Audisio, M C; Gorustovich, Alejandro

2018-04-01

No single material can provide all requirements for wound dressings. Here, we evaluated the influence of different soy protein isolate and agar proportions (3:1, 1:1, and 1:3) in blend films on some of their physical-chemical and antibacterial properties to elucidate their potential as wound dressings. The films were synthesized by the gel casting method and ciprofloxacin hydrochloride was incorporated into the films. Films were characterized based on their surface morphology, water uptake ability, and weight loss profile. Also, the ciprofloxacin hydrochloride release kinetics was quantified spectrophotometrically. The antibacterial effect was evaluated against Staphylococcus aureus and Pseudomonas aeruginosa strains. The soy protein isolate-agar ratio affected the water uptake of the films and the release profile of ciprofloxacin hydrochloride but not the weight loss profile. The amount of drug released decreased near 80% because of the decrease in agar content in the films. The release kinetics of ciprofloxacin hydrochloride data best fitted to the Korsmeyer-Peppas model, suggesting that the mechanism of drug release was mainly of the diffusion type. All ciprofloxacin hydrochloride-releasing soy protein isolate-agar films strongly inhibited the cell viability of the bacterial strains studied. We concluded that water uptake and ciprofloxacin hydrochloride release can be controlled by changing the soy protein isolate-agar proportion. The proportions did not lead to changes in the antibacterial strength of the films.

Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2007-12-01

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide, Uracil, Ustekinumab; V-260, Vandetanib, Vatalanib succinate, Vernakalant hydrochloride, Vorinostat; YM-155; Zileuton, Zoledronic acid monohydrate.

[Pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in Beagle dogs].

PubMed

Chen, He-Li; Zhang, Wen-Ping; Yang, Fu-Ying; Wang, Xin-Yu; Yang, Wen-Cheng; Dang, Hong-Wan

2013-05-01

The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.

Immediate acid-suppressing effects of ranitidine hydrochloride and rabeprazole sodium following initial administration and reintroduction: A randomized, cross-over study using wireless pH monitoring capsules.

PubMed

Ono, Shouko; Kato, Mototsugu; Ono, Yuji; Imai, Aki; Yoshida, Takeshi; Shimizu, Yuichi; Asaka, Masahiro

2009-04-01

Histamine 2 receptor antagonists and proton-pump inhibitors, drugs that are widely used for the treatment of acid-related diseases, have different clinical characteristics. The objective of this study was to compare the acid-suppressing effects of ranitidine hydrochloride and those of rabeprazole sodium at the first administration and re-administration after withdrawal. The study was designed as an open-label, randomized, two-way cross-over trial. Seven Helicobacter pylori-negative healthy volunteers were enrolled in this study. Ranitidine hydrochloride (300 mg/day) or rabeprazole sodium (20 mg/day) was administered from days 1 to 7 and from days 11 to 13. The percentage of time with gastric pH < 4 and the median gastric pH were evaluated for 15 consecutive days by a Bravo capsule fixed to the stomach. On day 1, there was no significant difference between the acid-suppressing effects of the two drugs (ranitidine vs rabeprazole: not significant). Although rabeprazole sodium maintained a potent and stable effect from days 2 to 7 (ranitidine vs rabeprazole: P < 0.05), the effect of ranitidine hydrochloride was attenuated after day 4. In addition, the effect of ranitidine hydrochloride at re-administration was attenuated (days 11, 12, and 13 vs pre-administration: not significant). In view of our observations, we expect symptoms associated with gastric acidity to be more adequately controlled with rabeprazole sodium in the short term when compared to ranitidine hydrochloride.

Influence of dissolution media pH and USP1 basket speed on erosion and disintegration characteristics of immediate release metformin hydrochloride tablets.

PubMed

Desai, Divyakant; Wong, Benjamin; Huang, Yande; Tang, Dan; Hemenway, Jeffrey; Paruchuri, Srinivasa; Guo, Hang; Hsieh, Daniel; Timmins, Peter

2015-01-01

To investigate the influence of the pH of the dissolution medium on immediate release 850 mg metformin hydrochloride tablets. A traditional wet granulation method was used to manufacture metformin hydrochloride tablets with or without a disintegrant. Tablet dissolution was conducted using the USP apparatus I at 100 rpm. In spite of its pH-independent high solubility, metformin hydrochloride tablets dissolved significantly slower in 0.1 N HCl (pH 1.2) and 50 mM pH 4.5 acetate buffer compared with 50 mM pH 6.8 phosphate buffer, the dissolution medium in the USP. Metformin hydrochloride API compressed into a round 1200 mg disk showed a similar trend. When basket rotation speed was increased from 100 to 250 rpm, the dissolution of metformin hydrochloride tablets was similar in all three media. Incorporation of 2% w/w crospovidone in the tablet formulation improved the dissolution although the pH-dependent trend was still evident, but incorporation of 2% w/w croscarmellose sodium resulted in rapid pH-independent tablet dissolution. In absence of a disintegrant in the tablet formulation, the dissolution was governed by the erosion-diffusion process. Even for a highly soluble drug, a super-disintegrant was needed in the formulation to overcome the diffusion layer limitation and change the dissolution mechanism from erosion-diffusion to disintegration.

Conditioned place avoidance of zebrafish (Danio rerio) to three chemicals used for euthanasia and anaesthesia.

PubMed

Wong, Devina; von Keyserlingk, Marina A G; Richards, Jeffrey G; Weary, Daniel M

2014-01-01

Zebrafish are becoming one of the most used vertebrates in developmental and biomedical research. Fish are commonly killed at the end of an experiment with an overdose of tricaine methanesulfonate (TMS, also known as MS-222), but to date little research has assessed if exposure to this or other agents qualifies as euthanasia (i.e. a "good death"). Alternative agents include metomidate hydrochloride and clove oil. We use a conditioned place avoidance paradigm to compare aversion to TMS, clove oil, and metomidate hydrochloride. Zebrafish (n = 51) were exposed to the different anaesthetics in the initially preferred side of a light/dark box. After exposure to TMS zebrafish spent less time in their previously preferred side; aversion was less pronounced following exposure to metomidate hydrochloride and clove oil. Nine of 17 fish exposed to TMS chose not to re-enter the previously preferred side, versus 2 of 18 and 3 of 16 refusals for metomidate hydrochloride and clove oil, respectively. We conclude that metomidate hydrochloride and clove oil are less aversive than TMS and that these agents be used as humane alternatives to TMS for killing zebrafish.

New drugs of 2003.

PubMed

Hussar, Daniel A

2004-01-01

To provide information regarding the most important properties of the new therapeutic agents marketed in 2003. Product labeling supplemented selectively with published studies and drug information reference sources. By the author. By the author. The 28 new therapeutic agents marketed in the United States during 2003 are reviewed in this article: adalimumab, agalsidase beta, alefacept, alfuzosin hydrochloride, aprepitant, atazanavir sulfate, atomoxetine hydrochloride, bortezomib, daptomycin, efalizumab, eletriptan hydrobromide, emtricitabine, enfuvirtide, eplerenone, gefitinib, icodextrin, laronidase, memantine hydrochloride, mequinol/tretinoin, miglustat, nitazoxanide, omalizumab, palonosetron hydrochloride, pegvisomant, rosuvastatin calcium, tadalafil, tositumomab and iodine I 131 tositumomab, and vardenafil hydrochloride. Indications and information on dosage and administration for these agents are reviewed, as are the most important pharmacokinetic properties, adverse events, drug interactions, and other precautions. Practical considerations for the use of the new agents are also discussed. When possible, the properties of the new drugs are compared with those of older drugs marketed for the same indications. A number of the new therapeutic agents marketed in 2003 have important advantages over older medications. An understanding of the properties of these agents is important for the pharmacist to effectively counsel patients about their use and to serve as a valuable source of information for other health professionals regarding these drugs.

Effects of itopride hydrochloride and ranitidine in patients with functional dyspepsia: comparison between prokinetic and acid suppression therapies.

PubMed

Chiba, Toshimi; Tokunaga, Yumi; Ikeda, Keisei; Takagi, Ryo; Chishima, Raita; Terui, Torahiko; Kudara, Norihiko; Endo, Masaki; Inomata, Masaaki; Orii, Seishi; Suzuki, Kazuyuki

2007-09-01

The effect of itopride hydrochloride or ranitidine on the health-related quality of life (HRQoL) of functional dyspepsia is not well known. Our aim was to assess the HRQoL before and after administration of itopride hydrochloride or ranitidine in patients with functional dyspepsia. A total of 18 functional dyspepsia patients (12 women, 6 men; mean age 52.5 y.o.) were enrolled. We determined the HRQoL using two different inquiry systems: the 36 item short form of the Medical Outcome Study Questionnaire (SF-36) and the Gastrointestinal Symptom Rating Scale (GSRS). The HRQoL was determined before administration of drug, and two, four, and eight weeks after administration of drug. After administration of itopride hydrochloride, the SF-36 mental health scale and GSRS indigestion syndrome score and constipation syndrome score were significantly improved compared to before administration (p < 0.05). After the administration of ranitidine, the GSRS reflux syndrome score was significantly improved compared to before administration (p < 0.05). Itopride hydrochloride would be useful for the treatment of dysmotility-type functional dyspepsia, whereas ranitidine would be beneficial for ulcer-type functional dyspepsia.

Optimization of Robust HPLC Method for Quantitation of Ambroxol Hydrochloride and Roxithromycin Using a DoE Approach.

PubMed

Patel, Rashmin B; Patel, Nilay M; Patel, Mrunali R; Solanki, Ajay B

2017-03-01

The aim of this work was to develop and optimize a robust HPLC method for the separation and quantitation of ambroxol hydrochloride and roxithromycin utilizing Design of Experiment (DoE) approach. The Plackett-Burman design was used to assess the impact of independent variables (concentration of organic phase, mobile phase pH, flow rate and column temperature) on peak resolution, USP tailing and number of plates. A central composite design was utilized to evaluate the main, interaction, and quadratic effects of independent variables on the selected dependent variables. The optimized HPLC method was validated based on ICH Q2R1 guideline and was used to separate and quantify ambroxol hydrochloride and roxithromycin in tablet formulations. The findings showed that DoE approach could be effectively applied to optimize a robust HPLC method for quantification of ambroxol hydrochloride and roxithromycin in tablet formulations. Statistical comparison between results of proposed and reported HPLC method revealed no significant difference; indicating the ability of proposed HPLC method for analysis of ambroxol hydrochloride and roxithromycin in pharmaceutical formulations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Niosomal encapsulation of ethambutol hydrochloride for increasing its efficacy and safety.

PubMed

El-Ridy, Mohammed Shafik; Yehia, Soad Aly; Kassem, Mahfouz Abd-El-Megeid; Mostafa, Dina Mahmoud; Nasr, Essam Amin; Asfour, Marwa Hasanin

2015-01-01

Tuberculosis (TB) is a worldwide health concern. In 2011, about 8.7 million new cases developed TB and 1.4 million people died from it. Enhancement of ethambutol hydrochloride activity and safety in treatment of TB through niosomal encapsulation. Niosomes were prepared by the thin-film hydration method. They were characterized, investigated for in vitro release, lung disposition and in vivo biological evaluation. Entrapment efficiency of ethambutol hydrochloride ranged from 12.20% to 25.81%. Zeta potential values inferred stability of neutral and negatively charged formulations. In vitro release was biphasic. Lung targeting was increased by niosomal encapsulation. Biological evaluation revealed superiority of niosomal ethambutol hydrochloride over the free drug. Neutral and negatively charged niosomal vesicles are dispersed homogenously unlike positively charged vesicles. Niosomal encapsulation results in controlled drug release. Niosomal formulations targeted more drugs to mice lungs for a prolonged period of time resulting in: decreased root-specific lung weight, bacterial counts in lung homogenates and optimizing pathological effect on guinea pigs lungs, livers and spleens. Encapsulation of ethambutol hydrochloride in niosomal formulations for the treatment of TB provides higher efficacy and safety compared with the free drug.

[Clinical observation of icotinib hydrochloride for patients with advanced non-small cell lung cancer].

PubMed

Li, Xi; Yang, Xin-jie; Sun, Yi-fen; Qin, Na; Lü, Jia-lin; Wu, Yu-hua; Zhang, Hui; Zhang, Quan; Zhang, Shu-cai

2012-08-01

To explore the efficacy and side effects of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The efficacy and side effects of icotinib hydrochloride in treatment of 59 cases with stage IV NSCIC and followed-up from March 2009 to January 2012 were retrospectively analyzed. Twenty seven patients (45.8%) showed partial response (PR), 17 patients (28.8%) achieved SD, and 15 (25.4%) had progressive disease. The objective response rate (ORR) was 45.8% (27/59), and disease control rate (DCR) was 74.6% (44/59). Among the 23 patients with EGFR mutation, ORR was 73.9% (17/23), and DCR was 95.7% (22/23). Thirty six patients (61.0%) achieved remission of symptoms to varying degrees. The main symptoms relieved were cough, asthmatic suffocating, pain and hoarseness. The major adverse events were mild skin rash (35.6%) and diarrhea (15.3%). Others were dry skin, nausea and stomach problems. The efficacy of icotinib hydrochloride were related to the ECOG performance status, smoking history, EGFR mutation and rash significantly (P < 0.05). Monotherapy with icotinib hydrochloride is effective and tolerable for patients with advanced NSCLC, especially with EGFR mutation.

New thermoresistant polymorph from CO2 recrystallization of minocycline hydrochloride.

PubMed

Rodrigues, Miguel A; Tiago, João M; Padrela, Luis; Matos, Henrique A; Nunes, Teresa G; Pinheiro, Lídia; Almeida, António J; de Azevedo, Edmundo Gomes

2014-11-01

To prepare and thoroughly characterize a new polymorph of the broad-spectrum antibiotic minocycline from its hydrochloride dehydrate salts. The new minocycline hydrochloride polymorph was prepared by means of the antisolvent effect caused by carbon dioxide. Minocycline recrystallized as a red crystalline hydrochloride salt, starting from solutions or suspensions containing CO2 and ethanol under defined conditions of temperature, pressure and composition. This novel polymorph (β-minocycline) revealed characteristic PXRD and FTIR patterns and a high melting point (of 247 ºC) compared to the initial minocycline hydrochloride hydrates (α-minocycline). Upon dissolution the new polymorph showed full anti-microbial activity. Solid-state NMR and DSC studies evidenced the higher chemical stability and crystalline homogeneity of β-minocycline compared to the commercial chlorohydrate powders. Molecular structures of both minocyclines present relevant differences as shown by multinuclear solid-state NMR. This work describes a new crystalline structure of minocycline and evidences the ability of ethanol-CO2 system in removing water molecules from the crystalline structure of this API, at modest pressure, temperature and relatively short time (2 h), while controlling the crystal habit. This process has therefore the potential to become a consistent alternative towards the control of the solid form of APIs.

21 CFR 522.1335 - Medetomidine hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... solution contains 1.0 milligram of medetomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of... diseases, dogs in shock, dogs which are severly debilitated, or dogs which are stressed due to extreme heat...

21 CFR 522.1335 - Medetomidine hydrochloride injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... solution contains 1.0 milligram of medetomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of... diseases, dogs in shock, dogs which are severly debilitated, or dogs which are stressed due to extreme heat...

21 CFR 522.1335 - Medetomidine hydrochloride injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... solution contains 1.0 milligram of medetomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of... diseases, dogs in shock, dogs which are severly debilitated, or dogs which are stressed due to extreme heat...

21 CFR 522.1335 - Medetomidine hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... solution contains 1.0 milligram of medetomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of... diseases, dogs in shock, dogs which are severly debilitated, or dogs which are stressed due to extreme heat...

21 CFR 184.1676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... hydrochloride that is prepared by chemical synthesis. (b) The ingredient meets the specifications of the Food...)(31) of this chapter; plant protein products as defined in § 170.3(n)(33) of this chapter; and snack...

Comparative Pharmacodynamics and Plasma Concentrations of D-Threo-Methylphenidate Hydrochloride after Single Doses of D-Threo-Methylphenidate Hydrochloride and D,l-Threo-Methylphenidate Hydrochloride in a Double-Blind, Placebo-Controlled, Crossover Laboratory School Study in Children with Attention-Deficit/hyperactivity Disorder

ERIC Educational Resources Information Center

Quinn, Declan; Wigal, Sharon; Swanson, James; Hirsch, Sharon; Ottolini, Yvonne; Dariani, Maghsoud; Roffman, Mark; Zeldis, Jerome; Cooper, Thomas

2004-01-01

Objective: Methylphenidate has four optical isomers due to two asymmetries (erythro-threo and dextro-levo). The initial commercial formulation eliminated the erythro isomer, but the dextro-levo asymmetry was racemic, with equal amounts of d and l-threo isomers (d,l-MPH). Previous work has suggested that the d-threo isomer methylphenidate (d-MPH)…

Inhibitory gene expression of the Cav3.1 T-type calcium channel to improve neuronal injury induced by lidocaine hydrochloride.

PubMed

Wen, Xianjie; Xu, Shiyuan; Zhang, Qingguo; Li, Xiaohong; Liang, Hua; Yang, Chenxiang; Wang, Hanbing; Liu, Hongzhen

2016-03-15

Cav3.1 is a low-voltage-activated (LVA) calcium channel that plays a key role in regulating intracellular calcium ion levels. In this study, we observed the effects of lidocaine hydrochloride on the pshRNA-CACNA1G-SH-SY5Y cells that silenced Cav3.1 mRNA by RNA interference, and investigated the roles of p38 MAPK in these effects. We constructed the pNC-puro-CACNA1G-SH-SY5Y cells and pshRNA-CACNA1G -SH-SY5Y cells by the RNA interference. All the cells were cultured with or without 10mM lidocaine hydrochloride for 24 h. The cell morphology, cell viability, Cav3.1 and p38 protein expression, cell apoptosis rate and intracellular calcium ion concentration were detected. We found that all cells treated with 10mM lidocaine hydrochloride for 24 h showed cellular rounding, axonal regression, and cellular floating. Compared with the cells in SH-SY5Y+Lido group and NC+Lido group, those in the RNAi+Lido group showed similar changes, but of smaller magnitude. Additionally, following lidocaine hydrochloride all cells displayed increased Cav3.1 and p38 MAPK protein, apoptosis rate, and intracellular calcium ion levels; however,these changes in the RNAi+Lido group were less pronounced than in the SH-SY5Y+Lido and NC+Lido groups. The cell viability decreased following lidocaine hydrochloride treatment, but viability of the cells in the RNAi+Lido group was higher than in the SH-SY5Y+Lido and NC+Lido groups. The results showed that Cav3.1 may be involved in neuronal injury induced by lidocaine hydrochloride and that p38 MAPK phosphorylation was reduced upon Cav3.1 gene silencing. Copyright © 2016 Elsevier B.V. All rights reserved.

Immobilization of free-ranging maned wolf (Chrysocyon brachyurus) with tiletamine and zolazepam in central Brazil.

PubMed

Furtado, Mariana Malzoni; Kashivakura, Cynthia Kayo; Ferro, Claudia; de Almeida, Jácomo Anah Tereza; Silveira, Leandro; Astete, Samuel

2006-03-01

A tiletamine hydrochloride-zolazepam hydrochloride combination was used successfully to immobilize 27 free-ranging maned wolves (Chrysocyon brachyurus) at a mean dose of 2.77+/-0.56 (mean+/-SD) mg/kg. The induction time ranged from 3-15 min. Animals remained immobilized for periods of 48.56 +/-12.65 min. Compulsive licking, excessive salivation, muscle twitching, muscle tremors, tachypnea, and bradycardia were observed associated with the induction of the anesthesia in 13 of 27 maned wolves. Muscle twitching, pedal withdrawal reflex, muscle tremors, and ataxia were observed during recovery in three (11%) maned wolves. There were no significant differences in heart rates (P = 0.44), respiratory rates (P = 0.82), and rectal temperatures (P = 0.54) recorded at 5, 15, and 25 min after induction at these dosages. The tiletamine hydrochloride-zolazepam hydrochloride combination was shown to be an effective and safe immobilizing agent for free-ranging maned wolves.

Use of xylazine hydrochloride-ketamine hydrochloride for immobilization of wild leopards (Panthera pardus fusca) in emergency situations.

PubMed

Belsare, Aniruddha V; Athreya, Vidya R

2010-06-01

In India, leopards (Panthera pardus fusca) inhabit human-dominated landscapes, resulting in encounters that require interventions to prevent harm to people, as well as the leopards. Immobilization is a prerequisite for any such intervention. Such emergency field immobilizations have to be carried out with limited tools, often amidst large uncontrollable crowds. An effective and practicable approach is discussed, based on 55 wild leopard immobilizations undertaken between January 2003 and April 2008. A xylazine hydrochloride (1.4 +/- 0.3 mg/kg)--ketamine hydrochloride (5 +/- 2 mg/kg) mixture was used for immobilization of leopards, based on estimated body weight. When weight could not be estimated, a standard initial dose of 50 mg of xylazine--150 mg of ketamine was used. Supplemental doses (50-75 mg) of only ketamine were used as required. No life-threatening adverse effects of immobilization were documented for at least 1 mo postimmobilization.

Synthesis, spectral, and anti-microbial studies of thioiminium iodides and amine hydrochlorides.

PubMed

Britto, Sebastian; Renaud, Philippe; Nallu, Maruthai

2014-01-01

To avoid the undesired deprotonation during the addition of organolithium and organomagnesium reagents to ketones, the thioiminium salts, easily prepared from lactams and amides are converted into 2,2-disubstituted and 2-monosubstituted amines by reaction with simple nucleophiles such as organocerium and organocopper reagents. The reaction of thioiminium iodides with organocerium reagents derived by transmetalation of corresponding lithium reagents with anhydrous cerium(III) chloride has been investigated. These thioiminium iodides act as good electrophiles and accept alkylceriums towards bisaddition. The newly synthesized amines have been characterized by 1H and 13C NMR, IR and mass spectra. The amines have been converted into their hydrochlorides and characterized by COSY. These hydrochlorides have been subjected to antimicrobial screening with clinically isolated microorganisms, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi and Candida albicans. The hydrochlorides show quite good activity against these bacteria and fungus. Copyright © 2013 Elsevier B.V. All rights reserved.

Colestipol hydrochloride prophylaxis of diarrhea during pelvic radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stryker, J.A.; Chung, C.K.; Layser, J.D.

1983-02-01

Thirty-three patients were randomized prior to pelvic radiotherapy to receive the bile acid-sequestering resin colestipol hydrochloride, 5 grams qid, during the entire time of their therapy or diphenoxylate hydrochloride and atropine sulfate 2.5-20 mg per day (control) if they experienced diarrhea. The colestipol patients also took diphenoxylate if they had diarrhea. The patients in the colestipol group often experienced nausea, vomiting, and abdominal cramps and 8 were forced to discontinue the drug. There was no difference in the weekly stool frequency between the colestipol and the control patients but the colestipol patients who took at least 50% of the prescribedmore » dose required fewer diphenoxylate tablets than the controls. The data suggest that colestipol hydrochloride is not of value in preventing radiation-induced diarrhea because of the side effects associated with the drug, but the theory on which the use of bile acid-sequestering agents is based may be correct.« less

Health and environmental effects profile for 2,4-dimethylaniline and 2,4-dimethylaniline hydrochloride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1987-01-01

The Health and Environmental Effects Profile for 2-4-Dimethylaniline and 2,4-Dimethylaniline Hydrochloride was prepared to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained from Agency program office files were evaluated as they pertained to potential human-health, aquatic-life and environmental effects of hazardous-waste constituents. The human carcinogen potency factors (q1*) for 2-4-dimethylaniline and 2,4-dimethylaniline hydrochloride are 0.75 and 0.58/(mg/kg/day) respectively,more » for oral exposure. The Reportable Quantity (RQ) value for 2-4-dimethylaniline and 2,4-dimethylaniline Hydrochloride is 1000.« less

Health and environmental effects profile for 4-chloro-2-methylaniline and 4-chloro-2-methylaniline hydrochloride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1986-12-01

The Health and Environmental Effects Profile for 4-chloro-2-methylaniline and 4-chloro-2-methylaniline hydrochloride was prepared to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained from Agency program office files were evaluated as they pertained to potential human-health, aquatic-life and environmental effects of hazardous-waste constituents. The human carcinogen potency factors (q1*) for 4-chloro-2-methylaniline and 4-chloro-2-methylaniline hydrochloride are 0.58 and 0.46/(mg/kg/day), respectively,more » for oral exposure. The Reportable Quantity (RQ) value for 4-chloro-2-methylaniline and 4-chloro-2-methylaniline hydrochloride is 5000.« less

In vitro and in vivo genotoxicity assessment of the dopamine receptor antagonist molindone hydrochloride.

PubMed

Krishna, Gopala; Gopalakrishnan, Gopa; Goel, Saryu

2016-05-01

Molindone hydrochloride is a dihydroindolone neuroleptic with dopamine D2 and D5 receptor antagonist activity. As an integral component of its preclinical safety evaluation, molindone hydrochloride was evaluated in a series of in vitro and in vivo genetic toxicology assays. In the bacterial reverse gene mutation assays employing four Salmonella tester strains (TA98, TA100, TA1535, and TA1537) and the E. coli tester strain WP2uvrA, molindone hydrochloride was negative in all strains, except TA100, in which it induced a positive response (up to 3-fold) in the presence of rat liver S9. With human S9, a small (2-fold), but nonreproducible, increase in revertants was observed in TA100 at the highest concentration of molindone tested (5,000 µg/plate). The mutagenicity was completely abrogated by the addition of glutathione and UDP-glucuronic acid to rat liver S9, suggesting detoxification of the mutagenic metabolite(s) by Phase II conjugation reactions, pathways commonly operational in humans. Molindone hydrochloride did not induce chromosomal aberrations in human lymphocyte cultures, did not elicit a positive response in a rat bone marrow micronucleus test for clastogencity/aneugenicity, and did not give a positive response in the rat liver comet assay for DNA damage. Collectively, the weight of evidence from these studies, combined with a large margin of safety and efficient detoxification through Phase II conjugation supports the interpretation that molindone hydrochloride does not pose a genotoxic risk to humans at the anticipated clinical dose levels. © 2016 Wiley Periodicals, Inc.

Optimization of mesoporous carbons for efficient adsorption of berberine hydrochloride from aqueous solutions.

PubMed

Li, Yin; Fu, Jie; Deng, Shuguang; Lu, Xiuyang

2014-06-15

Sixteen mesoporous carbon adsorbents were synthesized by varying the ratio of soft to hard templates in order to optimize the pore textural properties of these adsorbents. The mesoporous carbon adsorbents have a high BET specific surface area (1590.3-2193.5 m(2)/g), large pore volume (1.72-2.56 cm(3)/g), and uniform pore size distribution with a median pore diameter ranging from 3.51 nm to 4.52 nm. It was observed that pore textural properties of the carbon adsorbents critically depend on the molar ratio of carbon sources to templates, and the hard template plays a more important role than the soft template in manipulating the pore textures. Adsorption isotherms of berberine hydrochloride at 303 K were measured to evaluate the adsorption efficacy of these adsorbents. The adsorption of berberine hydrochloride from aqueous solutions on the sixteen mesoporous carbon adsorbents synthesized in this work is very efficient, and the adsorption equilibrium capacities on all samples are more than double the adsorption capacities of berberine hydrochloride of the benchmark adsorbents (polymer resins and spherical activated carbons) at similar conditions. It was observed from the adsorption experiments that the equilibrium adsorption amounts of berberine hydrochloride are strongly correlated with the BET specific surface area and pore volume of the adsorbents. The adsorbent with the highest BET of 2193.5 m(2)/g displayed the largest adsorption capacity of 574 mg/g at an equilibrium concentration of 0.10mg/mL of berberine hydrochloride in an aqueous solution. Copyright © 2014 Elsevier Inc. All rights reserved.

Preparation and the in vitro evaluation of nanoemulsion system for the transdermal delivery of granisetron hydrochloride.

PubMed

Zheng, Wen-wu; Zhao, Ling; Wei, Yu-meng; Ye, Yun; Xiao, Shun-han

2010-08-01

The objective of this study was to develop and evaluate nanoemulsion system for transdermal delivery of granisetron hydrochloride. Pseudo-ternary phase diagram was constructed to ascertain the concentration range of components of nanoemulsion composed of isopropyl myristate (IPM) as an oil phase, tween 85 as surfactant, ethanol as cosurfactant, water as aqueous phase. The effects of the content of IPM as an oil phase and n-methyl pyrrolidone (NMP) as transdermal enhancer on rat skin permeation of granisetron hydrochloride nanoemulsion were studied in vitro. The results showed that the mean particle size of nanoemulsion ranged from 50.4+/-1.5 to 82.4+/-0.9 nm with homogeneous size distribution. The resulted optimum formulation composed of 2.5% granisetron hydrochloride, 4% IPM, 40% tween 85/ethanol (1 : 1) and 10% NMP showed that the skin permeation rate was the highest (85.39+/-2.90 microg/cm(2)/h) and enhancement of drug permeability was 4.1-fold for transdermal delivery of granisetron hydrochloridein comparison with the control group (20% of tween 85 and 20% of ethanol micelle solution containing 2.5% of granisetron hydrochloride without IPM), and cumulative permeation amount was the highest (891.8+/-2.86 microg/cm(2)) with the shortest lag time (0.11+/-0.02 h) and was stable for at least 12 months. Therefore, the nanoemulsion system developed in this study offers a promising vehicle for the transdermal delivery system of granisetron hydrochloride, which may be as effective as oral or intravenous dosage forms and avoid some difficulties associated with these dosage forms.

Antinociceptive effects after oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Sanchez-Migallon Guzman, David; Souza, Marcy J; Braun, Jana M; Cox, Sherry K; Keuler, Nicholas S; Paul-Murphy, Joanne R

2012-08-01

To evaluate antinociceptive effects on thermal thresholds after oral administration of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-15 healthy adult Hispaniolan Amazon parrots. 2 crossover experiments were conducted. In the first experiment, 15 parrots received 3 treatments (tramadol at 2 doses [10 and 20 mg/kg] and a control suspension) administered orally. In the second experiment, 11 parrots received 2 treatments (tramadol hydrochloride [30 mg/kg] and a control suspension) administered orally. Baseline thermal foot withdrawal threshold was measured 1 hour before drug or control suspension administration; thermal foot withdrawal threshold was measured after administration at 0.5, 1.5, 3, and 6 hours (both experiments) and also at 9 hours (second experiment only). For the first experiment, there were no overall effects of treatment, hour, period, or any interactions. For the second experiment, there was an overall effect of treatment, with a significant difference between tramadol hydrochloride and control suspension (mean change from baseline, 2.00° and -0.09°C, respectively). There also was a significant change from baseline for tramadol hydrochloride at 0.5, 1.5, and 6 hours after administration but not at 3 or 9 hours after administration. Tramadol at a dose of 30 mg/kg, PO, induced thermal antinociception in Hispaniolan Amazon parrots. This dose was necessary for induction of significant and sustained analgesic effects, with duration of action up to 6 hours. Further studies with other types of noxious stimulation, dosages, and intervals are needed to fully evaluate the analgesic effects of tramadol hydrochloride in psittacines.

Accelerometric comparison of the locomotor pattern of horses sedated with xylazine hydrochloride, detomidine hydrochloride, or romifidine hydrochloride.

PubMed

López-Sanromán, F Javier; Holmbak-Petersen, Ronald; Varela, Marta; del Alamo, Ana M; Santiago, Isabel

2013-06-01

To evaluate the duration of effects on movement patterns of horses after sedation with equipotent doses of xylazine hydrochloride, detomidine hydrochloride, or romifidine hydrochloride and determine whether accelerometry can be used to quantify differences among drug treatments. 6 healthy horses. Each horse was injected IV with saline (0.9% NaCl) solution (10 mL), xylazine diluted in saline solution (0.5 mg/kg), detomidine diluted in saline solution (0.01 mg/kg), or romifidine diluted in saline solution (0.04 mg/kg) in random order. A triaxial accelerometric device was used for gait assessment 15 minutes before and 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after each treatment. Eight variables were calculated, including speed, stride frequency, stride length, regularity, dorsoventral power, propulsive power, mediolateral power, and total power; the force of acceleration and 3 components of power were then calculated. Significant differences were evident in stride frequency and regularity between treatments with saline solution and each α2-adrenoceptor agonist drug; in speed, dorsoventral power, propulsive power, total power, and force values between treatments with saline solution and detomidine or romifidine; and in mediolateral power between treatments with saline solution and detomidine. Stride length did not differ among treatments. Accelerometric evaluation of horses administered α2-adrenoceptor agonist drugs revealed more prolonged sedative effects of romifidine, compared with effects of xylazine or detomidine. Accelerometry could be useful in assessing the effects of other sedatives and analgesics. Accelerometric data may be helpful in drug selection for situations in which a horse's balance and coordination are important.

Comparison of Clinical Efficacies of Preoperatively Initiated Naproxen Sodium-Codeine Phosphate in Combination, Diclofenac Potassium, and Benzydamine Hydrochloride for Pain, Edema, and Trismus After Extraction of Impacted Lower Third Molar: A Randomized Double-Blind Study.

PubMed

Cigerim, Levent; Eroglu, Cennet Neslihan

2018-03-01

The aim of this study was to compare the clinical efficacies of naproxen sodium-codeine phosphate in combination, benzydamine hydrochloride, and diclofenac potassium for pain, edema, and trismus after lower third molar extraction. Ninety healthy volunteers in whom impacted third molar extraction was indicated were randomly distributed into 3 groups. One hour before the tooth-extraction process, patients were administered one of the following drugs: naproxen sodium, 550 mg, and codeine phosphate, 30 mg, in a tablet; diclofenac potassium, 50 mg, in a coated pill; or benzydamine hydrochloride, 50 mg, in a coated pill. Pain assessment was conducted via a visual analog scale; edema assessment, by measuring the distances between predetermined facial landmarks; and trismus assessment, by measuring interincisal distance. Regarding rescue analgesics (paracetamol, 500 mg), the number and time of use by patients were recorded. Naproxen sodium-codeine phosphate was more effective for pain, edema, and trismus than diclofenac potassium and benzydamine hydrochloride (P < .05). Benzydamine hydrochloride yielded similar clinical responses to diclofenac potassium (P > .05). No drug-related side effects were observed. Naproxen sodium-codeine phosphate constitutes the drug of choice after the extraction of a patient's impacted lower third molar. Benzydamine hydrochloride has similar efficacy to diclofenac potassium, and it can be used as a nonsteroidal anti-inflammatory analgesic drug. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Insecticide toxicity to the borer Neoleucinodes elegantalis (Guenée) (Lepidoptera: Crambidae): developmental and egg-laying effects.

PubMed

Silva, R S; Arcanjo, L P; Soares, J R S; Ferreira, D O; Serrão, J E; Martins, J C; Costa, Á H; Picanço, M C

2018-04-01

Neoleucinodes elegantalis (Guenée) (Lepidoptera: Crambidae) is one of the major pests of solanaceous plants in South America. It is considered a great threat by the European and Mediterranean Plant Protection Organization due to the serious economic damage that it causes on tomato farms; therefore, controlling this pest is a challenging task in South America. Controlling N. elegantalis at the egg stage is the best way to prevent it from damaging crops; however, thorough studies about the effectiveness of chemicals on the different life stages of this insect pest are lacking. In this study, the effects of different chemical classes were evaluated on N. elegantalis adults, female oviposition behavior, larvae, eggs, and embryonic development. None of the tested insecticides demonstrated toxicity to the adults; however, the results showed that cartap hydrochloride affects oviposition behavior. Moreover, methomyl and cartap hydrochloride exhibited high toxicity against the eggs and larvae, with higher than 80% of mortality. These insecticides interrupted larval hatching and caused alterations in the chorion layer. Flubendiamide and deltamethrin demonstrated toxicity on N. elegantalis larvae; however, lufenuron, indoxacarb, methoxyfenozide, and chlorantraniliprole demonstrated low toxicity on both eggs and larvae, with lower than 70% of mortality. Fruit treated with cartap hydrochloride had a deterrent effect. The ovicidal activity revealed by methomyl and cartap hydrochloride might provide new approaches regarding insecticide effects on eggs. Methomyl, cartap hydrochloride, flubendiamide, and deltamethrin demonstrated toxicity on larvae. The evaluation of the chorion of the eggshell in this study has clarified the toxic effect of methomyl and cartap hydrochloride on eggs.

A novel, molecularly imprinted polymer sensor made using an oligomeric methyl silsesquioxane-TiO2 composite sol on a glassy carbon electrode for the detection of procainamide hydrochloride.

PubMed

Wang, Kai; Guan, Xiwen; Chai, Shigan; Zou, Qichao; Zhang, Xiuhua; Zhang, Jinzhi

2015-02-15

In this study, we designed a novel molecularly imprinted polymer (MIP), oligomeric methyl silsesquioxane (O-MSSQ)-TiO2 composite sol, which was made using a sol-gel reaction. This polymer has structural rigidity and high surface area of O-MSSQ, as well as high bio-compatibility and relatively good conductivity of the TiO2. Next, a sensitive and selective imprinted electrochemical sensor was successfully constructed for the direct detection of procainamide hydrochloride by molecularly imprinting a film onto the surface of a glassy carbon electrode. Adding TiO2 resulted in a noticeable enhancement in the sensitivity of the MIP sensor. The performance of the O-MSSQ-TiO2 film was discussed, and the optimal conditions for detection were determined. The oxidative peak current increased linearly with the concentration of procainamide hydrochloride in the range of 4.00 × 10(-9)-4.97 × 10(-5) M using differential pulse voltammetry, and the detection limit was 1.30 × 10(-9) M with S/N = 3. Furthermore, the sensor was applied to determine the procainamide hydrochloride content in a human blood serum sample. The recoveries of the sensors varied from 96.77% to 101.35%, indicating that the prepared sensor might be promising for the determination of procainamide hydrochloride in clinical tests. Moreover, the imprinted electrochemical sensor was used to selectively detect procainamide hydrochloride. The analytical application was conducted successfully and yielded accurate and precise results. Copyright © 2014 Elsevier B.V. All rights reserved.

Toxicity of naproxen sodium and its mixture with tramadol hydrochloride on fish early life stages.

PubMed

Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Fiorino, Emma; Faggio, Caterina; Svobodova, Zdenka

2017-12-01

Pharmaceuticals occur in water bodies as a consequence of their incomplete removal during waste water treatment processes. The occurence of pharmaceuticals in surface waters as well as their possible impact on aquatic vertebrates have received considerable attention in recent years. However, there is still a lack of informations on the chronic effects of widely used drugs as well as their possible mixture toxicity on non-target aquatic vertebrates as well as their possible mixture toxicity. The aim of this study was to assess the effects of naproxen sodium on early life stages of fish and evaluate its mixture toxicity with tramadol hydrochloride, which was assessed in our earlier study as a single substance. Two embryo-larval toxicity tests with common carp (Cyprinus carpio) were performed according to the OECD guideline 210 (Fish, Early-life Stage Toxicity Test) in order to assess the subchronic toxicity of naproxen sodium and tramadol hydrochlorid-naproxen sodium mixture at the concentrations of 10; 50; 100 and 200 μg/L. These experiments were conducted for 32 days. The subchronic exposure to naproxen sodium and naproxen sodium and tramadol hydrochloride mixture had a strong effect on the early life stages of common carp. Hatching, developmental rate, morphology, histopathology and, in the case of the naproxen sodium and tramadol hydrochloride mixture, mortality were influenced. The bioindicators of oxidative stress were also influenced. The LOEC was determined at 10 μg/L for both naproxen sodium and naproxen sodium and tramadol hydrochloride mixture. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development and Validation of a Rapid RP-UPLC Method for the Simultaneous Estimation of Bambuterol Hydrochloride and Montelukast Sodium from Tablets

PubMed Central

Yanamandra, R.; Vadla, C. S.; Puppala, U. M.; Patro, B.; Murthy, Y. L. N.; Parimi, A. R.

2012-01-01

A rapid, simple, sensitive and selective analytical method was developed by using reverse phase ultra performance liquid chromatographic technique for the simultaneous estimation of bambuterol hydrochloride and montelukast sodium in combined tablet dosage form. The developed method is superior in technology to conventional high performance liquid chromatography with respect to speed, resolution, solvent consumption, time, and cost of analysis. Elution time for the separation was 6 min and ultra violet detection was carried out at 210 nm. Efficient separation was achieved on BEH C18 sub-2-μm Acquity UPLC column using 0.025% (v/v) trifluoro acetic acid in water and acetonitrile as organic solvent in a linear gradient program. Resolutions between bambuterol hydrochloride and montelukast sodium were found to be more than 31. The active pharmaceutical ingredient was extracted from tablet dosage from using a mixture of methanol, acetonitrile and water as diluent. The calibration graphs were linear for bambuterol hydrochloride and montelukast sodium in the range of 6.25-37.5 μg/ml. The percentage recoveries for bambuterol hydrochloride and montelukast sodium were found to be in the range of 99.1-100.0% and 98.0-101.6%, respectively. The test solution was found to be stable for 7 days when stored in the refrigerator between 2-8°. Developed UPLC method was validated as per International Conference on Harmonization specifications for method validation. This method can be successfully employed for simultaneous estimation of bambuterol hydrochloride and montelukast sodium in bulk drugs and formulations. PMID:23325991

Fundamentals of ionic conductivity relaxation gained from study of procaine hydrochloride and procainamide hydrochloride at ambient and elevated pressure.

PubMed

Wojnarowska, Z; Swiety-Pospiech, A; Grzybowska, K; Hawelek, L; Paluch, M; Ngai, K L

2012-04-28

The pharmaceuticals, procaine hydrochloride and procainamide hydrochloride, are glass-forming as well as ionically conducting materials. We have made dielectric measurements at ambient and elevated pressures to characterize the dynamics of the ion conductivity relaxation in these pharmaceuticals, and calorimetric measurements for the structural relaxation. Perhaps due to their special chemical and physical structures, novel features are found in the ionic conductivity relaxation of these pharmaceuticals. Data of conductivity relaxation in most ionic conductors when represented by the electric loss modulus usually show a single resolved peak in the electric modulus loss M(")(f) spectra. However, in procaine hydrochloride and procainamide hydrochloride we find in addition another resolved loss peak at higher frequencies over a temperature range spanning across T(g). The situation is analogous to many non-ionic glass-formers showing the presence of the structural α-relaxation together with the Johari-Goldstein (JG) β-relaxation. Naturally the analogy leads us to name the slower and faster processes resolved in procaine hydrochloride and procainamide hydrochloride as the primary α-conductivity relaxation and the secondary β-conductivity relaxation, respectively. The analogy of the β-conductivity relaxation in procaine HCl and procainamide HCl with JG β-relaxation in non-ionic glass-formers goes further by the finding that the β-conductivity is strongly related to the α-conductivity relaxation at temperatures above and below T(g). At elevated pressure but compensated by raising temperature to maintain α-conductivity relaxation time constant, the data show invariance of the ratio between the β- and the α-conductivity relaxation times to changes of thermodynamic condition. This property indicates that the β-conductivity relaxation has fundamental importance and is indispensable as the precursor of the α-conductivity relaxation, analogous to the relation found between the Johari-Goldstein β-relaxation and the structural α-relaxation in non-ionic glass-forming systems. The novel features of the ionic conductivity relaxation are brought out by presenting the measurements in terms of the electric modulus or permittivity. If presented in terms of conductivity, the novel features are lost. This warns against insisting that a log-log plot of conductivity vs. frequency is optimal to reveal and interpret the dynamics of ionic conductors.

40 CFR 180.499 - Propamocarb hydrochloride, tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for residues. 180.499 Section 180.499 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.499 Propamocarb hydrochloride, tolerances for residues. (a) General. Tolerances are...

40 CFR 180.499 - Propamocarb hydrochloride, tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... for residues. 180.499 Section 180.499 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.499 Propamocarb hydrochloride, tolerances for residues. (a) General. Tolerances are...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grachev, S.A.; Chakchir, B.A.; Ryabykh, L.D.

The feasibility of radiation sterilization was studied on ephedrine hydrochloride, atropine sulfate, scopolamine hydrobromide, strychnine nitrate, morphine hydrochloride, codeine phosphate, proserine, cysteamine hydrochloride, and unithiol in form of injectable solutions and as powders. It was shown that the sterilizing dose of radioactivity results in a breakdown of the solutions as shown by changes in the pH, color, and loss of biological activity. Alkaloid powders exhibited no changes after radiation sterilization. Deaerated solutions were also stable to the radiation but such solutions could not be prepared easily under industrial conditions. Temperature had no effect on the stability of test samples exceptmore » for very low temperatures. (JPRS)« less

Analysis of volatile organic compounds from illicit cocaine samples

NASA Astrophysics Data System (ADS)

Robins, W. H.; Wright, Bob W.

1994-10-01

Detection of illicit cocaine hydrochloride shipments can be improved if there is a greater understanding of the identity and quantity of volatile compounds present. This study provides preliminary data concerning the volatile organic compounds detected in a limited set of cocaine hydrochloride samples. In all cases, cocaine was one of the major volatile compounds detected. Other tropeines were detected in almost all samples. Low concentrations of compounds which may be residues of processing solvents were observed in some samples. The equilibrium emissivity of cocaine from cocaine hydrochloride was investigated and a value of 83 parts-per-trillion was determined.

Bioavailability of paracetamol, phenylephrine hydrochloride and guaifenesin in a fixed-combination syrup versus an oral reference product.

PubMed

Janin, Annick; Monnet, Joelle

2014-04-01

The primary objective of this study was to compare the bioavailability of paracetamol, phenylephrine hydrochloride and guaifenesin in a new oral syrup with an established oral reference product. The secondary objective was to compare the safety of the new syrup and the reference product. This was a single-centre, open-label, randomized, reference-replicated, crossover study. Healthy adult volunteers received one dose of syrup and two separate doses of a reference oral liquid formulation in a randomized sequence over three study periods, with a washout interval of ≥ 7 days between study periods. Blood samples were taken regularly postdose and analysed for paracetamol, phenylephrine hydrochloride and guaifenesin concentrations; adverse events were recorded. This study enrolled 45 subjects. For paracetamol and guaifenesin, the syrup and reference product were considered to be bioequivalent. Bioequivalence was not shown for phenylephrine hydrochloride. All adverse events were mild or moderate, most of which were considered formulation related. The syrup did not reach bioequivalence with the reference product, as bioequivalence could not be shown for phenylephrine hydrochloride. This may be due to differences in the excipients between the two products. Both the syrup and the reference product had a good safety profile and were well tolerated.

Use of an in vitro human skin permeation assay to assess bioequivalence of two topical cream formulations containing butenafine hydrochloride (1%, w/w).

PubMed

Mitra, Amitava; Kim, Nanhye; Spark, Darren; Toner, Frank; Craig, Susan; Roper, Clive; Meyer, Thomas A

2016-12-01

The primary objective of this work was to investigate, using an in vitro human skin permeation study, whether changes in the excipients of butenafine hydrochloride cream would have any effect on bioperformance of the formulation. Such in vitro data would be a surrogate for any requirement of a bioequivalence (BE) study to demonstrate formulation similarity. A LC-MS/MS method for quantitation of butenafine in various matrices was developed and validated. A pilot study was performed to validate the in vitro skin permeation methodology using three cream formulations containing butenafine hydrochloride at concentrations of 0.5, 1.0 and 1.5% (w/w). Finally, a definitive in vitro human skin permeation study was conducted, comparing the extent of butenafine hydrochloride permeation from the new formulation to that from the current formulation. The results of the study comparing the two formulations showed that there was no statistically significant difference in the extent of butenafine permeation into human skin. In conclusion, these in vitro data demonstrated that the formulation change is likely to have no significant impact on the bioperformance of 1% (w/w) butenafine hydrochloride cream. Copyright © 2016 Elsevier Inc. All rights reserved.

Intradermal bacteriostatic 0.9% sodium chloride containing the preservative benzyl alcohol compared with intradermal lidocaine hydrochloride 1% for attenuation of intravenous cannulation pain.

PubMed

McNelis, K A

1998-12-01

This study compared the efficacy of a common medication diluent, bacteriostatic 0.9% sodium chloride containing the preservative benzyl alcohol with lidocaine hydrochloride 1% as an intradermal pretreatment for the relief of pain associated with intravenous cannulation. Forty adult presurgical patients requiring two large bore intravenous catheters were used. They served as their own controls. The inner aspect of one forearm received the usual pretreatment, lidocaine hydrochloride 1%, and the inner aspect of the opposite arm received intradermal pretreatment with bacteriostatic 0.9% sodium chloride with the preservative benzyl alcohol. Intravenous cannulation was accomplished on the first attempt, and pain reported with cannulation was rated using a visual analogue scale (VAS). A paired t test was used to compare differences in VAS scores with the pretreatment bacteriostatic 0.9% sodium chloride containing the preservative benzyl alcohol with the pretreatment lidocaine hydrochloride 1%. Analysis of the data revealed no significant difference in the report of perceived pain of intravenous cannulation based on the intradermal pretreatment. These findings suggest that intradermal bacteriostatic 0.9% sodium chloride containing the preservative benzyl alcohol is as effective as intradermal lidocaine hydrochloride 1% in the attenuation of intravenous cannulation pain.

Development and validation of a reversed-phase HPLC method for simultaneous estimation of ambroxol hydrochloride and azithromycin in tablet dosage form.

PubMed

Shaikh, K A; Patil, S D; Devkhile, A B

2008-12-15

A simple, precise and accurate reversed-phase liquid chromatographic method has been developed for the simultaneous estimation of ambroxol hydrochloride and azithromycin in tablet formulations. The chromatographic separation was achieved on a Xterra RP18 (250 mm x 4.6 mm, 5 microm) analytical column. A Mixture of acetonitrile-dipotassium phosphate (30 mM) (50:50, v/v) (pH 9.0) was used as the mobile phase, at a flow rate of 1.7 ml/min and detector wavelength at 215 nm. The retention time of ambroxol and azithromycin was found to be 5.0 and 11.5 min, respectively. The validation of the proposed method was carried out for specificity, linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. The linear dynamic ranges were from 30-180 to 250-1500 microg/ml for ambroxol hydrochloride and azithromycin, respectively. The percentage recovery obtained for ambroxol hydrochloride and azithromycin were 99.40 and 99.90%, respectively. Limit of detection and quantification for azithromycin were 0.8 and 2.3 microg/ml, for ambroxol hydrochloride 0.004 and 0.01 microg/ml, respectively. The developed method can be used for routine quality control analysis of titled drugs in combination in tablet formulation.

[Simultaneous determination of scopolamine hydrobromide, atropine sulfate, ephedrine hydrochloride and pseudoephedrine hydrochloride in Zhichuanling oral liquid with HPLC].

PubMed

Zhang, Yu-Lin; Li, Yu-Ping

2013-10-01

To establish an HPLC method for determining the contents of scopolamine hydrobromide, atropine sulfate, ephedrine hydrochloride and pseudoephedrine hydrochloride in Zhichuanling oral liquid. Agela Durashell RP-C18 (4. 6 mm x250 mm, 5 microm) was adopted, with acetonitrile-sodium phosphate buffer solution (0. 07 mol L-1 sodium phosphate solution with 17.5 mmol L-1 sodium dodecylsulfate adjusted to pH 6.0 with phosphoric acid solution) (30:70) as the mobile phase. The flow rate was 0. 9 mL min -1, the detection wavelength was 207 nm, and the column temperature was 25 degree C. Scopolamine hydrobromide, atropine sulfate, ephedrine hlvdrochloride and pseudoephedrine hydrochloride showed good linear relations with peak areas within the concentration range of 0. 021 21-1. 060 5 pg (r =0. 999 3) , 0. 011 14-0. 557 microg (r = 0. 999 6) , 0. 200 56-10. 028 microg (r =0. 999 7) and 0.070 33-3. 516 5 gg (r =0. 999 6), respectively, with the average recoveries of 101.9% , 99. 80%, 100. 3%, 100. 2% (n=6). The method was so quick, simple, highly reproducible and specific that it could be used as one of quality control methods of Zhichuanling oral liquid.

Determination of metformin hydrochloride and glyburide in an antihyperglycemic binary mixture using high-performance liquid chromatographic-UV and spectrometric methods.

PubMed

Salem, Hesham

2010-01-01

Three methods were developed for simultaneous determination of metformin hydrochloride and glyburide in an antihyperglycemic binary mixture without previous separation. In the first method, a reversed-phase HPLC column with acetonitrile-water (60 + 40, v/v) mobile phase at 0.9 mL/min flow rate was used to separate both compounds, with UV detection at 254 nm. Linearity was obtained in the concentration range of 0.06--0.24 microg/mL for glyburide and 1.5-6.0 microg/mL for metformin hydrochloride. The second method depended on first- and second-derivative UV spectrometry with zero-crossing measurements. The first-derivative amplitude at 261 nm was selected for the assay of glyburide, and the second-derivative amplitude at 235 nm was selected for the assay of metformin hydrochloride. The third method depended on measuring the first derivative of the ratio-spectra at 241 nm for glyburide and 227 nm for metformin hydrochloride. For the second and third methods, Beer's law was obeyed in the range of 10-55 microg/mL for glyburide and 20-200 microg/mL for metformin. The proposed methods were extensively validated and applied for the analysis of some pharmaceutical formulations containing binary mixtures of the mentioned drugs.

Investigation of the Atypical Glass Transition and Recrystallization Behavior of Amorphous Prazosin Salts

PubMed Central

Kumar, Lokesh; Popat, Dharmesh; Bansal, Arvind K.

2011-01-01

This manuscript studied the effect of counterion on the glass transition and recrystallization behavior of amorphous salts of prazosin. Three amorphous salts of prazosin, namely, prazosin hydrochloride, prazosin mesylate and prazosin tosylate were prepared by spray drying, and characterized by optical-polarized microscopy, differential scanning calorimetry and powder X-ray diffraction. Modulated differential scanning calorimetry was used to determine the glass transition and recrystallization temperature of amorphous salts. Glass transition of amorphous salts followed the order: prazosin mesylate > prazosin tosylate ∼ prazosin hydrochloride. Amorphous prazosin mesylate and prazosin tosylate showed glass transition, followed by recrystallization. In contrast, amorphous prazosin hydrochloride showed glass transition and recrystallization simultaneously. Density Functional Theory, however, suggested the expected order of glass transition as prazosin hydrochloride > prazosin mesylate > prazosin tosylate. The counterintuitive observation of amorphous prazosin hydrochloride having lower glass transition was explained in terms of its lower activation energy (206.1 kJ/mol) for molecular mobility at Tg, compared to that for amorphous prazosin mesylate (448.5 kJ/mol) and prazosin tosylate (490.7 kJ/mol), and was further correlated to a difference in hydrogen bonding strength of the amorphous and the corresponding recrystallized salts. This study has implications in selection of an optimal amorphous salt form for pharmaceutical development. PMID:24310595

Investigation of the atypical glass transition and recrystallization behavior of amorphous prazosin salts.

PubMed

Kumar, Lokesh; Popat, Dharmesh; Bansal, Arvind K

2011-08-25

This manuscript studied the effect of counterion on the glass transition and recrystallization behavior of amorphous salts of prazosin. Three amorphous salts of prazosin, namely, prazosin hydrochloride, prazosin mesylate and prazosin tosylate were prepared by spray drying, and characterized by optical-polarized microscopy, differential scanning calorimetry and powder X-ray diffraction. Modulated differential scanning calorimetry was used to determine the glass transition and recrystallization temperature of amorphous salts. Glass transition of amorphous salts followed the order: prazosin mesylate > prazosin tosylate ~ prazosin hydrochloride. Amorphous prazosin mesylate and prazosin tosylate showed glass transition, followed by recrystallization. In contrast, amorphous prazosin hydrochloride showed glass transition and recrystallization simultaneously. Density Functional Theory, however, suggested the expected order of glass transition as prazosin hydrochloride > prazosin mesylate > prazosin tosylate. The counterintuitive observation of amorphous prazosin hydrochloride having lower glass transition was explained in terms of its lower activation energy (206.1 kJ/mol) for molecular mobility at Tg, compared to that for amorphous prazosin mesylate (448.5 kJ/mol) and prazosin tosylate (490.7 kJ/mol), and was further correlated to a difference in hydrogen bonding strength of the amorphous and the corresponding recrystallized salts. This study has implications in selection of an optimal amorphous salt form for pharmaceutical development.

NTP toxicity studies of dimethylaminopropyl chloride, hydrochloride (CAS No. 5407-04-5) administered by Gavage to F344/N rats and B6C3F1 mice.

PubMed

Abdo, Km

2007-07-01

Dimethylaminopropyl chloride, hydrochloride is used primarily as an industrial and research organic chemical intermediate acting as an alkylating reagent in Grignard and other types of reactions. It is also used as a pharmaceutical intermediate for the synthesis of many types of drugs, as an agricultural chemical intermediate, as a photographic chemical intermediate, and as a biochemical reagent for enzyme and other studies. Human occupational or other accidental exposure can occur by inhalation, ingestion, or skin absorption. Male and female F344/N rats and B6C3F1 mice received dimethylaminopropyl chloride, hydrochloride (greater than 99% pure) in water by gavage for 2 weeks or 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. In the 2-week toxicity studies, groups of five male and five female F344/N rats and B6C3F1 mice were administered doses of 0, 6.25, 12.5, 25, 50, or 100 mg dimethylaminopropyl chloride, hydrochloride/kg body weight in deionized water by gavage, 5 days per week for 16 days. All dosed male and female rats and mice survived until the end of the 2-week study; one vehicle control female mouse died early. Mean body weights of all dosed groups of rats and mice were similar to those of the vehicle control groups. No gross or microscopic lesions were considered related to dimethylaminopropyl chloride, hydrochloride administration. In the 3-month toxicity studies, groups of 10 male and 10 female F344/N rats and B6C3F1 mice were administered doses of 0, 6.25, 12.5, 25, 50, or 100 mg/kg in deionized water by gavage, 5 days per week for 3 months. One male rat in the 50 mg/kg group died during week 12 of the study, and one female mouse in the 100 mg/kg group died during week 9 and another during week 13. The final mean body weights of 50 mg/kg male rats and 50 mg/kg female mice were significantly less than those of the vehicle controls. Possible chemical-related clinical findings in rats included lethargy in one 50 mg/kg male and one 100 mg/kg male, tremors in one 100 mg/kg male, and ataxia in one 50 mg/kg male and two 100 mg/kg males. Absolute lung weights in the 25, 50, and 100 mg/kg groups of female mice were significantly less than those of the vehicle controls. Total serum bile acid concentrations were increased in 50 mg/kg male rats and 100 mg/kg male and female rats. The incidence of goblet cell hypertrophy of the nose was significantly increased in 100 mg/kg male rats compared to the vehicle controls. There were no significant histopathologic findings in mice. Dimethylaminopropyl chloride, hydrochloride was mutagenic in the Salmonella typhimurium base substitution strains TA100 and TA1535, with and without hamster or rat liver S9 activation enzymes; no mutagenic activity was seen in TA97 or TA98. No increase in the frequency of micronucleated erythrocytes was seen in peripheral blood of male or female mice administered dimethylaminopropyl chloride, hydrochloride for 3 months by gavage. In summary, dimethylaminopropyl chloride, hydrochloride caused increased incidences of goblet cell hypertrophy in the nose of male rats and increased serum bile acid concentrations in male and female rats. In mice, dimethylaminopropyl chloride, hydrochloride caused deaths in females administered 100 mg/kg. The estimated no-observed-effect levels were 50 mg/kg per day for male rats and female mice, 100 to 200 mg/kg per day for female rats, and greater than 100 mg/kg per day for male mice. Synonyms: 3-Chloropropyldimethyl-ammonium chloride; (3-chloropropyl)dimethylamine, hydrochloride; N-(3-chloropropyl)-N,N-dimethylammonium chloride; 3-dimethylamino-1-propyl chloride hydrochloride; 3-dimethylaminopropyl chloride hydrochloride; DMPC; 1-propylamine, 3-chloro-N,N-dimethyl-, hydrochloride.

21 CFR 556.580 - Robenidine hydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.580 Robenidine hydrochloride. Tolerances are established...

21 CFR 556.580 - Robenidine hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.580 Robenidine hydrochloride. Tolerances are established...

21 CFR 556.580 - Robenidine hydrochloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.580 Robenidine hydrochloride. Tolerances are established...

21 CFR 556.580 - Robenidine hydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.580 Robenidine hydrochloride. Tolerances are established...

21 CFR 556.580 - Robenidine hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.580 Robenidine hydrochloride. Tolerances are established...

Development of Novel Potentiometric Sensors for Determination of Lidocaine Hydrochloride in Pharmaceutical Preparations, Serum and Urine Samples

PubMed Central

Ali, Tamer Awad; Mohamed, Gehad Genidy; Yahya, Ghada A.

2017-01-01

This article is focused on the determination of lidocaine hydrochloride as a local anaesthetic drug. A potentiometric method based on modified screen-printed and modified carbon paste ion-selective electrodes was described for the determination of lidocaine hydrochloride in different pharmaceutical preparations and biological fluids (urine and serum). It was based on potentiometric titration of lidocaine hydrochloride using modified screen-printed and carbon paste electrodes as end point indicator sensors. The influences of the paste composition, different conditioning parameters and foreign ions on the electrodes performance were investigated and response times of the electrodes were studied. The electrodes showed Nernstian response of 58.9 and 57.5 mV decade-1 in the concentration range of 1×10-7–1×10-2 and 6.2×10-7–1×10-2 mol L-1 for modified screen-printed and carbon paste electrodes, respectively. The electrodes were found to be usable within the pH range of 2.0–8.0 and 2.0-7.5, exhibited a fast response time (about 6 and 4) low detection limit (1×10-7 and 6.2×10-7 mol L-1), long lifetime (6 and 4 months) and good stability for modified screen-printed (Electrode VII) and carbon paste electrodes (Electrode III), respectively. The electrodes were successfully applied for the determination of lidocaine hydrochloride in pure solutions, pharmaceutical preparation and biological fluids (urine and serum) samples. The results obtained applying these potentiometric electrodes were comparable with British pharmacopeia. The method validation parameters were optimized and the method can be applied for routine analysis of lidocaine hydrochloride drug. PMID:28979305

Development of Novel Potentiometric Sensors for Determination of Lidocaine Hydrochloride in Pharmaceutical Preparations, Serum and Urine Samples.

PubMed

Ali, Tamer Awad; Mohamed, Gehad Genidy; Yahya, Ghada A

2017-01-01

This article is focused on the determination of lidocaine hydrochloride as a local anaesthetic drug. A potentiometric method based on modified screen-printed and modified carbon paste ion-selective electrodes was described for the determination of lidocaine hydrochloride in different pharmaceutical preparations and biological fluids (urine and serum). It was based on potentiometric titration of lidocaine hydrochloride using modified screen-printed and carbon paste electrodes as end point indicator sensors. The influences of the paste composition, different conditioning parameters and foreign ions on the electrodes performance were investigated and response times of the electrodes were studied. The electrodes showed Nernstian response of 58.9 and 57.5 mV decade -1 in the concentration range of 1×10 -7 -1×10 -2 and 6.2×10 -7 -1×10 -2 mol L -1 for modified screen-printed and carbon paste electrodes, respectively. The electrodes were found to be usable within the pH range of 2.0-8.0 and 2.0-7.5, exhibited a fast response time (about 6 and 4) low detection limit (1×10 -7 and 6.2×10 -7 mol L -1 ), long lifetime (6 and 4 months) and good stability for modified screen-printed (Electrode VII) and carbon paste electrodes (Electrode III), respectively. The electrodes were successfully applied for the determination of lidocaine hydrochloride in pure solutions, pharmaceutical preparation and biological fluids (urine and serum) samples. The results obtained applying these potentiometric electrodes were comparable with British pharmacopeia. The method validation parameters were optimized and the method can be applied for routine analysis of lidocaine hydrochloride drug.

Influence of Polymer Type on the Physical Properties and Release Profile of Papaverine Hydrochloride From Hard Gelatin Capsules.

PubMed

Polski, Andrzej; Iwaniak, Karol; Kasperek, Regina; Modrzewska, Joanna; Sobótka-Polska, Karolina; Sławińska, Karolina; Poleszak, Ewa

2015-01-01

The capsule is one of the most important solid dosage forms in the pharmaceutical industry. It is easier and faster to produce than a tablet, because it requires fewer excipients. Generally, capsules are easy to swallow and mask any unpleasant taste of the substances used while their release profiles can be easily modified. Papaverine hydrochloride was used as a model substance to show different release profiles using different excipients. The main aim of the study was to analyze the impact of using different polymers on the release profile of papaverine hydrochloride from hard gelatin capsules. Six series of hard gelatin capsules containing papaverine hydrochloride as a model drug and different excipients were made. Then, the angle of repose, flow rate, mass flow rate and volume flow rate of the powders used for capsule production were analyzed. The uniform weight and disintegration time of the capsules were studied. The dissolution study was performed in a basket apparatus, while the amount of papaverine hydrochloride released was determined spectrophotometrically at 251 nm. Only one formula of powder had satisfactory flow properties, while all formulas had good Hausner ratios. The best properties were from powder containing polyvinylpyrrolidone 10k. The disintegration time of capsules varied from 1:30 min to 2:00 min. As required by Polish Pharmacopoeia X, 80% of the active substance in all cases was released within 15 minutes. The capsules with polyvinylpyrrolidone 10k were characterized by the longest release. On the other hand, capsules containing microcrystalline cellulose had the fastest release profile. Using 10% of different polymers, without changing the other excipients, had a significant impact on the physical properties of the powders and papaverine hydrochloride release profile. The two most preferred capsule formulations contained either polyvinylpyrrolidone 10k or microcrystalline cellulose.

Pharmacokinetics of Lidocaine Hydrochloride Metabolized by CYP3A4 in Chinese Han Volunteers Living at Low Altitude and in Native Han and Tibetan Chinese Volunteers Living at High Altitude.

PubMed

Zhang, Juanling; Zhu, Junbo; Yao, Xingchen; Duan, Yabin; Zhou, Xuejiao; Yang, Meng; Li, Xiangyang

2016-01-01

To investigate the pharmacokinetics of lidocaine hydrochloride metabolized by cytochrome P450 3A4 (CYP3A4) in Chinese Han volunteers living at low altitude (LA) and in native Han and Tibetan Chinese volunteers living at high altitude, lidocaine hydrochloride 10 mg was given by intramuscular injection to 3 groups: Han volunteers living at LA, and native Han and Tibetan volunteers living at a high altitude. Blood samples were collected before the (baseline) study drug was given and at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 h after study drug administration. Lidocaine hydrochloride in plasma was determined by RP-HPLC. Pharmacokinetics parameters of lidocaine hydrochloride showed that there were no significant difference between the native Han and Tibetan volunteers, but the t(1/2) was 29.8 and 29.8% higher in 2 groups, respectively, than in the LA group. To study related mechanism, the effects of exposure to chronic high-altitude hypoxia (CHH) on the activity and expression of CYP3A1 were examined in rats. Rats were divided into LA, chronic moderate altitude hypoxia, and CHH groups. CHH caused significant decreases in the activity and protein and mRNA expression of rat CYP3A1 in vivo. This study found significant changes in the disposition of lidocaine hydrochloride in native healthy Tibetan and Han Chinese subjects living at a high altitude in comparison to healthy Han Chinese subjects living at LA, it might be due to significant decreases in the activity and protein and mRNA expression of CYP3A4 under CHH condition. © 2016 S. Karger AG, Basel.

The effects of ropivacaine hydrochloride on the expression of CaMK II mRNA in the dorsal root ganglion neurons.

PubMed

Wen, Xianjie; Lai, Xiaohong; Li, Xiaohong; Zhang, Tao; Liang, Hua

2016-12-01

In this study, we identified the subtype of Calcium/calmodulin-dependent protein kinase II (CaMK II) mRNA in dorsal root ganglion neurons and observed the effects of ropivacaine hydrochloride in different concentration and different exposure time on the mRNA expression. Dorsal root ganglion neurons were isolated from the SD rats and cultured in vitro. The mRNA of the CaMK II subtype in dorsal root ganglion neurons were detected by real-time PCR. As well as, the dorsal root ganglion neurons were treated with ropivacaine hydrochloride in different concentration (1mM,2mM, 3mM and 4mM) for the same exposure time of 4h, or different exposure time (0h,2h,3h,4h and 6h) at the same concentration(3mM). The changes of the mRNA expression of the CaMK II subtype were observed with real-time PCR. All subtype mRNA of the CaMK II, CaMK II α , CaMK II β , CaMK II δ , CaMK II γ , can be detected in dorsal root ganglion neurons. With the increased of the concentration and exposure time of the ropivacaine hydrochloride, all the subtype mRNA expression increased. Ropivacaine hydrochloride up-regulate the CaMK II β , CaMK II δ , CaMK II g mRNA expression with the concentration and exposure time increasing. The nerve blocking or the neurotoxicity of the ropivacaine hydrochloride maybe involved with CaMK II. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A novel drug delivery gel of terbinafine hydrochloride with high penetration for external use.

PubMed

Yang, Yan; Ou, Rujing; Guan, Shixia; Ye, Xiaoling; Hu, Bo; Zhang, Yi; Lu, Shufan; Zhou, Yubin; Yuan, Zhongwen; Zhang, Jun; Li, Qing-Guo

2015-12-01

Terbinafine hydrochloride is an antifungal drug for onychomycosis. Poor permeability of its external preparation leads to poor curative effect. Transfersomes, also known as flexible liposome, could improve transmission of drug for local external use. Terbinafine hydrochloride-loaded liposome is expected to become a breakthrough on the treatment of onychomycosis. This study is aimed to prepare high skin penetration terbinafine hydrochloride transfersomes with high encapsulation efficiency, appropriate drug loading and good stability. Taking entrapment efficiency as the main indicator, the formulations and the processes of preparation were investigated. Transfersomes with different surfactants were prepared in the optimization processes, and the formulations were optimized through the transdermal test in vitro. As a result, a gel contained transfersomes was obtained with a brief evaluation. Its pharmacokinetic properties of going through the skin were studied by using the micro dialysis technology and liquid chromatography-mass spectrometry to assay the penetration behavior of terbinafine. Mean particle size of the terbinafine hydrochloride transfersomes was 69.6 ± 1.23 nm, and the entrapment efficiency was 95.4% ± 0.51. The content of the gel was 4.45 ± 0.15 mg/g. The accumulated permeation of the transfersomes gel in 12 h was 88.52 ± 4.06 µg cm -2 and the intracutaneous drug detention was 94.38 ± 5.26 µg cm -2 . The results of pharmacokinetic studies showed the C max and area under the curve (AUC) were apparently higher than the commercial cream. The terbinafine hydrochloride transfersomes was highly absorbed by the skin. The absorption rate was significantly higher than that of the commercial cream either in the transdermal test in vitro or in the pharmacokinetic studies in vivo.

Stability of midazolam hydrochloride injection 1-mg/mL solutions in polyvinyl chloride and polyolefin bags.

PubMed

Karlage, Kelly; Earhart, Zachary; Green-Boesen, Kelly; Myrdal, Paul B

2011-08-15

The stability of midazolam hydrochloride injection 1-mg/mL solutions in polyvinyl chloride (PVC) and polyolefin bags under varying conditions was evaluated. Triplicate solutions of midazolam hydrochloride 1-mg/mL were prepared in polyolefin and PVC i.v. bags by diluting midazolam hydrochloride injection 5 mg/mL with 5% dextrose injection. Bags were then stored under refrigeration (3-4 °C), exposed to light at room temperature (20-25 °C), or protected from light in amber bags at room temperature. Samples were taken immediately after preparation (day 0) and on days 1, 2, 3, 6, 13, 20, and 27 for analysis with a stability-indicating high-performance liquid chromatography assay in order to determine solution concentration. Stability was defined as retention of at least 90% of the initial drug concentration. The pH of each solution was also measured weekly. Sterility of the i.v. bags was determined at the end of the study by microbiological testing with culture in growth media. Differences in concentrations under the various storage conditions and bags used were analyzed using analysis of variance. All solutions retained over 98% of the initial midazolam hydrochloride concentration, with no statistically significant (p ≥ 0.05) change in concentration over the four-week period. Stability was not affected by temperature, exposure to light, or bag type. The pH of all solutions remained between 3.2 and 3.4 throughout the study. Sterility after 28 days was retained. Midazolam hydrochloride 1-mg/mL solutions diluted in 5% dextrose injection remained stable over 27 days in both polyolefin and PVC i.v. bags, regardless of storage condition.

Stability studies of lincomycin hydrochloride in aqueous solution and intravenous infusion fluids.

PubMed

Czarniak, Petra; Boddy, Michael; Sunderland, Bruce; Hughes, Jeff D

2016-01-01

The purpose of this study was to evaluate the chemical stability of Lincocin(®) (lincomycin hydrochloride) in commonly used intravenous fluids at room temperature (25°C), at accelerated-degradation temperatures and in selected buffer solutions. The stability of Lincocin(®) injection (containing lincomycin 600 mg/2 mL as the hydrochloride) stored at 25°C±0.1°C in sodium lactate (Hartmann's), 0.9% sodium chloride, 5% glucose, and 10% glucose solutions was investigated over 31 days. Forced degradation of Lincocin(®) in hydrochloric acid, sodium hydroxide, and hydrogen peroxide was performed at 60°C. The effect of pH on the degradation rate of lincomycin hydrochloride stored at 80°C was determined. Lincomycin hydrochloride w as found to maintain its shelf life at 25°C in sodium lactate (Hartmann's) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution, with less than 5% lincomycin degradation occurring in all intravenous solutions over a 31-day period. Lincomycin hydrochloride showed less rapid degradation at 60°C in acid than in basic solution, but degraded rapidly in hydrogen peroxide. At all pH values tested, lincomycin followed first-order kinetics. It had the greatest stability near pH 4 when stored at 80°C (calculated shelf life of 4.59 days), and was least stable at pH 2 (calculated shelf life of 0.38 days). Lincocin(®) injection was chemically found to have a shelf life of at least 31 days at 25°C when added to sodium lactate (Hartmann's) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution. Solutions prepared at approximately pH 4 are likely to have optimum stability.

Amides and Hydrazides from Amine and Hydrazine Hydrochlorides.

ERIC Educational Resources Information Center

Shama, Sami A.; Tran, Thuan L.

1978-01-01

This safe and efficient procedure for the synthesis of N-substituted amides and hydrazides is a modification of the Schotten-Bausmann procedure in which the amine or hydrazide is replaced by the corresponding hydrochloride salt, and the use of alkali is eliminated. (Author/BB)

21 CFR 582.5676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Pyridoxine hydrochloride. 582.5676 Section 582.5676 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

21 CFR 582.5676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Pyridoxine hydrochloride. 582.5676 Section 582.5676 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

21 CFR 582.5676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Pyridoxine hydrochloride. 582.5676 Section 582.5676 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

21 CFR 582.5676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Pyridoxine hydrochloride. 582.5676 Section 582.5676 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

21 CFR 582.5676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Pyridoxine hydrochloride. 582.5676 Section 582.5676 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or...

Dasatinib and Gemcitabine Hydrochloride or Gemcitabine Hydrochloride Alone in Treating Patients With Pancreatic Cancer Previously Treated With Surgery

ClinicalTrials.gov

2018-01-05

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

Development of ligustrazine hydrochloride carboxymethyl chitosan and collagen microspheres: Formulation optimization, characterization, and vitro release

PubMed Central

Lin, Qiang; Huo, Qing; Qin, Yingzhe; Zhao, Zhuo; Tao, Fengyun

2017-01-01

ABSTRACT This study investigates the preparation of ligustrazine hydrochloride carboxymethyl chitosan and collagen microspheres. This experiment investigates effects of the ratio of carboxymethyl chitosan and collagen blend, water to oil ratio, stirring speed, and other factors on the microsphere properties. The experiment had the following conditions: a 1:2 proportion of carboxymethyl chitosan and collagen, a 1:2 proportion of drugs and materials, a 5:1 proportion of oil phase and water phase, 0.5% of span80, a 600r/min stirring speed, 3 ml of a cross-linking agent, 3 h of cross-linking curing, 1.25 ± 0.05 mm diameter LTH microcapsules, a 54.08% envelop rate, and a 14.16% carrier rate. The microspheres release rate reached 66% within 1 h, then steadily released within 5 h in vitro. The experimental results showed that the ligustrazine hydrochloride microsphere production process was stable and exhibited a good release effect compared with other ligustrazine hydrochloride tablets and pills. PMID:27689792

A novel kind of TSV slurry with guanidine hydrochloride

NASA Astrophysics Data System (ADS)

Jiao, Hong; Yuling, Liu; Baoguo, Zhang; Xinhuan, Niu; Liying, Han

2015-10-01

The effect of a novel alkaline TSV (through-silicon-via) slurry with guanidine hydrochloride (GH) on CMP (chemical mechanical polishing) was investigated. The novel alkaline TSV slurry was free of any inhibitors. During the polishing process, the guanidine hydrochloride serves as an effective surface-complexing agent for TSV CMP applications, the removal rate of barrier (Ti) can be chemically controlled through tuned selectivity with respect to the removal rate of copper and dielectric, which is helpful to modifying the dishing and gaining an excellent topography performance in TSV manufacturing. In this paper, we mainly studied the working mechanism of the components of slurry and the skillful application guanidine hydrochloride in the TSV slurry. Project supported by the Major National Science and Technology Special Projects (No. 2009ZX02308), the Fund Project of Hebei Provincial Department of Education, China (No. QN2014208), the Natural Science Foundation of Hebei Province, China (No. E2013202247), and Colleges and Universities Scientific research project of Hebei Province, China (No. Z2014088).

A novel spectrofluorimetric method for the assay of pseudoephedrine hydrochloride in pharmaceutical formulations via derivatization with 4-chloro-7-nitrobenzofurazan.

PubMed

El-Didamony, Akram M; Gouda, Ayman A

2011-01-01

A new highly sensitive and specific spectrofluorimetric method has been developed to determine a sympathomimetic drug pseudoephedrine hydrochloride. The present method was based on derivatization with 4-chloro-7-nitrobenzofurazan in phosphate buffer at pH 7.8 to produce a highly fluorescent product which was measured at 532 nm (excitation at 475 nm). Under the optimized conditions a linear relationship and good correlation was found between the fluorescence intensity and pseudoephedrine hydrochloride concentration in the range of 0.5-5 µg mL(-1). The proposed method was successfully applied to the assay of pseudoephedrine hydrochloride in commercial pharmaceutical formulations with good accuracy and precision and without interferences from common additives. Statistical comparison of the results with a well-established method showed excellent agreement and proved that there was no significant difference in the accuracy and precision. The stoichiometry of the reaction was determined and the reaction pathway was postulated. Copyright © 2010 John Wiley & Sons, Ltd.

In vitro inhibitory effects of palonosetron hydrochloride, bevacizumab and cyclophosphamide on purified paraoxonase-I (hPON1) from human serum.

PubMed

Türkeş, Cüneyt; Söyüt, Hakan; Beydemir, Şükrü

2016-03-01

In this study, we investigated the effects of the drugs, palonosetron hydrochloride, bevacizumab and cyclophosphamide, on human serum paraoxonase-I (hPON1) enzyme activity in in vitro conditions. The enzyme was purified ∼231-fold with 34.2% yield by using ammonium sulphate precipitation, DEAE-Sephadex A-50 ion-exchange chromatography and Sephadex G-200 gel-filtration chromatography from human serum. hPON1 exhibited a single protein band on the SDS polyacrylamide gel electrophoresis. The inhibition studies were performed on paraoxonase activity of palonosetron hydrochloride, bevacizumab and cyclophosphamide. Ki constants were found as 0.033±0.001, 0.054±0.003 mM and 3.419±0.518 mM, respectively. Compared to the inhibition rates of the drugs, palonosetron hydrochloride has the maximum inhibition rate. However, inhibition mechanisms of the drugs were determined as noncompetitive by Lineweaver-Burk curves. Copyright © 2016 Elsevier B.V. All rights reserved.

[Cevimeline hydrochloride hydrate (Saligren capsule 30 mg): a review of its pharmacological profiles and clinical potential in xerostomia].

PubMed

Shiozawa, Akira

2002-10-01

Cevimeline hydrochloride hydrate is a muscarinic receptor agonist with a chemical structure of a quinuclidine. Intraduodenal administration of cevimeline hydrochloride hydrate dose-dependently increased salivary secretion in normal mice and rats, two strains of autoimmune disease mice, and X-irradiated rats. The clinical efficacy of the cevimeline hydrochlide hydrate at 30 mg t.i.d. during 4 weeks has been demonstrated in double blind comparative study with placebo. In addition, its treatments in 52 weeks have increased salivary flow and improved subjective and objective symptoms of patients with xerostomia in Sjögren's syndrome.

Determination of noscapine, hexylresorcinol and anethole in cough lozenges by liquid chromatography.

PubMed

Lucangioli, S; Fernández Otero, G; Rodríguez, V; Carducci, C N

1996-06-01

A liquid chromatographic method was developed for the simultaneous separation and determination of noscapine hydrochloride, hexylresorcinol and anethole in cough lozenges. Analysis was performed on a phenyl column with phosphate buffer- acetonitrile as mobile phase and the separated components were detected at 282 mm. Recoveries obtained for the analytes were of 94.6% for noscapine hydrochloride, 99.1% for hexylresorcinol and 96.3% for anethole. The values of the relative standard deviation were 0.8% for noscapine hydrochloride, 1.5% for hexylresorcinol and 1.1% for anethole. The analytical method was validated and a system suitability test was accomplished for the chromatographic method.

Vibrational spectra of ketamine hydrochloride and 3, 4-methylenedioxymethamphetamine in terahertz range

NASA Astrophysics Data System (ADS)

Wang, Guangqin; Shen, Jingling; Jia, Yan

2007-07-01

The terahertz spectrum of ketamine hydrochloride at room temperature, in the range of 0.2-2.6THz, has been measured by terahertz time-domain spectroscopy (TDS). Full-geometry optimizations and frequency calculations using the density functional theory (DFT) are also applied to predict the absorption spectra of ketamine hydrochloride and 3, 4-methylenedioxymethamphetamine (MDMA). The results of the simulation show qualitative agreement with the experimental data especially for MDMA, and the observed spectra features are assigned based on the DFT calculation. The results suggest that use of the terahertz TDS technique can be an effective method for the detection and inspection of illicit drugs.

Feasibility of ion-pair/supercritical fluid extraction of an ionic compound--pseudoephedrine hydrochloride.

PubMed

Eckard, P R; Taylor, L T

1997-02-01

The supercritical fluid extraction (SFE) of an ionic compound, pseudoephedrine hydrochloride, from a spiked-sand surface was successfully demonstrated. The effect of carbon dioxide density (CO2), supercritical fluid composition (pure vs. methanol modified), and the addition of a commonly used reversed-phase liquid chromatographic ion-pairing reagent, 1-heptanesulfonic acid, sodium salt, on extraction efficiency was examined. The extraction recoveries of pseudoephedrine hydrochloride with the addition of the ion-pairing reagent from a spiked-sand surface were shown to be statistically greater than the extraction recoveries without the ion-pairing reagent with both pure and methanol-modified carbon dioxide.

Volumetric, rheological, and optical properties of hydroxylamine hydrochloride aqueous solutions containing NaCl, KCl, and NH4Cl at 30°C

NASA Astrophysics Data System (ADS)

Deosarkar, S. D.; Puyad, A. L.; Shaikh, U. B.; Solanke, S. S.

2014-04-01

Densities, viscosities, and refractive indices of aqueous solutions of hydroxylamine hydrochloride containing 0.05, 0.10, and 0.15 mol/dm3 NaCl, KCl, and NH4Cl were measured at different concentrations of hydroxylamine hydrochloride at 30°C. Viscosity coefficients A and B representing ion-ion and ion-solvent interactions were determined from Jones-Dole equation. Experimental properties and viscosity coefficients have been interpreted in terms of ion-ion and ion-solvent interactions. Ion-solvent interactions were found to be dominating over the ion-ion interactions in studied systems.

76 FR 64945 - Teva Pharmaceutical Industries Ltd. and Cephalon, Inc.; Analysis of Agreement Containing Consent...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-19

... Pharmaceutical, Inc. (``Par'') all of Teva's rights and assets relating to its generic transmucosal fentanyl citrate lozenges (``fentanyl citrate'') and generic extended release cyclobenzaprine hydrochloride..., by lessening competition in the U.S. markets for fentanyl citrate, cyclobenzaprine hydrochloride, and...

21 CFR 556.350 - Levamisole hydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.350 Levamisole hydrochloride. A tolerance of 0.1 part per...

21 CFR 556.350 - Levamisole hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.350 Levamisole hydrochloride. A tolerance of 0.1 part per...

21 CFR 556.350 - Levamisole hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.350 Levamisole hydrochloride. A tolerance of 0.1 part per...

21 CFR 556.410 - Metoserpate hydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.410 Metoserpate hydrochloride. A tolerance of 0.02 part per...

21 CFR 556.410 - Metoserpate hydrochloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.410 Metoserpate hydrochloride. A tolerance of 0.02 part per...

21 CFR 556.410 - Metoserpate hydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.410 Metoserpate hydrochloride. A tolerance of 0.02 part per...

21 CFR 556.350 - Levamisole hydrochloride.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.350 Levamisole hydrochloride. A tolerance of 0.1 part per...

21 CFR 556.350 - Levamisole hydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.350 Levamisole hydrochloride. A tolerance of 0.1 part per...

21 CFR 556.410 - Metoserpate hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.410 Metoserpate hydrochloride. A tolerance of 0.02 part per...

21 CFR 556.410 - Metoserpate hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.410 Metoserpate hydrochloride. A tolerance of 0.02 part per...

21 CFR 558.155 - Chlortetracycline, sulfathiazole, penicillin.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... (a) Approvals. Type A medicated articles: (1) 20 grams of chlortetracycline hydrochloride, 4.4 percent (20 grams) sulfathiazole, and procaine penicillin equivalent to 10 grams of penicillin per pound to No. 046573 in § 510.600(c) of this chapter. (2) 40 grams of chlortetracycline hydrochloride, 8.8...

21 CFR 558.155 - Chlortetracycline, sulfathiazole, penicillin.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... (a) Approvals. Type A medicated articles: (1) 20 grams of chlortetracycline hydrochloride, 4.4 percent (20 grams) sulfathiazole, and procaine penicillin equivalent to 10 grams of penicillin per pound to No. 046573 in § 510.600(c) of this chapter. (2) 40 grams of chlortetracycline hydrochloride, 8.8...

21 CFR 558.155 - Chlortetracycline, sulfathiazole, penicillin.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... (a) Approvals. Type A medicated articles: (1) 20 grams of chlortetracycline hydrochloride, 4.4 percent (20 grams) sulfathiazole, and procaine penicillin equivalent to 10 grams of penicillin per pound to No. 046573 in § 510.600(c) of this chapter. (2) 40 grams of chlortetracycline hydrochloride, 8.8...

21 CFR 558.155 - Chlortetracycline, sulfathiazole, penicillin.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... (a) Approvals. Type A medicated articles: (1) 20 grams of chlortetracycline hydrochloride, 4.4 percent (20 grams) sulfathiazole, and procaine penicillin equivalent to 10 grams of penicillin per pound to No. 046573 in § 510.600(c) of this chapter. (2) 40 grams of chlortetracycline hydrochloride, 8.8...

21 CFR 522.1462 - Naloxone hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Naloxone hydrochloride injection. 522.1462 Section 522.1462 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... antagonist in dogs. (2) It is administered by intravenous, intramuscular, or subcutaneous injection at an...

21 CFR 522.1462 - Naloxone hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Naloxone hydrochloride injection. 522.1462 Section 522.1462 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... antagonist in dogs. (2) It is administered by intravenous, intramuscular, or subcutaneous injection at an...

21 CFR 522.2615 - Tripelennamine hydrochloride injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Tripelennamine hydrochloride injection. 522.2615 Section 522.2615 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS...

75 FR 21162 - Certain Other Dosage Form New Animal Drugs; Detomidine

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-23

.... FDA-2010-N-0002] Certain Other Dosage Form New Animal Drugs; Detomidine AGENCY: Food and Drug... NADA provides for veterinary prescription use of detomidine hydrochloride oromucosal gel for sedation... prescription use of DORMOSEDAN GEL (detomidine hydrochloride) for sedation and restraint of horses. The...

21 CFR 522.234 - Butamisole hydrochloride.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Butamisole hydrochloride. 522.234 Section 522.234 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... a solution consisting of 70 percent propylene glycol, 4 percent benzyl alcohol and distilled water...

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Thiamine hydrochloride. 582.5875 Section 582.5875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary...

21 CFR 582.5875 - Thiamine hydrochloride.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Thiamine hydrochloride. 582.5875 Section 582.5875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary...

Study on the syhthesis process of tetracaine hydrochloride

NASA Astrophysics Data System (ADS)

Li, Wenli; Zhao, Jie; Cui, Yujie

2017-05-01

Tetrachloride hydrochloride is a local anesthetic with long-acting ester, and it is usually present in the form of a hydrochloride salt. Firsleb first synthesized the tetracaine by experiment in 1928, which is one of the recognized clinical potent anesthetics. This medicine has the advantages of stable physical and chemical properties, the rapid role and long maintenance. Tetracaine is also used for ophthalmic surface anesthesia as one of the main local anesthetic just like conduction block anesthesia, mucosal surface anesthesia and epidural anesthesia. So far, the research mainly engaged in its clinical application research, and the research strength is relatively small in the field of synthetic technology. The general cost of the existing production process is high, and the yield is low. In addition, the reaction time is long and the reaction conditions are harsh. In this paper, a new synthetic method was proposed for the synthesis of tetracaine hydrochloride. The reaction route has the advantages of few steps, high yield, short reaction time and mild reaction conditions. The cheap p-nitrobenzoic acid was selected as raw material. By esterification with ethanol and reaction with n-butyraldehyde (the reaction process includes nitro reduction, aldol condensation and hydrogenation reduction), the intermediate was transesterified with dimethylaminoethanol under basic conditions. Finally, the PH value was adjusted in the ethanol solvent. After experiencing 4 steps reaction, the crude tetracaine hydrochloride was obtained.

Gateways to Clinical Trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2002-09-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Adalimumab, aeroDose insulin inhaler, agomelatine, alendronic acid sodium salt, aliskiren fumarate, alteplase, amlodipine, aspirin, atazanavir; Bacillus Calmette-Guérin, basiliximab, BQ-788, bupropion hydrochloride; Cabergoline, caffeine citrate, carbamazepine, carvedilol, celecoxib, cyclosporine, clopidogrel hydrogensulfate, colestyramine; Dexamethasone, diclofenac sodium, digoxin, dipyridamole, docetaxel, dutasteride; Eletriptan, enfuvirtidie, eplerenone, ergotamine tartrate, esomeprazole magnesium, estramustine phosphate sodium; Finasteride, fluticasone propionate, fosinopril sodium; Ganciclovir, GBE-761-ONC, glatiramer acetate, gliclazide, granulocyte-CSF; Heparin sodium, human isophane insulin (pyr), Hydrochlorothiazide; Ibuprofen, inhaled insulin, interferon alfa, interferon beta-1a; Laminvudine, lansoprazole, lisinopril, lonafarnib, losartan potassium, lumiracoxib; MAb G250, meloxicam methotrexate, methylprednisolone aceponate, mitomycin, mycophenolate mofetil; Naproxen sodium, natalizumab, nelfinavir mesilate, nemifitide ditriflutate, nimesulide; Omalizumab, omapatrilat, omeprazole, oxybutynin chloride; Pantoprazole sodium, paracetamol, paroxetine, pentoxifylline, pergolide mesylate, permixon, phVEGF-A165, pramipexole hydrochloride, prasterone, prednisone, probucol, propiverine hydrochloride; Rabeprazole sodium, resiniferatoxin, risedronate sodium, risperidone, rofecoxib rosiglitazone maleate, ruboxistaurin mesilate hydrate; Selegiline transdermal system, sertraline, sildenafil citrate, streptokinase; Tadalafil, tamsulosin hydrochloride, technosphere/Insulin, tegaserod maleate, tenofovir disoproxil fumarate, testosterone heptanoate, testosterone undecanoate, tipifarnib, tolterodine tartrate, topiramate, troglitazone; Ursodeoxycholic acid; Valdecoxib, valsartan, vardenafil, venlafaxine hydrochloride, VX-745.

Quantitative HPLC Analysis of a Psychotherapeutic Medication: Simultaneous Determination of Amitriptyline Hydrochloride and Perphenazine

NASA Astrophysics Data System (ADS)

Ferguson, Glenda K.

1998-12-01

A quantitative high-performance liquid chromatography (HPLC) laboratory experiment which entails the isocratic separation and simultaneous determination of the two active components of a commercial antipsychotic tablet has been developed. The prescription formulation used in this experiment contains amitriptyline hydrochloride (a tricyclic antidepressant) and perphenazine (a tranquilizer). Our experiment makes use of a straightforward HPLC separation on a cyanopropyl-packed column with an acetonitrile:methanol:aqueous monopotassium phosphate mobile phase pumped at a flow rate of 2.0 mL/min. Analytes are detected by UV absorbance at 215 nm. These conditions yield highly symmetrical and well-resolved peaks in less than 5 min after the injection of a mixture. In the experiment, students are given amitriptyline hydrochloride-perphenazine tablets without the manufacturer's labeled composition claim and a stock solution mixture with known concentrations of amitriptyline hydrochloride and perphenazine. They prepare four standards and a pharmaceutical sample of unknown concentration, assay each solution in quadruplicate, and plot average peak areas of the concentrations of the known solutions in the construction of a standard curve. From the mathematical relationships that result, the average masses of amitriptyline hydrochloride and perphenazine in the prescription tablet are determined. Finally, the standard deviations of the mean masses are calculated. The entire laboratory procedure and statistical data analysis can be completed in a single 3-hour period.

EFFECT OF MAGNESIUM STEARATE CONCENTRATION ON DISSOLUTION PROPERTIES OF RANITIDINE HYDROCHLORIDE COATED TABLETS

PubMed Central

Uzunović, Alija; Vranić, Edina

2007-01-01

Most pharmaceutical formulations also include a certain amount of lubricant to improve their flowability and prevent their adhesion to the surfaces of processing equipment. Magnesium stearate is an additive that is most frequently used as a lubricant. Magnesium stearate is capable of forming films on other tablet excipients during prolonged mixing, leading to a prolonged drug liberation time, a decrease in hardness, and an increase in disintegration time. It is hydrophobic, and there are many reports in the literature concerning its adverse effect on dissolution rates. The objective of this study was to evaluate the effects of two different concentrations of magnesium stearate on dissolution properties of ranitidine hydrochloride coated tablet formulations labeled to contain 150 mg. The uniformity content was also checked. During the drug formulation development, several samples were designed for choice of the formulation. For this study, two formulations containing 0,77 and 1,1% of magnesium stearate added in the manufacture of cores were chosen. Fraction of ranitidine hydrochloride released in dissolution medium was calculated from calibration curves. The data were analyzed using pharmaco-peial test for similarity of dissolution profiles (f2 equation), previously proposed by Moore and Flanner. Application of f2 equation showed differences in time-course of ranitidine hydrochloride dissolution properties. The obtained values indicate differences in drug release from analyzed ranitidine hydrochloride formulations and could cause differences in therapeutic response. PMID:17848158

Up-regulation of Cav3.1 expression in SH-SY5Y cells induced by lidocaine hydrochloride.

PubMed

Gong, Qin; Wen, Xianjie; Li, Heng; He, Jian; Wang, Yunhua; Wu, Huiping; Wang, Hanbing; Wang, Xiaoping

2018-01-12

Neurotoxicity induced by the local anaesthetics has aroused concern. A previous study has shown that an overload of intracellular calcium was involved in the neurotoxic effect. Cav3.1 is one of the low-voltage-activated (LVA) calcium channels which play a key point to regulate the intracellular calcium ion level. This study aimed to investigate the changes of the Cav3.1 expression in the SH-SY5Y cells treated with lidocaine hydrochloride. The SH-SY5Y cells were treated with different concentrations of lidocaine hydrochloride(1 mM, 5 mM and 10 mM, namely L1 group, L5 group and L10 group) and different exposure times (1 h,12 h and 24 h), respectively. Cell viability, Cav3.1 protein and mRNA expression were detected. The results showed that cell viability decreased and Cav3.1 mRNA and protein expression increased with the concentration (from 1 mM to 10 mM) of the lidocaine hydrochloride and exposure time (from 1 h to 24 h) to the SH-SY5Y cell line increased. Those data showed that lidocaine hydrochloride induced SH-SY5Y cell toxicity and up-regulated Cav3.1mRNA and protein expression.

21 CFR 524.1484f - Neomycin sulfate, prednisolone acetate, tetracaine hydrochloride eardrops.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate, prednisolone acetate, tetracaine... DOSAGE FORM NEW ANIMAL DRUGS § 524.1484f Neomycin sulfate, prednisolone acetate, tetracaine hydrochloride eardrops. (a) Specifications. The product contains 5 milligrams of neomycin sulfate equivalent to 3.5...

21 CFR 524.1484b - Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride, and myristyl-gamma-picolinium...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate, isoflupredone acetate... Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride, and myristyl-gamma-picolinium chloride, topical powder. (a) Specifications. The product contains 5 milligrams of neomycin sulfate, equivalent to 3...

21 CFR 524.1484c - Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride ointment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate, isoflupredone acetate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1484c Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride ointment. (a) Specifications. The drug contains 5 milligrams of neomycin sulfate (equivalent to 3...

21 CFR 524.1484f - Neomycin sulfate, prednisolone acetate, tetracaine hydrochloride eardrops.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate, prednisolone acetate, tetracaine... DOSAGE FORM NEW ANIMAL DRUGS § 524.1484f Neomycin sulfate, prednisolone acetate, tetracaine hydrochloride eardrops. (a) Specifications. The product contains 5 milligrams of neomycin sulfate equivalent to 3.5...

21 CFR 524.1484b - Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride, and myristyl-gamma-picolinium...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Neomycin sulfate, isoflupredone acetate... Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride, and myristyl-gamma-picolinium chloride, topical powder. (a) Specifications. The product contains 5 milligrams of neomycin sulfate, equivalent to 3...

21 CFR 524.1484f - Neomycin sulfate, prednisolone acetate, tetracaine hydrochloride eardrops.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Neomycin sulfate, prednisolone acetate, tetracaine... DOSAGE FORM NEW ANIMAL DRUGS § 524.1484f Neomycin sulfate, prednisolone acetate, tetracaine hydrochloride eardrops. (a) Specifications. The product contains 5 milligrams of neomycin sulfate equivalent to 3.5...

21 CFR 524.1484b - Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride, and myristyl-gamma-picolinium...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate, isoflupredone acetate... Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride, and myristyl-gamma-picolinium chloride, topical powder. (a) Specifications. The product contains 5 milligrams of neomycin sulfate, equivalent to 3...

21 CFR 524.1484c - Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride ointment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate, isoflupredone acetate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1484c Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride ointment. (a) Specifications. The drug contains 5 milligrams of neomycin sulfate (equivalent to 3...

A Parent Guide To Understanding the Effects of Ritalin (Methylphenidate Hydrochloride).

ERIC Educational Resources Information Center

Villegas, Orlando; And Others

This guide provides information to help parents decide whether their child with attention deficit hyperactivity disorder (ADHD) should take methylphenidate hydrochloride (Ritalin). Information is provided in a question-and-answer format on various concerns, including: the meaning of ADHD, whether Ritalin is overprescribed, when this medication is…

Fate and transport of the ß-adrenergic agonist ractopamine hydrochloride in soil-water systems

USDA-ARS?s Scientific Manuscript database

The feed additive ractopamine hydrochloride was fortified at four concentrations into batch vials containing soils that differed in both biological activity and organic matter (OM). Sampling of the liquid layer for 14 d demonstrated that ractopamine rapidly dissipated from the liquid layer. Less t...

21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.863...

21 CFR 520.863 - Ethylisobutrazine hydrochloride tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ethylisobutrazine hydrochloride tablets. 520.863 Section 520.863 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.863...

21 CFR 184.1676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2011 CFR

2011-04-01

... hydrochloride that is prepared by chemical synthesis. (b) The ingredient meets the specifications of the Food... manufacturing practice conditions of use: (1) The ingredient is used as a nutrient supplement as defined in... exceed current good manufacturing practice: baked goods as defined in § 170.3(n)(1) of this chapter...

Zilpaterol hydrochloride affects cellular muscle metabolism and lipid components of ten different muscles in feedlot heifers

USDA-ARS?s Scientific Manuscript database

This study determined if zilpaterol hydrochloride (ZH) altered muscle metabolism and lipid components of ten muscles. Crossbred heifers were either supplemented with ZH (n = 9) or not (Control; n = 10). Muscle tissue was collected (adductor femoris, biceps femoris, gluteus medius, infraspinatus, lat...

76 FR 16533 - Certain Other Dosage Form New Animal Drugs; Detomidine; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-24

.... FDA-2010-N-0002] Certain Other Dosage Form New Animal Drugs; Detomidine; Correction AGENCY: Food and... paragraph describing limitations to the approved conditions of use for detomidine hydrochloride oromucosal... conditions of use for detomidine hydrochloride oromucosal gel in horses. This correction is being made to...

Contact dermatitis caused by intermediate products in the manufacture of clenbuterol, ranitidine base, and ranitidine hydrochloride.

PubMed

Romaguera, C; Grimalt, F; Vilaplana, J

1990-01-01

Clenbuterol, a beta antagonist, and ranitidine, a histamine-receptor antagonist, were associated with contact dermatitis in a chemist. The allergen in the former was an intermediate in the synthesis called beta. In the latter, intermediates and the finished base and hydrochloride were responsible.

Effect of Temperature on Electrical Conductivity of Guaiacol-Guanidine Hydrochloride-Formaldehyde Copolymer Resin

NASA Astrophysics Data System (ADS)

Kukade, S. D.; Bawankar, S. V.

2018-02-01

The purpose of the present paper is to report temperature dependence of electrical conductivity on Guaiacol-guanidine hydrochloride-formaldehyde copolymer resin. By using a microwave irradiation technique, various ratios of copolymer resin were synthesized from the reacting monomers, i.e., guaiacol, guanidine hydrochloride and formaldehyde. The characterization of the copolymer resins has been fulfilled by spectral methods viz. ultraviolet visible (UV visible), infrared and proton nuclear magnetic spectroscopy (1H-NMR). The solid state direct current electrical conductivity of synthesized copolymer resins has been measured as a function of temperature. The electrical conductivity values of all the copolymers have been found in the range of a semiconductor.

High-performance liquid chromatographic analysis of methadone hydrochloride oral solution.

PubMed

Beasley, T H; Ziegler, H W

1977-12-01

A direct and rapid high-performance liquid chromatographic assay for methadone hydrochloride in a flavored oral solution dosage form is described. A syrup sample, one part diluted with three parts of water, is introduced onto a column packed with octadecylsilane bonded on 10 micrometer porous silica gel (reversed phase). A formic acid-ammonium formate-buffered mobile phase is linear programmed with acetonitrile. The absorbance is monitored continuously at 280 or 254 nm, using a flow-through, UV, double-beam photometer. An aqueous methadone hydrochloride solution is used for external standardization. The relative standard deviation was not more than 1.0%. Drug recovery from a syrup base was better than 99.8%.

Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend.

PubMed

Kenawy, El-Refaie; Bowlin, Gary L; Mansfield, Kevin; Layman, John; Simpson, David G; Sanders, Elliot H; Wnek, Gary E

2002-05-17

Electrospun fiber mats are explored as drug delivery vehicles using tetracycline hydrochloride as a model drug. The mats were made either from poly(lactic acid) (PLA), poly(ethylene-co-vinyl acetate) (PEVA), or from a 50:50 blend of the two. The fibers were electrospun from chloroform solutions containing a small amount of methanol to solubilize the drug. The release of the tetracycline hydrochloride from these new drug delivery systems was followed by UV-VIS spectroscopy. Release profiles from the electrospun mats were compared to a commercially available drug delivery system, Actisite (Alza Corporation, Palo Alto, CA), as well as to cast films of the various formulations.

Cerebral perfusion imaging in Alzheimer's disease. Use of single photon emission computed tomography and iofetamine hydrochloride I 123

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, K.A.; Mueller, S.T.; Walshe, T.M.

1987-02-01

We used single photon emission computed tomography (SPECT) to study 15 patients with Alzheimer's disease and nine controls. Iofetamine hydrochloride I 123 uptake data were recorded from the entire brain using a rotating gamma camera. Activity ratios were measured for the frontal, posterior parietal, posterior, medial, and lateral cortical temporal regions and striate cortex and were normalized by the activity in the cerebellum. Abnormalities in iofetamine hydrochloride I 123 activity were similar to the abnormalities in glucose metabolism observed with positron emission tomography. Cortical tracer activity was globally depressed in patients with Alzheimer's disease, with the greatest reduction in themore » posterior parietal cortex.« less

21 CFR 522.2470 - Tiletamine hydrochloride and zolazepam hydrochloride for injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR... intramuscular dosage of 3 to 4.5 milligrams per pound of body weight for diagnostic purposes; 4.5 to 6 milligrams per pound of body weight for minor procedures of short duration such as repair of lacerations and...

21 CFR 522.2470 - Tiletamine hydrochloride and zolazepam hydrochloride for injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR... intramuscular dosage of 3 to 4.5 milligrams per pound of body weight for diagnostic purposes; 4.5 to 6 milligrams per pound of body weight for minor procedures of short duration such as repair of lacerations and...

21 CFR 522.723 - Diprenorphine hydrochloride injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diprenorphine hydrochloride injection. 522.723 Section 522.723 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... use in wild or exotic animals only. Do not use in domestic food-producing animals. Do not use 30 days...

21 CFR 520.1242b - Levamisole hydrochloride tablet or oblet (bolus).

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Levamisole hydrochloride tablet or oblet (bolus). 520.1242b Section 520.1242b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS...

21 CFR 520.1242 - Levamisole hydrochloride oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Levamisole hydrochloride oral dosage forms. 520.1242 Section 520.1242 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1242...

21 CFR 522.2470 - Tiletamine hydrochloride and zolazepam hydrochloride for injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... dogs for restraint and minor procedures of short duration (30 minutes) requiring mild to moderate analgesia. (2) Amount. Expressed as milligrams of the drug combination: (i) In healthy dogs: An initial intramuscular dosage of 3 to 4.5 milligrams per pound of body weight for diagnostic purposes; 4.5 to 6...

21 CFR 310.201 - Exemption for certain drugs limited by new-drug applications to prescription sale.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS New Drugs Exempted From..., Drug, and Cosmetic Act are not necessary for the protection of the public health with respect to the...-cyclohexylhexahydrobenzoic acid. β-diethylaminoethyl ester hydrochloride; diethylaminocarbethoxy-bicyclohexyl hydrochloride...

21 CFR 310.201 - Exemption for certain drugs limited by new-drug applications to prescription sale.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS New Drugs Exempted From..., Drug, and Cosmetic Act are not necessary for the protection of the public health with respect to the...-cyclohexylhexahydrobenzoic acid. β-diethylaminoethyl ester hydrochloride; diethylaminocarbethoxy-bicyclohexyl hydrochloride...

Effects of zilpaterol hydrochloride on methane production, total body oxygen consumption, and blood metabolites in finishing beef steers

USDA-ARS?s Scientific Manuscript database

An indirect calorimetry experiment was conducted to determine the effects of feeding zilpaterol hydrochloride (ZH) for 20 d on total body oxygen consumption, respiratory quotient, methane production, and blood metabolites in finishing beef steers. Sixteen Angus steers (initial BW = 555 ± 12.7 kg) w...

Performance of finishing beef steers in response to anabolic implant dose and zilpaterol hydrochloride

USDA-ARS?s Scientific Manuscript database

British × Continental steers (n = 168; 7 pens/treatment; initial BW = 362 kg) were used to evaluate the dose of trenbolone acetate (TBA) and estradiol-17ß (E2) and feeding of zilpaterol hydrochloride (ZH) on performance and carcass characteristics. A randomized complete block design was used with a ...

Performance of finishing beef steers in response to anabolic implant and zilpaterol hydrochloride supplementation

USDA-ARS?s Scientific Manuscript database

Our objectives were to evaluate the dose/payout pattern of trenbolone acetate (TBA) and estradiol-17b (E2) implants and feeding of zilpaterol hydrochloride (ZH) on performance and carcass characteristics of finishing beef steers. A randomized complete block design was used with a 3 × 2 factorial arr...

21 CFR 520.2345g - Tetracycline hydrochloride and sodium novobiocin tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... tablets. 520.2345g Section 520.2345g Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.2345g Tetracycline hydrochloride and sodium novobiocin tablets. (a) Specifications. Each tablet... antibiotic per pound of body weight (one single-strength tablet for each 6 pounds or one triple-strength...

77 FR 16036 - Determination That CITANEST (Prilocaine Hydrochloride) Injection, 1%, 2%, and 3%, and CITANEST...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-19

... marketing for reasons other than safety or effectiveness. ANDAs that refer to CITANEST (prilocaine HCl... Hydrochloride) Injection, 4%, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food... (prilocaine HCl) Injection, 4%, were not withdrawn from sale for reasons of safety or effectiveness. This...

Oxaliplatin, Fluorouracil, Erlotinib Hydrochloride, and Radiation Therapy Before Surgery and Erlotinib Hydrochloride After Surgery in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

ClinicalTrials.gov

2017-04-17

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Stomach; Squamous Cell Carcinoma of the Esophagus; Stage II Esophageal Cancer; Stage II Gastric Cancer; Stage III Esophageal Cancer; Stage III Gastric Cancer

21 CFR 184.1676 - Pyridoxine hydrochloride.

Code of Federal Regulations, 2014 CFR

2014-04-01

... exceed current good manufacturing practice: baked goods as defined in § 170.3(n)(1) of this chapter...)(31) of this chapter; plant protein products as defined in § 170.3(n)(33) of this chapter; and snack... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Pyridoxine hydrochloride. 184.1676 Section 184...

21 CFR 520.1263c - Lincomycin hydrochloride soluble powder.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Lincomycin hydrochloride soluble powder. 520.1263c Section 520.1263c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... for 7 consecutive days. Do not allow rabbits, hamsters, guinea pigs, horses, or ruminants access to...

21 CFR 520.1263c - Lincomycin hydrochloride soluble powder.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Lincomycin hydrochloride soluble powder. 520.1263c Section 520.1263c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... for 7 consecutive days. Do not allow rabbits, hamsters, guinea pigs, horses, or ruminants access to...

21 CFR 520.1263c - Lincomycin hydrochloride soluble powder.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Lincomycin hydrochloride soluble powder. 520.1263c Section 520.1263c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... for 7 consecutive days. Do not allow rabbits, hamsters, guinea pigs, horses, or ruminants access to...

Ambroxol Hydrochloride Combined with Fluconazole Reverses the Resistance of Candida albicans to Fluconazole.

PubMed

Li, Xiuyun; Zhao, Yuanhao; Huang, Xin; Yu, Cuixiang; Yang, Yilei; Sun, Shujuan

2017-01-01

In this study, we found that ambroxol hydrochloride (128 μg/mL) exhibits synergistic antifungal effects in combination with fluconazole (2 μg/mL) against resistant planktonic Candida albicans ( C. albicans ) cells. This combination also exhibited synergistic effects against resistant C. albicans biofilms in different stages (4, 8, and 12 h) according to the microdilution method. In vitro data were further confirmed by the success of this combination in treating Galleria mellonella infected by resistant C. albicans . With respect to the synergistic mechanism, our result revealed that ambroxol hydrochloride has an effect on the drug transporters of resistant C. albicans , increasing the uptake and decreasing the efflux of rhodamine 6G, a fluorescent alternate of fluconazole. This is the first study to investigate the in vitro and in vivo antifungal effects, as well as the possible synergistic mechanism of ambroxol hydrochloride in combination with fluconazole against resistant C. albicans . The results show the potential role for this drug combination as a therapeutic alternative to treat resistant C. albicans and provide insights into the development of antifungal targets and new antifungal agents.

Anaesthesia of nyala (Tragelaphus angasi) with a combination of thiafentanil (A3080), medetomidine and ketamine.

PubMed

Cooper, D V; Grobler, D; Bush, M; Jessup, D; Lance, W

2005-03-01

A combination of thiafentanil (A3080), medetomidine hydrochloride (MED) and ketamine hydrochloride (KET) was evaluated in 19 boma-habituated (12 female and 7 males) and 9 free-ranging nyala (7 male and 2 females) (Tragelaphus angasi) to develop a safe and reliable anaesthesia protocol. Wide dosages were used safely during this study with ranges for A3080 of 45 +/- 8 microg/kg with MED of 69 +/- 19 microg/kg and KET of 3.7 +/- 1.0 mg/kg (200 mg/ animal). The dosages developed on boma-habituated nyala proved to be equally effective in 9 adult free-ranging nyala (7 males and 2 females). The optimum dosage for nyala was a combination of A3080 (40-50 microg/kg), MED (60-80 microg/kg) plus 200 mg of KET/animal. The anaesthesia was characterised by a short induction, good muscle relaxation and mild hypoxaemia during monitoring the anaesthesia was rapidly and completely reversed by naltrexone hydrochloride (30 mg/mg of A3080) and atipamezole hydrochloride (5 mg/mg of MED) given intramuscularly. There was no mortality or morbidity associated with this protocol.

A new modification method of a Cetyl Trimethyl Ammonium Bromide/Nano-ZnO and Multi-walled Carbon Nanotubes Electrode for Determination of Anti Doping in Urine

NASA Astrophysics Data System (ADS)

Zhao, Zhiwei; Mu, Shuai; Zheng, Jie; Gu, Lingyan; Shen, Guijun; Shen, Yuan

2017-07-01

The preparation and application of Cetyl Trimethyl Ammonium Bromide/Nano-ZnO and Multi-walled Carbon Nanotubes (CTAB/ZnO-MWNTs) Modified Electrodes was studied, establishing a new electrochemical method for determination of carteolol hydrochloride in urine. After its pre-enrichment by adsorption and extraction on modified electrodes, electrochemical behaviors of carteolol hydrochloride on the modified electrodes were studied by CV and DPV. The response is linear at the range of 1×10-3 ∼ 2×10-1 g/L, with a detection limit of 2×10-4 g/L. Under appropriate conditions, the content of carteolol hydrochloride in urine can be determined directly by the method, which had strong anti-interference ability and the recovery is 96.5% - 110.5%. In addition, extraction and adsorption behaviors of the modified electrodes for carteolol hydrochloride were studied by chronocoulumetry, and the results showed that extraction during the enrichment process played a major role at low concentrations, and contribution of surface adsorption became greater with the increase of concentrations.

A study of selective spectrophotometric methods for simultaneous determination of Itopride hydrochloride and Rabeprazole sodium binary mixture: Resolving sever overlapping spectra

NASA Astrophysics Data System (ADS)

Mohamed, Heba M.

2015-02-01

Itopride hydrochloride (IT) and Rabeprazole sodium (RB) are co-formulated together for the treatment of gastro-esophageal reflux disease. Three simple, specific and accurate spectrophotometric methods were applied and validated for simultaneous determination of Itopride hydrochloride (IT) and Rabeprazole sodium (RB) namely; constant center (CC), ratio difference (RD) and mean centering of ratio spectra (MCR) spectrophotometric methods. Linear correlations were obtained in range of 10-110 μg/μL for Itopride hydrochloride and 4-44 μg/mL for Rabeprazole sodium. No preliminary separation steps were required prior the analysis of the two drugs using the proposed methods. Specificity was investigated by analyzing the synthetic mixtures containing the two cited drugs and their capsules dosage form. The obtained results were statistically compared with those obtained by the reported method, no significant difference was obtained with respect to accuracy and precision. The three methods were validated in accordance with ICH guidelines and can be used for quality control laboratories for IT and RB.

In vitro and in silico investigation of electrospun terbinafine hydrochloride-loaded buccal nanofibrous sheets.

PubMed

Szabó, Péter; Daróczi, Tünde Beáta; Tóth, Gergő; Zelkó, Romána

2016-11-30

Terbinafine hydrochloride-loaded nanofibrous buccal films were formulated with the aim to improve the solubility and dissolution behavior; thus, the local effectiveness of the antifungal agent. Poly(vinyl alcohol) and chitosan polymer composites were selected as delivery base in order to enhance the mucoadhesion of the fibrous films. The dissolution of terbinafine hydrochloride was carried out applying a stainless steel disc assembly and the terbinafine concentration was determined by HPLC-MS in selective ion monitoring mode. The prediction of the absorption behavior of the prepared fibrous samples in the human oral cavity was modeled using GastroPlus™ software. The result indicates that the fibrous films enabled fast and complete dissolution of the active agent. The drug absorption from the oral cavity could be minimized by the employment of the proper oral transit model. Because of the limited absorption of terbinafine hydrochloride from the oral mucosa the formulation can be beneficial in local administration in the case of hold and expectorate administration mode. Copyright © 2016 Elsevier B.V. All rights reserved.

A study of selective spectrophotometric methods for simultaneous determination of Itopride hydrochloride and Rabeprazole sodium binary mixture: Resolving sever overlapping spectra.

PubMed

Mohamed, Heba M

2015-02-05

Itopride hydrochloride (IT) and Rabeprazole sodium (RB) are co-formulated together for the treatment of gastro-esophageal reflux disease. Three simple, specific and accurate spectrophotometric methods were applied and validated for simultaneous determination of Itopride hydrochloride (IT) and Rabeprazole sodium (RB) namely; constant center (CC), ratio difference (RD) and mean centering of ratio spectra (MCR) spectrophotometric methods. Linear correlations were obtained in range of 10-110μg/μL for Itopride hydrochloride and 4-44μg/mL for Rabeprazole sodium. No preliminary separation steps were required prior the analysis of the two drugs using the proposed methods. Specificity was investigated by analyzing the synthetic mixtures containing the two cited drugs and their capsules dosage form. The obtained results were statistically compared with those obtained by the reported method, no significant difference was obtained with respect to accuracy and precision. The three methods were validated in accordance with ICH guidelines and can be used for quality control laboratories for IT and RB. Copyright © 2014 Elsevier B.V. All rights reserved.

[Simultaneous determination of ephedrine hydrochloride, D-pseudoephedrine and amygdalin in xiao'er pingchuan qutan granule by HPLC].

PubMed

Yang, De-Bin; Tong, Yan; Ma, Zhen-Shan; Wang, Lin; Dong, Mei-Hong; Li, Yan-Ling; Wang, Jin-Yu

2013-03-01

To establish an HPLC method for the determination of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin in Xiao'er Pingchuan Qutan granule. Pheny ether chromatographic column (4.6 mm x 250 mm, 5 microm) was adopted, with acetonitrile-0.1% phosphoric acid (containing 0.1% three ethylamine) (3:97) as the mobile phase. The UV detection wavelength was at 210 nm, with the flow rate of 1 mL x min(-1), and column temperature was at 35 degrees C. The linearity of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin ranged between 0.078 60-3.144 microg (r = 1.000 0), 0.103 4-2.068 microg (r = 0.999 7) and 0.430 5-3.157 microg (r = 0.999 8), respectively. Their average recoveries were 98.46% (RSD 1.1%), 103.0% (RSD 1.5%) and 97.15% (RSD 2.1%), respectively. The method is simple, stable and reliable that it can be used to determine the content of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin in Xiao'er Pingchuan Qutan granule.

Preparation and adsorption behavior of berberine hydrochloride imprinted polymers by using silica gel as sacrificed support material

NASA Astrophysics Data System (ADS)

Li, Hui; Li, Yuzhuo; Li, Zhiping; Peng, Xiyang; Li, Yanan; Li, Gui; Tan, Xianzhou; Chen, Gongxi

2012-03-01

Preparation of berberine hydrochloride (B-Cl) imprinted polymers (MIPs) based on surface imprinting technique with silica gel as sacrificial support material was performed successfully by using B-Cl as template, methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) as functional monomer and cross-linker, respectively. The prepared polymers were characterized by Fourier transmission infrared spectrometry (FTIR) and scanning electron microscopy (SEM). Adsorption behavior of the MIPs for the template and its structural analogues was investigated. Sites distribution on the surface of MIPs was explored by using different isotherm adsorption models and thermodynamic parameters for the adsorption of B-Cl on the MIPs determined. Sample application and reusability for the MIPs was also evaluated. Results indicated the strong adsorption and high selectivity of the MIPs for B-Cl. Saturated adsorption capacity reached 27.2 μmol g-1 and the selectivity coefficient of the MIPs for B-Cl relative to jatrorrhizine hydrochloride (J-Cl) and palmatine palmatus hydrochloride (P-Cl) are 3.70 and 6.03, respectively. In addition, the MIPs were shown with good reusability and selectively retention ability in sample application.

[Clinical observation of icotinib hydrochloride in first-line therapy for pulmonary adenocarcinoma].

PubMed

Yang, Xinjie; Zhang, Hui; Qin, Na; Li, Xi; Nong, Jingying; Lv, Jialin; Wu, Yuhua; Zhang, Quan; Zhang, Shucai

2013-07-01

It has been proven that icotinib hydrochloride, as a molecule targeted drug, can be safely and efficiently used to treat advanced non-small cell lung cancer (NSCLC) for second-line or third-line. This research was aimed to investigate the efficacy and toxicity of icotinib hydrochloride as the first-line therapy for pulmonary adenocarcinoma. Among the 56 patients, the tumor objective response rate (ORR) and disease control rate (DCR) was 46.4% (26/56) and 78.6% (46/56), respectively. Among the 20 patients with EGFR analyses, 18 patients were positive for a mutation, ORR was 66.7% (12/18), DCR was 94.4% (17/18) respectively. The ORR with no history of smoke. EGFR positive mutation and appearance of rash were significantly higher than those with smoker, wild type EGFR, no information about EGFR and no appearance of rash (P<0.05). The most common drug-related adverse events were mild skin rash (28.5%) and diarrhea (12%). Single agent treatment with icotinib hydrochloride is effective and tolerable in first-line therapy for pulmonary adenocarcinoma, especially with EGFR mutation.

Propranolol hydrochloride enhancement of tumor perfusion and uptake of gallium-67 in a mouse sarcoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bomber, P.; McCready, R.; Hammersley, P.

1986-02-01

The effect of propranolol hydrochloride on the blood perfusion of a mouse sarcoma and other tissues has been studied using /sup 86/Rb. The maximum increase in relative tumor perfusion (2x controls) occurred 15 min after an i.v. administration of 10 mg per kg propranolol hydrochloride. To study the effect of this drug on the uptake of /sup 67/Ga, it was injected at a concentration of 10 mg/kg 10 min before administering 3 microCi (110 kBq) (/sup 67/Ga)citrate. Tissue uptakes were measured 4 hr later. The tumor: blood ratio increased from 1.16 +/- 0.17 to 3.41 +/- 2.27 (s.d.) and tumor:more » liver ratio increased from 2.39 +/- 0.30 to 7.13 +/- 3.52 (s.d.). The results showed that propranolol hydrochloride can improve the relative tumor blood flow and radiopharmaceutical concentration in an animal model. It is hoped that this and other agents will yield similar results in the human situation.« less

The investigation of photo-induced chemiluminescence on Co2+-doped TiO2 nanoparticles and its analytical application.

PubMed

Li, Guixin; Nan, Hongyan; Zheng, Xingwang

2009-07-01

A novel space- and time-resolved photo-induced chemiluminescence (PICL) analytical method was developed based on the photocatalysis of the Co2+-doped TiO2 nanoparticles. The PICL reaction procedure under the photocatalysis of Co2+-doped TiO2 nanoparticles was investigated using cyclic voltammetry and potentiometry. Meanwhile, the effect of the electrical double layer outside the Co2+-doped TiO2 nanoparticles on the PICL was investigated by contrasting with the Co2+-doped TiO2-SiO2 core-shell nanoparticles. Significantly, the CL intensity increased apparently and the time of the CL was prolonged in the presence of procaterol hydrochloride because the mechanism of the enhanced PICL reaction may be modified. The route of the PICL was changed due to the participation of the procaterol hydrochloride enriched at the surface of the Co2+-doped TiO2-SiO2 in the PICL reaction, which prolonged the time of the CL reaction and resulted in the long-term PICL. The analytical characteristics of the proposed in-situ PICL method were investigated using the procaterol hydrochloride as the model analyte. The investigation results showed that this new PICL analytical method offered higher sensitivity to the analysis of the procaterol hydrochloride and the PICL intensity was linear with the concentration of the procaterol hydrochloride in the range from ca. 2.0 x 10(-10) to 1.0 x 10(-8) g mL(-1).

Stability of sotalol hydrochloride in extemporaneously prepared oral suspension formulations.

PubMed

Sidhom, Madiha B; Rivera, Nadya; Almoazen, Hassan; Taft, David R; Kirschenbaum, Harold L

2005-01-01

The physical, chemical, and microbial stabilities of extemporaneously compounded oral liquid formulations of sotalol hydrochloride were studied. Sotalol hydrochloride oral liquid suspensions (5mg/mL) were prepared from commercially available tablets (Betapace) in a 1:1 mixture of Ora-Plus: Ora-Sweet, a 1:1 mixture of Ora-Plus:Ora-Sweet SF, and a 1:2.4 mixture of simple syrup:methylcellulose vehicle. Six batches of each formulation were prepared; three were stored at refrigerated temperature (2 deg to 8 deg C) and three at room temperature (20 deg to 25 deg C). Samples were collected from each batch weekly for 6 weeks, and again at 12 weeks. Samples were analyzed by means of a high-performance liquid chromatographic method, and the concentrations obtained were compared to the theoretical time zero value. Samples were examined for pH, odor, color, and consistency changes. The suspensions also were evaluated for their microbial stability. Sotalol hydrochloride oral liquid suspensions (5mg/mL) were chemically stable for 12 weeks regardless of storage conditions (room temperature or refrigerated). Bacterial growth was not supported by any of the formulations. Suspensions stored at refrigerated temperature retained better physical quality (e.g., odor, color, and consistency) than suspensions stored at room temperature. Overall, this study demonstrates that oral formulations of sotalol hydrochloride can be readily prepared with commercially available vehicles. The method of preparation is relatively simple, the materials are relatively inexpensive, and the products have a shelf-life of at least 12 weeks.

Nanosized complexation assemblies housed inside reverse micelles churn out monocytic delivery cores for bendamustine hydrochloride.

PubMed

Singh, Yuvraj; Chandrashekhar, Anumandla; Meher, Jaya Gopal; Durga Rao Viswanadham, K K; Pawar, Vivek K; Raval, Kavit; Sharma, Komal; Singh, Pankaj K; Kumar, Animesh; Chourasia, Manish K

2017-04-01

We explore a plausible method of targeting bendamustine hydrochloride (BM) to circulatory monocytes by exploiting their intrinsic endocytic/phagocytic capability. We do so by complexation of sodium alginate and chitosan inside dioctyl sulfo succinate sodium (AOT) reverse micelles to form bendamustine hydrochloride loaded nanoparticles (CANPs). Dynamic light scattering, electrophoretic mobility and UV spectroscopy were used to detail intra-micellar complexation dynamics and to prove that drug was co-captured during interaction of carbohydrate polymers. A fluorescent conjugate of drug (RBM) was used to trace its intracellular fate after its loading into nanoparticles. CANPs were sized below 150nm, had 75% drug entrapment and negative zeta potential (-30mV). Confocal microscopy demonstrated that developed chitosan alginate nanoparticles had the unique capability to carry BM specifically to its site of action. Quantitative and mechanism based cell uptake studies revealed that monocytes had voracious capacity to internalize CANPs via simultaneous scavenger receptor based endocytic and phagocytic mechanism. Comparative in vitro pharmacokinetic studies revealed obtainment of significantly greater intracellular drug levels when cells were treated with CANPs. This caused reduction in IC 50 (22.5±2.1μg/mL), enhancement in G 2 M cell cycle arrest, greater intracellular reactive oxygen species generation, and increased apopotic potential of bendamustine hydrochloride in THP-1 cells. Selective monocytic targeting of bendamustine hydrochloride using carbohydrate constructs can prove advantageous in case of leukemic disorders displaying overabundance of such cells. Copyright © 2017 Elsevier B.V. All rights reserved.

In vitro and in vivo studies of pharmacokinetics and antitumor efficacy of D07001-F4, an oral gemcitabine formulation.

PubMed

Hao, Wei-Hua; Wang, Jong-Jing; Hsueh, Shu-Ping; Hsu, Pei-Jing; Chang, Li-Chien; Hsu, Chang-Shan; Hsu, Kuang-Yang

2013-02-01

The chemotherapy agent gemcitabine is currently administered intravenously because the drug has poor oral bioavailability. In order to assess the pharmacokinetics and antitumor activity of D07001-F4, a new self-microemulsifying oral drug delivery system preparation of gemcitabine, this study was performed to compare the effect of D07001-F4 with administered gemcitabine in vitro and in vivo. D07001-F4 pharmacokinetics was examined by evaluation of in vitro deamination of D07001-F4 and gemcitabine hydrochloride by recombinant human cytidine deaminase (rhCDA) and in vivo evaluation of D07001-F4 pharmacokinetics in mice. Antitumor activity was evaluated by comparing the effect of D07001-F4 and gemcitabine hydrochloride in inhibiting growth in nine cancer cell lines and by examining the effect of D07001-F4 and gemcitabine in two xenograft tumor models in mice. In vitro deamination of D07001-F4 by rhCDA was 3.3-fold slower than deamination of gemcitabine hydrochloride. Growth inhibition by D07001-F4 of 7 of the 8 cancer cell lines was increased compared with that seen with gemcitabine hydrochloride, and D07001-F4 inhibited the growth of pancreatic and colon cancer xenografts. In vivo pharmacokinetics showed the oral bioavailability of D07001-F4 to be 34%. D07001-F4 was effective against several cancer types, was metabolized more slowly than gemcitabine hydrochloride, and exhibited enhanced oral bioavailability.

Effect of formulation pH on transdermal penetration of antiemetics formulated in poloxamer lecithin organogel.

PubMed

Woodall, Rachel; Arnold, John J; McKay, Doug; Asbill, C Scott

2013-01-01

The purpose of this study was to assess the impact of altering formulation pH on the transdermal penetration of several commonly used antiemetic, weakly basic drugs incorporated into poloxamer lecithin organogel vehicle. Poloxamer lecithin organogel formulations containing promethazine hydrochloride (25 mg/mL), metoclopramide hydrochloride (10 mg/mL), and ondansetron hydrochloride (8 mg/mL) were examined for both drug release and transdermal penetration across porcine skin in modified Franz diffusion cells for a period of 24 hours. For the transdermal studies, each antiemetic drug was formulated at a pH above and below their acid dissociation constant (pKa) in an attempt to assure that the drug would be primarily in their respective ionized or non-ionized states. In addition, drug content in skin was assessed at the end of the 24-hour experiment. Drug content analysis was determined via high-performance liquid chromatography. As a percent of total drug release from the poloxamer lecithin organogel vehicle, promethazine hydrochloride demonstrated the most transdermal drug penetration after 24 hours (30.2% +/- 20.2%), followed by ondansetron hydrochloride (2.7% +/- 1.1%) and metoclopramide hydrochloride (1.8% +/- 1.6%). Subsequently, the pH of the Pluronic F-127 gel was adjusted in order to ensure that each antiemetic drug would be primarily in its unionized state. The transdermal permeation of each antiemetic drug primarily in its unionized state increased over that observed with the drug primarily in its ionized state after 24 hours (promethazine: 1.6-fold increase; metoclopramide: 1.3-fold increase; ondansetron: 1.8-fold increase). A similar trend was noted in the amount of each drug found in the skin after 24 hours (promethazine: 1.2-fold increase; metoclopramide: 2.4-fold increase; ondansetron: 3.0-fold increase). These results suggest that proper optimization of drug ionization state may be a useful strategy for compounding pharmacists to increase the efficacy of drugs intended for inclusion in transdermal formulations.

The analgesic efficacy of oxycodone hydrochloride versus fentanyl during outpatient artificial abortion operation: A randomized trial.

PubMed

Xie, Kangjie; Zhang, Wen; Fang, Wumei; Lian, Yanhong; Lin, Sufeng; Fang, Jun

2017-06-01

Problems like body movement, respiratory depression, and complained of pain are still common phenomenon in outpatient artificial abortion general anesthesia. Oxycodone hydrochloride is a semisynthetic opioid and has a good therapeutic effect on visceral pain. We hypothesize that oxycodone hydrochloride would be superior to fentanyl in outpatient artificial abortion surgery. In this clinical trial 149 American Society of Anesthesiologists (ASA) I or II female outpatients scheduled for elective artificial abortion surgeries under general anesthesia were randomly divided into 3 groups: oxycodone hydrochloride 0.06 mg/kg group (group A), oxycodone hydrochloride 0.08 mg/kg group (group B), and control group fentanyl 2 ug/kg (group C). The primary outcome was level body movement and respiratory depression during the surgery, the second outcome included the visual analogue scale (VAS) score 30 minutes after waking. A total of 120 participants completed the study, n = 40 in each group. There was no significant difference in patients' age, body mass index (BMI), preoperative heart rate, mean arterial blood pressure, consumption dose of propofol, intraoperative body movement type and times, and duration of surgery among the 3 groups (P > .05). Comparing the incidence of intraoperative respiratory depression and SPO2 < 90% among the 3 groups, group C's was significantly higher than those of groups A and B, and the difference was statistically significant (P < .05). Group A had no difference compared with group B. In VAS score 30minutes after waking, group C was the highest, followed by group A, with group B as the lowest. The difference among the 3 groups was statistically significant (P < .05), but a difference delta less than 1 on the VAS scale is not clinically significant. The analgesic effect of oxycodone hydrochloride at 0.06 mg/kg applied to painless artificial abortion surgery is not superior than that of fentanyl, but the incidence of intraoperative respiratory depression and hypoxemia is significantly lower than fentanyl.

Anesthetic efficacy and heart rate effects of the intraosseous injection of 1.5% etidocaine (1:200,000 epinephrine) after an inferior alveolar nerve block.

PubMed

Stabile, P; Reader, A; Gallatin, E; Beck, M; Weaver, J

2000-04-01

The purpose of this study was to determine the anesthetic efficacy and heart rate effects of an intraosseous (IO) injection of 1.5% etidocaine with 1:200,000 epinephrine after an inferior alveolar nerve block. In a repeated-measures designed study, 48 subjects randomly received 2 combinations of injections at 2 separate appointments. The combinations were an inferior alveolar nerve (IAN) block (with 3% mepivacaine) + IO injection with 1.8 mL of 1.5% etidocaine hydrochloride containing 1:200,000 epinephrine, and an IAN + mock IO injection. The first molar was blindly tested with a pulp tester at 2-minute cycles for 60 minutes after the injection. Anesthesia was considered successful when 2 consecutive 80 readings (no subject response) were obtained. Heart rate (pulse rate) was measured with a pulse oximeter. Lip numbness occurred in 100% of the subjects with both the techniques. For the first molar, anesthetic success for the IAN + mock IO and the IAN + IO etidocaine hydrochloride groups, respectively, were 81% and 100%. The differences were significant (P <.05) when the IAN + IO etidocaine hydrochloride technique was compared with the IAN + mock IO. A mean increase in heart rate of 32 beats/min occurred in 90% of the subjects with the IO injection of the etidocaine hydrochloride solution. In 89% of these subjects, the heart rate returned to within 5 beats of baseline values 4 minutes or less after solution deposition. The IO injection of 1.8 mL of 1.5% etidocaine hydrochloride with 1:200,000 epinephrine, when used to augment an inferior alveolar nerve block, significantly increased anesthetic success in the first molar. The majority of subjects receiving the IO injection of the etidocaine hydrochloride solution had a transient increase in heart rate.

Efficacy and influence factors of icotinib hydrochloride in treating advanced non-small cell lung cancer.

PubMed

Ma, X-H; Tian, T-D; Liu, H-M; Li, Q-J; Gao, Q-L; Li, L; Shi, B

2017-01-01

To evaluate the efficacy and safety of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and discuss the influence factors on efficacy. 120 treatment-experienced patients confirmed by pathology or cytology with stage III B-IV non-small cell lung cancer took icotinib hydrochloride and erlotinib orally until the occurrence of disease progression or serious adverse reactions. Then, the efficacy of icotinib hydrochloride and the related influence factors were analyzed. In icotinib hydrochloride group, the response rate and the disease control rate were 30.00% and 65.00%, and the median progression-free survival time was 179 days (95% CI: 103.21-254.78); in erlotinib group, the response rate and the disease control rate were 25.00% and 56.70%, and the median progression-free survival time was 121 days (95% CI: 95.05-146.94). Moreover, the objective response rate and the disease control rate of second-line therapy were both superior to the third-line and above therapy. The objective response rate of patients with complete response/partial response/stable disease after the first-line therapy was higher than that of patients without response after the first-line therapy (p<0.05), and the significant differences existed in the objective response rate and the disease control rate among mutant group, wild-type group, and unknown group (p<0.05). The response rate and the disease control rate of erythra group were higher than those of non-erythra group (p<0.05). It was showed in the univariate analysis that the progression-free survival was correlated with the smoking status and the epidermal growth factor receptor gene mutations. The icotinib hydrochloride is effective and safe in treating the treatment-experienced patients with advanced NSCLC, especially for patients with sensitive mutations.

Effects of shade and feeding zilpaterol hydrochloride to finishing steers on performance, carcass quality, mobility, and body temperature

USDA-ARS?s Scientific Manuscript database

Crossbred steers (n=480) were utilized to study the effects of shade and feeding zilpaterol hydrochloride (ZH) on performance, carcass quality, mobility, and body temperature (BT). A randomized block design with a 2×2 factorial arrangement of treatments was conducted with four replicates per treatme...

Determination of methadone hydrochloride in a maintenance dosage formulation.

PubMed

Hoffmann, T J; Thompson, R D

1975-07-01

A colorimetric method for direct quantitative assay of methadone hydrochloride in liquid oral dosage forms is presented. The procedure involves the formation of a dye complex with bromothymol blue buffer solution. The resultant complex is extracted with benzene and measured spectrophotometrically. Duplicate tests on the formulation showed 99.2% of the labeled amount of methadone.

Reaction of Orthoesters with Amine Hydrochlorides: An Introductory Organic Lab Experiment Combining Synthesis, Spectral Analysis, and Mechanistic Discovery

ERIC Educational Resources Information Center

Saba, Shahrokh; Ciaccio, James A.

2016-01-01

While orthoesters are often used by chemists as alkylating, acylating, and formylating agents, they are rarely encountered in introductory organic chemistry curricula. We describe a second-semester organic chemistry laboratory experiment in which students acetylate unknown amine hydrochloride salts with trimethyl orthoacetate (TMOA) in the absence…

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... milligrams of triflupromazine hydrochloride. (b) Sponsor. See No. 053501 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs and cats to relieve anxiety and to help control psychomotor... preanesthetic.1 (2) The drug is administered orally to dogs and cats at a dosage level of 1 to 2 milligrams per...

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... milligrams of triflupromazine hydrochloride. (b) Sponsor. See No. 053501 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs and cats to relieve anxiety and to help control psychomotor... preanesthetic.1 (2) The drug is administered orally to dogs and cats at a dosage level of 1 to 2 milligrams per...

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... milligrams of triflupromazine hydrochloride. (b) Sponsor. See No. 053501 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs and cats to relieve anxiety and to help control psychomotor... preanesthetic.1 (2) The drug is administered orally to dogs and cats at a dosage level of 1 to 2 milligrams per...

21 CFR 520.2582 - Triflupromazine hydrochloride tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... milligrams of triflupromazine hydrochloride. (b) Sponsor. See No. 053501 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs and cats to relieve anxiety and to help control psychomotor... preanesthetic.1 (2) The drug is administered orally to dogs and cats at a dosage level of 1 to 2 milligrams per...

Advanced Cancer Detection Center

DTIC Science & Technology

2009-01-01

Hydrochloride (Periactin®), With and Without a Nutritional Supplement, PediaSure, on Weight in Children with Cancer/Treatment Related Cachexia (HLMCC 0702...Prevention of Cancer/Treatment-Related Cachexia in Children Receiving Moderate to Highly Emetic Chemotherapy (HLMCC 0703) • Modafinil to Improve...hydrochloride (periactin) and megestrol acetate (megace) on weight in children with cancer/treatment-related cachexia . J Pediatr Hematol Oncol. 30(11

78 FR 23273 - Determination That the OXYCONTIN (Oxycodone Hydrochloride) Drug Products Covered by New Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

... Hydrochloride) Drug Products Covered by New Drug Application 20-553 Were Withdrawn From Sale for Reasons of... was often abused by manipulating the product to defeat its extended-release mechanism, causing the... example, by crushing the product to sprinkle it onto food or to administer it through a gastric tube. As...

2-(Decylthio)ethanamine hydrochloride: A new multifunctional biocide which enhances corrosion inhibition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walter, R.W.; Cooke, L.M.

1997-12-01

2-(Decylthio)ethanamine hydrochloride is a new multifunctional biocide that is registered for use in a variety of recirculating cooling water systems. This biocide has broad spectrum activity against bacteria, fungi and algae. It also has biofilm and corrosion inhibition properties. Data on these various activities will be presented for both laboratory and field evaluations.

78 FR 34108 - Determination That SUBOXONE (Buprenorphine Hydrochloride and Naloxone Hydrochloride) Sublingual...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... naloxone HCl) sublingual tablets, 2 mg/0.5 mg and 8 mg/2 mg, are the subject of NDA 20-733, held by Reckitt Benckiser Pharmaceuticals, Inc. (Reckitt), and initially approved on October 8, 2002. SUBOXONE is indicated...,'' http://www.rb.com/site/rkbr/templates/mediainvestorsgeneral2.aspx?pageid=1332&cc=GB , Reckitt Benckiser...

Electron paramagnetic resonance and FT-IR spectroscopic studies of glycine anhydride and betaine hydrochloride

NASA Astrophysics Data System (ADS)

Halim Başkan, M.; Kartal, Zeki; Aydın, Murat

2015-12-01

Gamma irradiated powders of glycine anhydride and betaine hydrochloride have been investigated at room temperature by electron paramagnetic resonance (EPR). In these compounds, the observed paramagnetic species were attributed to the R1 and R2 radicals, respectively. It was determined that the free electron interacted with environmental protons and 14N nucleus in both radicals. The EPR spectra of gamma irradiated powder samples remained unchanged at room temperature for two weeks after irradiation. Also, the Fourier Transform Infrared (FT-IR), FT-Raman and thermal analyses of both compounds were investigated. The functional groups in the molecular structures of glycine anhydride and betaine hydrochloride were identified by vibrational spectroscopies (FT-IR and FT-Raman).

Simultaneous determination of rosuvastatin and propranolol in their binary mixture by synchronous spectrofluorimetry

NASA Astrophysics Data System (ADS)

El-Abasawi, Nasr M.; Attia, Khalid A. M.; Abo-serie, Ahmad A. M.; Morshedy, Samir; Abdel-Fattah, Ashraf

2018-06-01

Simultaneous determination of rosuvastatin calcium and propranolol hydrochloride using the first derivative synchronous spectrofluorimetry was described. This method involves measuring the synchronous fluorescence of both drugs in ethanol using, Δ λ = 60 nm then the first derivative was recorded and the peak amplitudes were measured at 350 and 374 nm for rosuvastatin calcium and propranolol hydrochloride, respectively. Under the optimum conditions, the linear ranges of rosuvastatin calcium and propranolol hydrochloride were 0.2-2 μg/mL and 0.1-1 μg/mL, respectively. The method was used for quantitative analysis of the drugs in raw materials and pharmaceutical dosage form. The validity of the proposed method was assessed according to an international conference on harmonization (ICH) guidelines.

Study on fluorescence characteristics of duloxetine hydrochloride

NASA Astrophysics Data System (ADS)

Liu, Xiangping; Du, Yingxiang; Wu, Xiulan

2008-12-01

The fluorescence characteristics of duloxetine hydrochloride are studied in this paper. The fluorescence emission spectra of duloxetine demonstrate that intramolecular charge-transfer takes place between thiophene ring and napthalenyloxy group upon irradiation. The effects of excitation light, solvent system, variation of solution pH value, metal ions and vitamin C on the fluorescence spectra of duloxetine hydrochloride are elucidated, respectively. A spectrofluorometric method of quantitative determination of duloxetine in dosage form is reported for the first time, the linear range is 7.14 × 10 -8 mol/L to 1.43 × 10 -5 mol/L, the linear correlation coefficient r is equal to 0.9997, and the detection limit is 3.5 × 10 -8 mol/L. The accuracy and the precision are satisfactory.

Drug insight: If inhibitors as specific heart-rate-reducing agents.

PubMed

Borer, Jeffrey S

2004-12-01

Heart rate is determined primarily by spontaneously repeating net inward current carried by sodium ions and potassium ions through hyperpolarization-activated cyclic-nucleotide-gated channels. Within the heart, these channels are found most abundantly in sinoatrial cardiomyocytes. The channels open in response to membrane hyperpolarization, modulated by local cAMP concentrations. They permit activation of the I(f) current, which can be blocked specifically by molecules characterized by linked benzazepinone and benzocyclobutane rings, and which are devoid of effects on cardiac conduction, inotropy or peripheral vascular tone. The resulting heart-rate reduction has been effective in angina prevention in clinical trials involving 4,000 patients, using the prototype I(f) inhibitor, ivabradine. No serious adverse events have been attributed to the treatment; the most prominent side-effect is dose-related, always reversible and often transient visual symptoms that seldom result in voluntary drug discontinuation.

Practical Applications for Single Pill Combinations in the Cardiovascular Continuum

PubMed Central

Iellamo, Ferdinando; Werdan, Karl; Narkiewicz, Krzysztof; Rosano, Giuseppe

2017-01-01

Despite the availability of new drugs and devices, the treatment of cardiovascular disease remains suboptimal. Single-pill combination therapy offers a number of potential advantages. It can combine different classes of drugs to increase efficacy while mitigating the risks of treatment-related adverse events, reduce pill burden, lower medical cost, and improve patient adherence. Furthermore, in hypertension, single pill combinations include standard to lower doses of each drug than would be necessary to achieve goals with monotherapy, which may explain their better tolerability compared with higher dose monotherapy. Combination therapy is now established in the treatment of hypertension. In ischaemic heart disease, the concept of a preventative polypill has been studied, but its benefits have not been established conclusively. However, the combination of ivabradine and beta-blockers has proven efficacy in patients with stable angina pectoris. This combination has also demonstrated benefits in patients with chronic heart failure. PMID:28785474

Systemic therapy after first-line docetaxel in metastatic castration-resistant prostate cancer.

PubMed

Beardsley, Emma K; Chi, Kim N

2008-09-01

There is an urgent need for systemic treatment options for patients with castration-resistant prostate cancer who have progressed after receiving first-line docetaxel chemotherapy. The purpose of this article is to review recent developments in this area. Retreatment with docetaxel has been employed with evidence of activity in selected populations. Mitoxantrone, the previous first-line standard based on its palliative effect, has also been used with clinical responses observed; however, the symptom benefit in this setting has not been established. Several classes of cytotoxic agents have been tested including platinum agents (satraplatin), epothilones (ixabepilone and patupilone) and taxanes (XRP-6258). A number of targeted therapies have also been clinically evaluated including inhibitors of cytoprotective chaperones (OGX-011) and the vascular endothelial growth factor receptor (sorafenib, sunitinib, and cediranib). An area generating great interest has been the development of agents that target the androgen receptor axis more effectively (MDV3100 and abiraterone) with encouraging early phase trial results. There is no accepted standard systemic treatment for patients with castration resistant prostate cancer and progressive disease after docetaxel. Novel agents are in phase II and III clinical testing in this setting.

Long-term Stability of Vancomycin Hydrochloride in Glucose 5% Polyolefin Bags: The Brand Name Versus a Generic Product.

PubMed

Huvelle, Sophie; Godet, Marie; Hecq, Jean-Daniel; Gillet, Patricia; Jamart, Jacques; Galanti, Laurence M

2016-01-01

The objectives of this study were to determine if the preparation of vancomycin hydrochloride in advance of infusion could improve the quality of the drug, time management of drug delivery, cost savings of drug delivery, and to investigate the long-term stability of vancomycin hydrochloride (brand name Vancocin®) infusion in glucose 5% polyolefin bags versus the generic (Vancomycine®) at 5°C ± 3°C. Five bags of each infusion 1 g/100 mL vancomycin hydrochloride in 5% glucose (Vancocin ® and Vancomycine®) were stored up to 57 days at 5°C ± 3°C. A visual inspection and pH measurement were performed periodically during the storage, and the concentrations were measured by high-performance liquid chromatography-diode array detection. No color change or precipitation in the solution was observed throughout the study period. As recommended by the U.S. Food and Drug Administration, the lower confidence limit at 95% of the concentration for the solutions remained superior to 90% of the initial concentration up to 43 days for the brand vancomycin (Vancocin®) infusion (96% ± 2%) and up to 57 days for the generic (Vancomycine®) (95% ± 4%). The solutions prepared either from brand or generic vancomycin hydrochloride were chemically stable more than one month (43 days for the brand and 57 days for the generic solution) and could be prepared in advance in a centralized intravenous additive service facility. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Comparison of the antifungal efficacy of terbinafine hydrochloride and ciclopirox olamine containing formulations against the dermatophyte Trichophyton rubrum in an infected nail plate model.

PubMed

Täuber, Anja; Müller-Goymann, Christel C

2014-07-07

Onychomycosis is a fungal infection mostly induced by dermatophytes such as Trichophyton rubrum. Due to slow nail growth, the treatment takes 3-9 months depending on the nail size and infected area. Hence, high efficacy of the active ingredient without systemic side effects is of major interest. To test the efficacy of an antifungal formulation, an appropriate in vitro model reflecting the in vivo situation as close as possible is required. In this study, a variety of antifungal formulations, i.e., commercial ones (Ciclopoli and Lamisil cream), those used in compounding pharmacies (Pentravan) as well as poloxamer 407-based systems, have been evaluated in an infected nail plate model. The active pharmaceutical ingredients (APIs) were ciclopirox olamine and terbinafine hydrochloride. The poloxamer 407-based formulations consisted of poloxamer 407, double distilled water, propylene glycol, isopropyl alcohol, medium chain triglycerides and either 1% ciclopirox olamine or 1% terbinafine hydrochloride as API, respectively. Former studies have shown high permeation rates of terbinafine hydrochloride from similar poloxamer 407-based formulations with dimethyl isosorbide instead of propylene glycol. The present contribution shows superior inhibition of T. rubrum growth from poloxamer 407-based formulations in comparison to the commercial Lamisil cream. Moreover, poloxamer 407-based formulations were equally effective as the nail lacquer Ciclopoli even though the poloxamer formulations contained only 1% of the drug instead of 8% in the marketed lacquer. Poloxamer 407-based systems containing ciclopirox olamine proved to be about as effective as similar terbinafine hydrochloride systems.

Influence of lidocaine forms (salt vs. freebase) on properties of drug-eudragit® L100-55 extrudates prepared by reactive melt extrusion.

PubMed

Liu, Xu; Ma, Xiangyu; Kun, Eucharist; Guo, Xiaodi; Yu, Zhongxue; Zhang, Feng

2018-06-05

This study examines the preparation of sustained-release lidocaine polyelectrolyte complex using reactive melt extrusion. Eudragit L100-55 was selected as the ionic polymer. The influence of drug forms (freebase vs. hydrochloride salt) on lidocaine-Eudragit L100-55 interactions, physical stability, and dissolution properties of extrudates was investigated. It was confirmed by DSC, FT-IR and Raman spectroscopy that polyelectrolyte could only form via the acid-base reaction between Eudragit L100-55 and lidocaine freebase. Due to this ionic interaction, the lidocaine extrudate was physically more stable than the lidocaine hydrochloride extrudate during the storage under stressed condition. Drug release from lidocaine extrudate was a function of drug solubility, polymer solubility, drug-polymer interaction, and drug-induced microenvironment pH. At 30% drug loading, extrudate exhibited sustained release in aqueous media at pH 1.2 and 4.5. Due to the alkaline microenvironment pH induced by dissolved lidocaine, Eudragit L100-55 was solubilized and sustained-release was not achieved in water and aqueous media at pH 5.5. In comparison, lidocaine hydrochloride induced an acidic microenvironment. Drug release of lidocaine hydrochloride extrudate was similar at pH 1.2, 4.5, 5.5 and water with drug being released over 10 h. The release of lidocaine hydrochloride from the extrudates in these media was primarily controlled by microenvironment pH. It is concluded that different forms of lidocaine resulted in different drug-polymer interactions and distinctive physicochemical properties of extrudates. Copyright © 2018. Published by Elsevier B.V.

Efficacy and Safety of 5 Anesthetics in Adult Zebrafish (Danio rerio)

PubMed Central

Collymore, Chereen; Tolwani, Angela; Lieggi, Christine; Rasmussen, Skye

2014-01-01

Although the safety and efficacy of tricaine methanesulfonate (MS222) for anesthesia of fish are well established, other anesthetics used less commonly in fish have been less extensively evaluated. Therefore, we compared gradual cooling, lidocaine hydrochloride (300, 325, and 350 mg/L), metomidate hydrochloride (2, 4, 6, 8, and 10 mg/L), and isoflurane (0.5 mL/L) with MS222 (150 mg/L) for anesthesia of adult zebrafish. The efficacy and safety of each agent was evaluated by observing loss of equilibrium, slowing of opercular movement, response to tail-fin pinch, recovery time, and anesthesia-associated mortality rates. At 15 min after anesthetic recovery, we used a novel-tank test to evaluate whether anesthetic exposure influenced short-term anxiety-like behavior. Behavioral parameters measured included latency to enter and number of transitions to the upper half of the tank, number of erratic movements, and number of freezing bouts. Behavior after anesthesia was unaltered regardless of the anesthetic used. Efficacy and safety differed among the anesthetics evaluated. Gradual cooling was useful for short procedures requiring immobilization only, but all instrumentation and surfaces that come in contact with fish must be maintained at approximately 10 °C. MS222 and lidocaine hydrochloride at 325 mg/L were effective as anesthetic agents for surgical procedures in adult zebrafish, but isoflurane and high-dose lidocaine hydrochloride were unsuitable as sole anesthetic agents due to high (30%) mortality rates. Although MS222 remains the best choice for generating a surgical plane of anesthesia, metomidate hydrochloride and gradual cooling were useful for sedation and immobilization for nonpainful procedures. PMID:24602548

Evaluation of the effects of zilpateral hydrochloride supplementation on catecholamin response and other blood metabolites following a combined corticotropin releasing hormone and vasopressin challenge

USDA-ARS?s Scientific Manuscript database

The stress response of cattle supplemented with zilpaterol hydrochloride (ZH) has become a topic due to anecdotal claims of supplemented cattle responding poorly to stress. This study was designed to determine if differences exist in the catecholamine and blood metabolite response of ZH-supplemente...

The effects of zilpaterol hydrochloride and shade on blood metabolites of finishing beef steers

USDA-ARS?s Scientific Manuscript database

The effects of feeding zilpaterol hydrochloride (ZH) and shade were evaluated on blood metabolites and lung score in finishing beef steers. Cattle were fed 0 or 8.33 mg/kg ZH for 21 d with a 3- or 4-d withdrawal before harvest and were housed in open or shaded pens. Blood samples and lung scores w...

Effects of shade and feeding zilpaterol hydrochloride to finishing steers on performance, carcass quality, heat stress, mobility, and body temperature

USDA-ARS?s Scientific Manuscript database

Steers (n = 480) were used to study the effects of shade and feeding zilpaterol hydrochloride (ZH) on performance, carcass quality, heat stress, mobility, and body temperature (BT). A randomized block design with a 2 × 2 factorial arrangement of treatments was used with 4 replicates per treatment. F...

Pressure injection of methyl 2-benzimidazole carbamate hydrochloride solution as a control for Dutch elm disease

Treesearch

Garold F. Gregory; Thomas W. Jones

1973-01-01

A preliminary evaluation of the effectiveness of injecting methyl 2-benzimidazole carbamate hydrochloride solution into elms for prevention or cure of Dutch elm disease is reported. Symptom development was diminished or prevented in elms injected with fungicide before inoculation. Symptom development was arrested in all crown-inoculated diseased trees injected with the...

Effects feeding zilpaterol hydrochloride on growth performance, fillet yeild, and body composition of rainbow trout, nile, tilapia, and channel catfish

USDA-ARS?s Scientific Manuscript database

Zilpaterol hydrochloride (ZH) is a potent ß-adrenergic agonist (BAA) that has been used in feedlot cattle to increase average daily gain, feed efficiency, yield of trimmed cuts, and dress out percent. While positive effects of ZH have been observed in cattle, there have been no reports of this prod...

77 FR 9944 - Determination That REQUIP XL (Ropinerole Hydrochloride) Extended-Release Tablets, 3 Milligrams...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-21

... Parkinson's disease. REQUIP XL (ropinerole hydrochloride) extended-release tablets, 3 mg, are currently... amendments include what is now section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j... suspends approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines...

Supplementation of zilpaterol hydrochloride does not significantly alter the serum metabolic profile and metabolic enzyme profile of finishing heifers

USDA-ARS?s Scientific Manuscript database

Supplementation of zilpaterol hydrochloride (ZH; Zilmax®) to cattle has been implicated as having a negative impact on the well-being of cattle. However, there is no data to support or refute these claims. This study was designed to determine if differences exist in the serum metabolic profile and m...

DOD and VA Health Care: Medication Needs during Transitions May Not Be Managed for All Servicemembers

DTIC Science & Technology

2012-11-01

Asenapine Maleate < 0.1 Haloperidol  < 0.1 Chlorpromazine Hydrochloride  < 0.1 Chlordiazepoxide Hydrochloride  < 0.1 Lacosamide < 0.1...0.1 Haloperidol Lactate  < 0.1 Clobazam 0.0 Ethotoin 0.0 Felbamate  0.0 Mephobarbital 0.0 Meprobamate 0.0 Methsuximide 0.0 Molindone

Hyperaesthesia following genital herpes: a case report.

PubMed

Ooi, Catriona; Zawar, Vijay

2011-01-01

We report an adult female patient who presented with sacral radiculopathy as incapacitating dysthesias following primary genital herpes simplex, which later recurred. Despite use of systemic antiviral treatment, the painful syndrome in our patient persisted. The success in treatment was seen only after the addition of amitriptyline hydrochloride. The case is being presented here for its rare manifestation and novel use of amitriptyline hydrochloride.

Gemcitabine Hydrochloride and Cisplatin or High-Dose Methotrexate, Vinblastine, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Urothelial Cancer

ClinicalTrials.gov

2014-01-27

Anterior Urethral Cancer; Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Posterior Urethral Cancer; Recurrent Bladder Cancer; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Ureter Cancer; Urethral Cancer Associated With Invasive Bladder Cancer

The effect of zilpaterol hydrochloride supplementation on energy metabolism and nitrogen and carbon retention of steers fed at maintenance and fasting intake levels

USDA-ARS?s Scientific Manuscript database

An indirect calorimetry trial examined energy metabolism, apparent nutrient digestibility (appND), carbon retention (CR) and nitrogen retention (NR) of cattle supplemented with zilpaterol hydrochloride (Z). Beef steers (n=20; 463 ± 14 kg) blocked (n=5) by weight and source were individually fed and ...

Prebiotic Synthesis of Diaminopyrimidine and Thiocytosine

NASA Technical Reports Server (NTRS)

Robertson, Michael P.; Levy, Matthew; Miller, Stanley L.

1996-01-01

The reaction of guanidine hydrochloride with cyanoacetaldehyde gives high yields (40-85%) of 2,4-diaminopyrimidine under the concentrated conditions of a drying lagoon model of prebiotic synthesis, in contrast to the low yields previously obtained under more dilute conditions. The prebiotic source of cyanoacetaldehyde, cyanoacetylene, is produced from electric discharges under reducing conditions. The effect of pH and concentration of guanidine hydrochloride on the rate of synthesis and yield of diaminopyrimidine were investigated, as well as the hydrolysis of diaminopyrimidine to cytosine, isocytosine, and uracil. Thiourea also reacts with cyanoacetaldehyde to give 2-thiocytosine, but the pyrimidine yields are much lower than with guanidine hydrochloride or urea. Thiocytosine hydrolyzes to thiouracil and cytosine and then to uracil. This synthesis would have been a significant prebiotic source of 2-thiopyrimidines and 5-substituted derivatives of thiouracil, many of which occur in tRNA. The applicability of these results to the drying lagoon model of prebiotic synthesis was tested by dry-down experiments where dilute solutions of cyanoacetaldehyde, guanidine hydrochloride, and 0.5 M NaCl were evaporated over varying periods of time. The yields of diaminopyrimidine varied from 1 to 7%. These results show that drying lagoons and beaches may have been major sites of prebiotic syntheses.

The Influence of Chitosan Cross-linking on the Properties of Alginate Microparticles with Metformin Hydrochloride-In Vitro and In Vivo Evaluation.

PubMed

Szekalska, Marta; Sosnowska, Katarzyna; Zakrzeska, Agnieszka; Kasacka, Irena; Lewandowska, Alicja; Winnicka, Katarzyna

2017-01-22

Sodium alginate is a polymer with unique ability to gel with different cross-linking agents in result of ionic and electrostatic interactions. Chitosan cross-linked alginate provides improvement of swelling and mucoadhesive properties and might be used to design sustained release dosage forms. Therefore, the aim of this research was to develop and evaluate possibility of preparing chitosan cross-linked alginate microparticles containing metformin hydrochloride by the spray-drying method. In addition, influence of cross-linking agent on the properties of microparticles was evaluated. Formulation of microparticles prepared by the spray drying of 2% alginate solution cross-linked by 0.1% chitosan was characterized by good mucoadhesive properties, high drug loading and prolonged metformin hydrochloride release. It was shown that designed microparticles reduced rat glucose blood level, delayed absorption of metformin hydrochloride and provided stable plasma drug concentration. Additionally, histopathological studies of pancreas, liver and kidneys indicated that all prepared microparticles improved degenerative changes in organs of diabetic rats. Moreover, no toxicity effect and no changes in rats behavior after oral administration of chitosan cross-linked alginate microparticles were noted.

In vitro antifungal activity of antipsychotic drugs and their combinations with conventional antifungals against Scedosporium and Pseudallescheria isolates.

PubMed

Homa, Mónika; Galgóczy, László; Tóth, Eszter; Tóth, Liliána; Papp, Tamás; Chandrasekaran, Muthusamy; Kadaikunnan, Shine; Alharbi, Naiyf S; Vágvölgyi, Csaba

2015-11-01

In the present study, in vitro antifungal activities of five antipsychotic drugs (i.e., chlorpromazine hydrochloride, CPZ; trifluoperazine hydrochloride, TPZ; amantadine hydrochloride; R-(-)-deprenyl hydrochloride, and valproic acid sodium salt) and five conventional antifungal drugs (i.e., amphotericin B, AMB; caspofungin, CSP; itraconazole; terbinafine, TRB and voriconazole, VRC) were investigated in broth microdilution tests against four clinical and five environmental Scedosporium and Pseudallescheria isolates. When used alone, phenothiazines CPZ and TPZ exerted remarkable antifungal effects. Thus, their in vitro combinations with AMB, CSP, VRC, and TRB were also examined against the clinical isolates. In combination with antifungal agents, CPZ was able to act synergistically with AMB and TRB in cases of one and two isolates, respectively. In all other cases, indifferent interactions were revealed. Antagonism was not observed between the tested agents. These combinations may establish a more effective and less toxic therapy after further in vitro and in vivo studies for Scedosporium and Pseudallescheria infections. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Suppression of glutamate-induced excitotoxicity by 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride in rat glial cultures.

PubMed

Kim, Eun-A; Hahn, Hoh-Gyu; Kim, Key-Sun; Kim, Tae Ue; Choi, Soo Young; Cho, Sung-Woo

2010-07-01

We have screened new drugs with a view to developing effective drugs against glutamate-induced excitotoxicity. In the present work, we show effects of a new drug, 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride against glutamate-induced excitotoxicity in primary rat glial cultures. Pretreatment of glial cells with 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride for 2 h significantly protected glial cells against glutamate-induced excitotoxicity in a time- and dose-dependent manner with an optimum concentration of 100 microM. The drug significantly reduced production of proinflammatory cytokines, tumor necrosis factor-alpha, and interlukin-1beta in glutamate-induced excitotoxicity. The drug also prevented glutamate-induced intracellular Ca2+ influx and reduced the subsequent overproduction of nitric oxide and reactive oxygen species. Furthermore, the drug preserved the mitochondrial potential and inhibited the overproduction of cytochrome c. In addition, the drug effectively attenuated the protein level changes of beta-catenin and glycogen synthase kinase-3beta. These results suggest that 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride effectively protected primary cultures of rat glial cells against glutamate-induced excitotoxicity.

Duration of Action of Bupivacaine Hydrochloride Used for Palatal Sensory Nerve Block in Infant Pigs

PubMed Central

Holman, Shaina Devi; Gierbolini-Norat, Estela M.; Lukasik, Stacey L.; Campbell-Malone, Regina; Ding, Peng; German, Rebecca Z.

2015-01-01

Summary Bupivacaine hydrochloride is frequently used in veterinary dental procedures to reduce the amount of general anesthesia needed and to reduce post-procedural pain. The aim of this study was to develop a novel method to test local anesthetic duration in mammals. Six infant pigs were placed under deep/surgical anesthesia with 3 % isoflurane and oxygen while 0.5 ml of 0.5 % bupivacaine hydrochloride was injected to block the two greater palatine and the nasopalatine nerves. They were then maintained under light anesthesia with 0.5–1.0 % isoflurane. Beginning 15-minutes after the injection, 7 sites in the oral cavity were stimulated using a pointed dental waxing instrument, including 3 sites on the hard palate. The response, or lack of response, to the stimulus was recorded on video and in written record. The bupivacaine hydrochloride injections lasted 1 to 3-hours before the animals responded to the sensory stimulation with a reflexive movement. This study provides evidence that bupivacaine used to anesthetize the hard palate has a relatively short and variable duration of action far below what is expected based on its pharmacokinetic properties. PMID:25185333

Invariom based electron density studies on the C/Si analogues haloperidol/sila-haloperidol and venlafaxine/sila-venlafaxine.

PubMed

Luger, Peter; Dittrich, Birger; Tacke, Reinhold

2015-09-14

The subjects of this study are the structures and electron densities of the carbon/silicon analogues haloperidol/sila-haloperidol (1a/1b) and venlafaxine/sila-venlafaxine (2a/2b). The parent carbon compounds 1a (an antipsychotic agent) and 2a (an antidepressant) are both in clinical use. For haloperidol/sila-haloperidol, three published structures were studied in more detail: the structures of haloperidol hydrochloride (1a·HCl), haloperidol hydropicrate (1a·HPic) and sila-haloperidol hydrochloride (1b·HCl). For venlafaxine/sila-venlafaxine, the published structures of venlafaxine (2a), venlafaxine hydrochloride (2a·HCl; as orthorhombic (2a·HCl-ortho) and monoclinic polymorph (2a·HCl-mono)) and sila-venlafaxine hydrochloride (2b·HCl) were investigated. Based on these structures, the molecular electron densities were reconstructed by using the invariom formalism. They were further analysed in terms of Bader's quantum theory of atoms in molecules, electrostatic potentials mapped onto electron density isosurfaces and Hirshfeld surfaces. These studies were performed with a special emphasis on the comparison of the corresponding carbon/silicon analogues.

Nifekalant hydrochloride suppresses severe electrical storm in patients with malignant ventricular tachyarrhythmias.

PubMed

Washizuka, Takashi; Chinushi, Masaomi; Watanabe, Hiroshi; Hosaka, Yukio; Komura, Satoru; Sugiura, Hirotaka; Hirono, Takashi; Furushima, Hiroshi; Tanabe, Yasutaka; Aizawa, Yoshifusa

2005-12-01

Some patients with an implantable cardioverter-defibrillator (ICD) suffer from burst of inappropriate multiple discharges (severe electrical storm), and because the current therapeutic options are limited, the effect of nifekalant hydrochloride, a new class III drug, on severe electrical storm was investigated in the present study. Ninety-one consecutive patients treated with ICD were included in the study (M 70; mean age 58 years; left ventricular ejection fraction 45+/-15%). Severe electrical storm was defined as more than 10 ICD discharges within 1 h. During a mean follow-up period of 30+/-13 months, 41/91 (45%) patients had appropriate ICD therapy for arrhythmias and severe electrical storm occurred in 11 of them (12%) at 20+/-18 months after ICD implantation. The mean number of ICD discharges/h during severe electrical storm was 18+/-12. In 4 of 10 patients, severe electrical storm was successfully suppressed by a combination of deep sedation and beta-blocking agent; 6 other patients were refractory to this treatment, but severe electrical storm was successfully suppressed by intravenous administration of nifekalant hydrochloride with no adverse effects. Nifekalant hydrochloride is an effective and safe treatment for severe electrical storm.

Taspine is the cicatrizant principle in Sangre de Grado extracted from Croton lechleri.

PubMed

Vaisberg, A J; Milla, M; Planas, M C; Cordova, J L; de Agusti, E R; Ferreyra, R; Mustiga, M C; Carlin, L; Hammond, G B

1989-04-01

Sangre de Grado extract used by Peruvian natives as a cicatrizant agent, was collected from trees of the species Croton lechleri growing in the Peruvian jungle. The Sangre de Grado was found to contain one alkaloid identified as taspine and which was shown to be the active cicatrizant principle by an in vivo test in mice. This alkaloid exhibited a dose-related cicatrizant effect and an ED50 of 0.375 mg/kg. Experiments with taspine hydrochloride in order to study its mechanism of action in cell culture systems showed that the alkaloid was non-toxic to human foreskin fibroblasts at concentrations below 150 ng/ml and that it had no effect on cell proliferation. On the other hand, taspine hydrochloride was found to increase the migration of human foreskin fibroblasts. This effect on the migration of fibroblasts is probably the mechanism by which Sangre de Grado and taspine hydrochloride accelerate the wound healing process. Using the two-stage mouse skin carcinogenesis system, we have been able to show that neither Sangre de Grado nor taspine hydrochloride had carcinogenic or tumour promoter activity after 17 months of treatment.

The Th1/Th2/Th17/Treg paradigm induced by stachydrine hydrochloride reduces uterine bleeding in RU486-induced abortion mice.

PubMed

Li, Xia; Wang, Bin; Li, Yuzhu; Wang, Li; Zhao, Xiangzhong; Zhou, Xianbin; Guo, Yuqi; Jiang, Guosheng; Yao, Chengfang

2013-01-09

The Th1/Th2/Th17/Treg paradigm plays an important role in achieving maternal-fetal immunotolerance and participates in RU486-induced abortion. Excessive uterine bleeding is the most common side effect of RU486-induced abortion; however, its etiopathogenesis has not been fully understood. Therefore, elucidating the correlation between the Th1/Th2/Th17/Treg paradigm and the volume of uterine bleeding may offer novel therapeutic target for reducing uterine bleeding in RU486-induced abortion. Leonurus sibiricus has been used in clinics to reduce postpartum hemorrhage with low toxicity and high efficiency; however, the effective constituents and therapeutic mechanism have not been described. Stachydrine hydrochloride is the main constituent of L. sibiricus, therefore L. sibiricus is regarded as a candidate for reducing uterine bleeding in RU486-induced abortion mice by regulating the Th1/Th2/Th17/Treg paradigm. The purpose of this study was to determine the Th1/Th2/Th17/Treg paradigm in uterine bleeding of RU486-induced abortion mice and to elucidate the immunopharmacologic effects of stachydrine hydrochloride on inducing the Th1/Th2/Th17/Treg paradigm in reducing the uterine bleeding volume in RU486-induced abortion mice. To investigate the Th1/Th2/Th17/Treg paradigm in uterine bleeding during RU486-induced abortion mice, pregnant BALB/c mice were treated with high- and low-dose RU486 (1.5mg/kg and 0.9 mg/kg, respectively), and the serum progesterone (P(4)) protein level, uterine bleeding volume, and proportions of Th1/Th2/Th17/Treg cells in mice at the maternal-fetal interface were detected by ELISA assay, alkaline hematin photometric assay, and flow cytometry, respectively. To determine the regulatory effect of stachydrine hydrochloride on the Th1/Th2/Th17/Treg paradigm in vitro, splenocytes of non-pregnant mice were separated and treated with P(4,) RU486, and/or stachydrine hydrochloride (10(-5)M, 10(-4)M, and 10(-3)M, respectively). The proportions of Th1/Th2/Th17/Treg cells were analyzed using flow cytometry. To evaluate the effect of stachydrine hydrochloride in reducing uterine bleeding via regulation of the Th1/Th2/Th17/Treg paradigm, pregnant mice were treated with RU486 (1.5mg/kg) and/or stachydrine hydrochloride (2.5mg/kg, 5mg/kg, and 10mg/kg). The serum P(4) level, uterine bleeding volume, and proportions of Th1/Th2/Th17/Treg cells at the mice maternal-fetal interface were detected. Moreover, the protein levels of cytokines (IL-12 and IL-6) and the cytokine soluble receptors were analyzed by ELISA assay, and the mRNA expression of transcription factors (T-bet, GATA-3, RORγt, and Foxp3) were detected by RT-PCR assay. Th1- and Th17-biased immunity was observed in RU486-induced abortion mice. The volume of uterine bleeding during RU486-induced abortion was negatively related to the proportions of Th1 and Th17 cells, as well as the ratios of Th1:Th2 cells and Th17:Treg cells, and positively related to the proportions of Th2 and Treg cells. Stachydrine hydrochloride promoted the protein expression of IL-12 and IL-6, as well as the mRNA expression of T-bet and RORγt, while inhibiting the mRNA expression of GATA-3 and Foxp3. Therefore, the Th1/Th2/Th17/Treg paradigm in RU486-induced abortion mice shifted to Th1 and Th17 after stachydrine hydrochloride administration. The volume of uterine bleeding during RU486-induced abortion was reduced significantly after stachydrine hydrochloride administration. The Th1/Th2/Th17/Treg paradigm is closely related to the volume of uterine bleeding in RU486-induced abortion mice. The Th1/Th2/Th17/Treg paradigm induced by stachydrine hydrochloride contributed to the reduction in uterine bleeding in RU486-induced abortion mice. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Study of the recrystallization in coated pellets - effect of coating on API crystallinity.

PubMed

Nikowitz, Krisztina; Pintye-Hódi, Klára; Regdon, Géza

2013-02-14

Coated diltiazem hydrochloride-containing pellets were prepared using the solution layering technique. Unusual thermal behavior was detected with differential scanning calorimetry (DSC) and its source was determined using thermogravimetry (TG), X-ray powder diffraction (XRPD) and hot-stage microscopy. The coated pellets contained diltiazem hydrochloride both in crystalline and amorphous form. Crystallization occurs on heat treatment causing an exothermic peak on the DSC curves that only appears in pellets containing both diltiazem hydrochloride and the coating. Results indicate that the amorphous fraction is situated in the coating layer. The migration of drugs into the coating layer can cause changes in its degree of crystallinity. Polymeric coating materials should therefore be investigated as possible crystallization inhibitors. Copyright © 2012 Elsevier B.V. All rights reserved.

Performance of Machine Learning Algorithms for Qualitative and Quantitative Prediction Drug Blockade of hERG1 channel.

PubMed

Wacker, Soren; Noskov, Sergei Yu

2018-05-01

Drug-induced abnormal heart rhythm known as Torsades de Pointes (TdP) is a potential lethal ventricular tachycardia found in many patients. Even newly released anti-arrhythmic drugs, like ivabradine with HCN channel as a primary target, block the hERG potassium current in overlapping concentration interval. Promiscuous drug block to hERG channel may potentially lead to perturbation of the action potential duration (APD) and TdP, especially when with combined with polypharmacy and/or electrolyte disturbances. The example of novel anti-arrhythmic ivabradine illustrates clinically important and ongoing deficit in drug design and warrants for better screening methods. There is an urgent need to develop new approaches for rapid and accurate assessment of how drugs with complex interactions and multiple subcellular targets can predispose or protect from drug-induced TdP. One of the unexpected outcomes of compulsory hERG screening implemented in USA and European Union resulted in large datasets of IC 50 values for various molecules entering the market. The abundant data allows now to construct predictive machine-learning (ML) models. Novel ML algorithms and techniques promise better accuracy in determining IC 50 values of hERG blockade that is comparable or surpassing that of the earlier QSAR or molecular modeling technique. To test the performance of modern ML techniques, we have developed a computational platform integrating various workflows for quantitative structure activity relationship (QSAR) models using data from the ChEMBL database. To establish predictive powers of ML-based algorithms we computed IC 50 values for large dataset of molecules and compared it to automated patch clamp system for a large dataset of hERG blocking and non-blocking drugs, an industry gold standard in studies of cardiotoxicity. The optimal protocol with high sensitivity and predictive power is based on the novel eXtreme gradient boosting (XGBoost) algorithm. The ML-platform with XGBoost displays excellent performance with a coefficient of determination of up to R 2 ~0.8 for pIC 50 values in evaluation datasets, surpassing other metrics and approaches available in literature. Ultimately, the ML-based platform developed in our work is a scalable framework with automation potential to interact with other developing technologies in cardiotoxicity field, including high-throughput electrophysiology measurements delivering large datasets of profiled drugs, rapid synthesis and drug development via progress in synthetic biology.

An updated computational model of rabbit sinoatrial action potential to investigate the mechanisms of heart rate modulation

PubMed Central

Severi, Stefano; Fantini, Matteo; Charawi, Lara A; DiFrancesco, Dario

2012-01-01

The cellular basis of cardiac pacemaking is still debated. Reliable computational models of the sinoatrial node (SAN) action potential (AP) may help gain a deeper understanding of the phenomenon. Recently, novel models incorporating detailed Ca2+-handling dynamics have been proposed, but they fail to reproduce a number of experimental data, and more specifically effects of ‘funny’ (If) current modifications. We therefore developed a SAN AP model, based on available experimental data, in an attempt to reproduce physiological and pharmacological heart rate modulation. Cell compartmentalization and intracellular Ca2+-handling mechanisms were formulated as in the Maltsev–Lakatta model, focusing on Ca2+-cycling processes. Membrane current equations were revised on the basis of published experimental data. Modifications of the formulation of currents/pumps/exchangers to simulate If blockers, autonomic modulators and Ca2+-dependent mechanisms (ivabradine, caesium, acetylcholine, isoprenaline, BAPTA) were derived from experimental data. The model generates AP waveforms typical of rabbit SAN cells, whose parameters fall within the experimental ranges: 352 ms cycle length, 80 mV AP amplitude, −58 mV maximum diastolic potential (MDP), 108 ms APD50, and 7.1 V s−1 maximum upstroke velocity. Rate modulation by If-blocking drugs agrees with experimental findings: 20% and 22% caesium-induced (5 mm) and ivabradine-induced (3 μm) rate reductions, respectively, due to changes in diastolic depolarization (DD) slope, with no changes in either MDP or take-off potential (TOP). The model consistently reproduces the effects of autonomic modulation: 20% rate decrease with 10 nm acetylcholine and 28% increase with 1 μm isoprenaline, again entirely due to increase in the DD slope, with no changes in either MDP or TOP. Model testing of BAPTA effects showed slowing of rate, −26%, without cessation of beating. Our up-to-date model describes satisfactorily experimental data concerning autonomic stimulation, funny-channel blockade and inhibition of the Ca2+-related system by BAPTA, making it a useful tool for further investigation. Simulation results suggest that a detailed description of the intracellular Ca2+ fluxes is fully compatible with the observation that If is a major component of pacemaking and rate modulation. PMID:22711956

Effect of feeding ractopamine hydrochloride on growth performance and responses to handling and transport in heavy-weight pigs

USDA-ARS?s Scientific Manuscript database

The impact of feeding ractopamine hydrochloride (RAC) on growth performance and responses to handling and transport in heavy BW pigs was evaluated in a study carried out as a split-plot design with a 3 × 3 factorial arrangement of treatments: 1) RAC level (0 vs. 5 vs. 7.5 mg/kg); 2) Handling Intensi...

Antiemetic Therapy With or Without Olanzapine in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients With Cancer Receiving Highly Emetogenic Chemotherapy | Division of Cancer Prevention

Cancer.gov

This randomized phase III trial studies antiemetic therapy with olanzapine to see how well they work compared to antiemetic therapy alone in preventing chemotherapy-induced nausea and vomiting in patients with cancer receiving highly emetogenic (causes vomiting) chemotherapy. Antiemetic drugs, such as palonosetron hydrochloride, ondansetron, and granisetron hydrochloride, may

Development of a drug assay using surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Angel, S. M.; Roe, Jeffrey N.; Andresen, Brian D.; Myrick, Michael L.; Milanovich, Fred P.

1990-07-01

Surface-enhanced Raman spectroscopy has been used to detect low levels of several chemical compounds, including the drugs of abuse -cocaine hydrochloride and methamphetamme hydrochloride. Raman spectra of these substances have also been taken over optical fibers using red-wavelength excitation. These measurements demonstrate the feasibility of the remote determination of various target chemicals using diode laser excitation and diode array detection.

Evaluation of the effects of zilpateral hydrochloride supplementation on catecholamine response and other blood metabolites following a combined corticotropin releasing hormone and vasopressin challenge

USDA-ARS?s Scientific Manuscript database

Supplementation of zilpaterol hydrochloride (ZH; Zilmax®) to cattle has been implicated as having a negative impact on the well-being of cattle. However, there is no data to support or refute these claims. This study was designed to determine if differences exist in the serum metabolic profile and m...

Supplementation of zilpaterol hydrochloride to crossbred Angus heifers does not increase stress responsiveness or homeostatic metabolic parameters after a combined corticoptropin releasing hormone and vasopressin challenge

USDA-ARS?s Scientific Manuscript database

Anecdotal claims suggest that feeding zilpaterol hydrochloride (ZH) alters the stress response in cattle; however, there is no scientific data to support or refute these claims. This study was designed to determine if differences exist in the stress response of ZH-supplemented cattle when exposed to...

Hyperaesthesia Following Genital Herpes: A Case Report

PubMed Central

Ooi, Catriona; Zawar, Vijay

2011-01-01

We report an adult female patient who presented with sacral radiculopathy as incapacitating dysthesias following primary genital herpes simplex, which later recurred. Despite use of systemic antiviral treatment, the painful syndrome in our patient persisted. The success in treatment was seen only after the addition of amitriptyline hydrochloride. The case is being presented here for its rare manifestation and novel use of amitriptyline hydrochloride. PMID:21747842

The effect of PI3K inhibitor LY294002 and gemcitabine hydrochloride combined with ionizing radiation on the formation of vasculogenic mimicry of Panc-1 cells in vitro and in vivo.

PubMed

Bai, R; Ding, T; Zhao, J; Liu, S; Zhang, L; Lan, X; Yu, Y; Yin, L

2016-01-01

This research's purpose was to explore the existence of vasculogenic mimicry (VM) in both 3-D matrices of Panc-1 cells in vitro and orthotopic Panc-1 xenografts in vivo and to test the hypothesis that PI3K inhibitor LY294002 and gemcitabine hydrochloride would offer clear treatment benefit when integrated into ionizing radiation (IR) therapeutic regimens for treatment of pancreatic cancer. We explored the existence of VM in both 3-D matrices of Panc-1 cells and orthotopic Panc-1 xenografts. We subsequently investigated the activation of the PI3K/MMPs/Ln-5γ2 signaling pathway in response to IR. LY294002 and gemcitabine hydrochloride were then evaluated for their radiosensitizing effect solely and in combination. We found that VM existed in both 3-D matrices of Panc-1 cells in vitro and orthotopic Panc-1 xenografts in vivo. The expressions of p-Akt and MMP- 2 were found to increase in response to IR. LY294002 and gemcitabine hydrochloride combined with IR better inhibited cell migration, VM formation and MMP-2 mRNA expression of Panc-1 cells in vitro, and we also proved that the novel therapeutic regimen better inhibited tumor growth, tumor metastasis and VM formation of orthotopic Panc-1 xenografts by suppressing the PI3K/MMPs/Ln-5γ2 signaling pathway in vivo. Our present study is among the first to prove the VM formation in orthotopic Panc-1 xenografts. Furthermore, our current study is also among the first to provide preliminary evidence for the use of the novel therapeutic regimen LY294002 and gemcitabine hydrochloride combined with IR for treatment of pancreatic cancer.

Pyridostigmine treatment trial in neurogenic orthostatic hypotension.

PubMed

Singer, Wolfgang; Sandroni, Paola; Opfer-Gehrking, Tonette L; Suarez, Guillermo A; Klein, Caroline M; Hines, Stacy; O'Brien, Peter C; Slezak, Jeffrey; Low, Phillip A

2006-04-01

Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension (OH) but it significantly worsens supine hypertension. By enhancing ganglionic transmission, pyridostigmine bromide can potentially ameliorate OH without worsening supine hypertension. To evaluate the efficacy of a single 60-mg dose of pyridostigmine bromide, alone or in combination with a subthreshold (2.5 mg) or suprathreshold (5 mg) dose of midodrine hydrochloride, compared with placebo. We report a double-blind, randomized, 4-way cross-over study of pyridostigmine in the treatment of neurogenic OH. A total of 58 patients with neurogenic OH were enrolled. After 1 day of baseline measurements, patients were given 4 treatments (3 active treatments [60 mg of pyridostigmine bromide; 60 mg of pyridostigmine bromide and 2.5 mg of midodrine hydrochloride; 60 mg of pyridostigmine bromide and 5 mg of midodrine hydrochloride] and a placebo) in random order on successive days. Blood pressure (BP) and heart rate were measured, both supine and standing, immediately before treatment and hourly for 6 hours after the treatment was given. No significant differences were seen in the supine BP, either systolic (P = .36) or diastolic (P = .85). In contrast, the primary end point of the fall in standing diastolic BP was significantly reduced (P = .02) with treatment. Pairwise comparison showed significant reduction by pyridostigmine alone (BP fall of 27.6 mm Hg vs 34.0 mm Hg with placebo; P = .04) and pyridostigmine and 5 mg of midodrine hydrochloride (BP fall of 27.2 mm Hg vs 34.0 mm Hg with placebo; P = .002). Standing BP improvement significantly regressed with improvement in OH symptoms. Pyridostigmine significantly improves standing BP in patients with OH without worsening supine hypertension. The greatest effect is on diastolic BP, suggesting that the improvement is due to increased total peripheral resistance.

Simultaneous determination of eperisone hydrochloride and paracetamol in mouse plasma by high performance liquid chromatography-photodiode array detector.

PubMed

Locatelli, Marcello; Cifelli, Roberta; Di Legge, Cristina; Barbacane, Renato Carmine; Costa, Nicola; Fresta, Massimo; Celia, Christian; Capolupo, Carlo; Di Marzio, Luisa

2015-04-03

This paper reports the validation of a quantitative high performance liquid chromatography-photodiode array (HPLC-PDA) method for the simultaneous analysis, in mouse plasma, of eperisone hydrochloride and paracetamol by protein precipitation using zinc sulphate-methanol-acetonitrile. The analytes were resolved on a Gemini C18 column (4.6 mm × 250 mm; 5 μm particle size) using a gradient elution mode with a run time of 15 min, comprising re-equilibration, at 60°C (± 1°C). The method was validated over the concentration range from 0.5 to 25 μg/mL for eperisone hydrochloride and paracetamol, in mouse plasma. Ciprofloxacin was used as Internal Standard. Results from assay validations show that the method is selective, sensitive and robust. The limit of quantification of the method was 0.5 μg/mL for eperisone hydrochloride and paracetamol, and matrix-matched standard curves showed a good linearity, up to 25 μg/mL with correlation coefficients (r(2))≥ 0.9891. In the entire analytical range the intra and inter-day precision (RSD%) values were ≤ 1.15% and ≤ 1.46% for eperisone hydrochloride, and ≤ 0.35% and ≤ 1.65% for paracetamol. For both analytes the intra and inter-day trueness (bias%) values ranged, respectively, from -5.33% to 4.00% and from -11.4% to -4.00%. The method was successfully tested in pharmacokinetic studies after oral administration in mouse. Furthermore, the application of this method results in a significant reduction in terms of animal number, dosage, and improvement in speed, rate of analysis, and quality of pharmacokinetic parameters related to serial blood sampling. Copyright © 2015 Elsevier B.V. All rights reserved.

Microparticulate drug delivery system containing tramadol hydrochloride for pain treatment.

PubMed

Ciurba, Adriana; Todoran, Nicoleta; Vari, C E; Lazăr, Luminita; Al Hussein, Stela; Hancu, G

2014-01-01

The current trend of replacing conventional pharmaceutical forms is justified because most substances administered in this form give fluctuations of therapeutic concentrations and often outside the therapeutic range. In addition, these formulations offer a reduction in the dose or the number of administrations, thus increasing patient compliance. In the experiment, we developed an appropriate technology for the preparation of gelatin microspheres containing tramadol hydrochloride by emulsification/cross-linking method. The formulated microspheres were characterized by product yield, size distribution, encapsulation efficiency and in vitro release of tramadol hydrochloride. Data obtained from in vitro release studies were fitted to various mathematical models to elucidate the transport mechanisms. The kinetic models used were zero-order, first-order, Higuchi Korsmeyer-Peppas and Hopfenberg. Spherical microspheres were obtained, with free-flowing properties. The entrapment efficiency of tramadol hydrochloride in microparticles was 79.91% and product yield -94.92%. As the microsphere size was increased, the entrapment efficiency increased. This was 67.56, 70.03, 79.91% for formulations MT80-250, MT8-500 and, MT250-500. High entrapment efficiency was observed for MT250-500 formulation. The gelatin microspheres had particle sizes ranging from 80 to 500 microm. The drug was released for a period of 12 hours with a maximum release of 96.02%. Of the three proposed formulations, MT250-500 presented desirable properties and optimal characteristics for the therapy of pain. Release of tramadol hydrochloridi was best fitted to Korsmeyer-Peppas equation because the Akaike Information Criterion had the lowest values for this kinetic model. These results suggest the opportunity to influence the therapeutic characteristics of gelatin microspheres to obtain a suitable drug delivery system for the oral administration of tramadol hydrochloride.

Studies on optimizing in vitro transdermal permeation of ondansetron hydrochloride using nerodilol, carvone, and limonene as penetration enhancers.

PubMed

Krishnaiah, Yellela S R; Raju, Vengaladasu; Shiva Kumar, Mantri; Rama, Bukka; Raghumurthy, Vanambattina; Ramana Murthy, Kolapalli V

2008-01-01

The present investigation was carried out to formulate a terpene-based hydroxypropyl cellulose (HPC) gel drug reservoir system for its optimal transdermal permeation of ondansetron hydrochloride. The HPC gel formulations containing ondansetron hydrochloride (3% w/w) and selected concentrations of either nerodilol (0% w/w, 1% w/w, 2% w/w, 3% w/w, and 4% w/w), carvone (0% w/w, 2% w/w, 4% w/w, 8% w/w, and 10% w/w), or limonene (0% w/w, 2% w/w, 3% w/w, and 4% w/w) were prepared and subjected to in vitro permeation of the drug across rat epidermis. All the 3 terpene enhancers increased the transdermal permeation of ondansetron hydrochloride. The optimal transdermal permeation was observed with 3% w/w of nerodilol (175.3 +/- 3.1 microg/cm(2.)h), 8% w/w of carvone (87.4 +/- 1.6 microg/cm(2.)h), or 3% w/w of limonene (181.9 +/- 0.9 microg/cm(2.)h). The enhancement ratio (ER) in drug permeability with 3% w/w nerodilol, 8% w/w carvone, and 3% w/w limonene were 21.6, 10.8, and 22.5, respectively, when compared with that obtained without a terpene enhancer (control). However, there was 1.04-, 2.09-, and 2.17-fold increase in the optimal drug flux obtained with carvone, nerodilol, and limonene, respectively, when compared with the desired drug flux (84 microg/cm(2.)h). It was concluded that the HPC gel drug reservoir systems containing either 3% w/w nerodilol or 3% w/w limonene act as optimal formulations for use in the design of membrane-controlled transdermal therapeutic system (TTS) of ondansetron hydrochloride.

Treatment with thiamine hydrochloride and astaxanthine for the prevention of yolk-sac mortality in Baltic salmon fry (M74 syndrome).

PubMed

Koski, P; Pakarinen, M; Nakari, T; Soivio, A; Hartikainen, K

1999-09-14

Two practical methods are reported for treating feral Baltic salmon with thiamine hydrochloride against M74 syndrome (abnormally high yolk-sac fry mortality of the Baltic salmon). Both bathing of the yolk-sac fry in thiamine hydrochloride (1000 mg l-1, 1 h) and a single intraperitoneal injection given to the female brood fish (100 mg kg-1 fish) during the summer 3 mo before stripping were shown to elevate the whole body total thiamine concentration in the fry. Both treatments were also shown to be effective in preventing mortality due to M74 syndrome. The effect of bathing the yolk-sac fry was shown to be dose-dependent. The results support the view that there is a causal relationship between the thiamine status of the yolk-sac fry and M74 mortality. An intraperitoneal injection of astaxanthine suspension administered to the female brood fish (11 mg kg-1 fish) in the summer 3 mo before stripping elevated the astaxanthine concentration in the eggs but did not affect mortality due to M74 syndrome. An interaction between astaxanthine and thiamine may occur in the developing embryo or yolk-sac fry, however. No association could be demonstrated between the various thiamine hydrochloride treatment practices and hepatic cytochrome P450 dependent 7-ethoxyresorufin-O-deethylase (EROD) activity in the yolk-sac fry. An injection of thiamine hydrochloride into the peritoneal cavity of wild Baltic salmon females could be used to raise thiamine concentrations in their offspring in the rivers. The effect on smolt production in Finnish Baltic salmon rivers needs to be investigated further, however.

Effects of MK-467 hydrochloride and hyoscine butylbromide on cardiorespiratory and gastrointestinal changes induced by detomidine hydrochloride in horses.

PubMed

Tapio, Heidi A; Raekallio, Marja R; Mykkänen, Anna; Mama, Khursheed; Mendez-Angulo, Jóse L; Hautajärvi, Heidi; Vainio, Outi M

2018-04-01

OBJECTIVE To compare the effects of MK-467 and hyoscine butylbromide on detomidine hydrochloride-induced cardiorespiratory and gastrointestinal changes in horses. ANIMALS 6 healthy adult horses. PROCEDURES Horses received detomidine hydrochloride (20 μg/kg, IV), followed 10 minutes later by MK-467 hydrochloride (150 μg/kg; DET-MK), hyoscine butylbromide (0.2 mg/kg; DET-HYO), or saline (0.9% NaCl) solution (DET-S), IV, in a Latin square design. Heart rate, respiratory rate, rectal temperature, arterial and venous blood pressures, and cardiac output were measured; blood gases and arterial plasma drug concentrations were analyzed; selected cardiopulmonary variables were calculated; and sedation and gastrointestinal borborygmi were scored at predetermined time points. Differences among treatments or within treatments over time were analyzed statistically. RESULTS With DET-MK, detomidine-induced hypertension and bradycardia were reversed shortly after MK-467 injection. Marked tachycardia and hypertension were observed with DET-HYO. Mean heart rate and mean arterial blood pressure differed significantly among all treatments from 15 to 35 and 15 to 40 minutes after detomidine injection, respectively. Cardiac output was greater with DET-MK and DET-HYO than with DET-S 15 minutes after detomidine injection, but left ventricular workload was significantly higher with DET-HYO. Borborygmus score, reduced with all treatments, was most rapidly restored with DET-MK. Sedation scores and pharmacokinetic parameters of detomidine did not differ between DET-S and DET-MK. CONCLUSIONS AND CLINICAL RELEVANCE MK-467 reversed or attenuated cardiovascular and gastrointestinal effects of detomidine without notable adverse effects or alterations in detomidine-induced sedation in horses. Further research is needed to determine whether these advantages are found in clinical patients and to assess whether the drug influences analgesic effects of detomidine.

Quantification of bupivacaine hydrochloride and isoflupredone acetate residues in porcine muscle, beef, milk, egg, shrimp, flatfish, and eel using a simplified extraction method coupled with liquid chromatography-triple quadrupole tandem mass spectrometry.

PubMed

Cho, Sang-Hyun; Park, Jin-A; Zheng, Weijia; Abd El-Aty, A M; Kim, Seong-Kwan; Choi, Jeong-Min; Yi, Hee; Cho, Soo-Min; Afifi, Nehal A; Shim, Jae-Han; Chang, Byung-Joon; Kim, Jin-Suk; Shin, Ho-Chul

2017-10-15

In this study, a simple analytical approach has been developed and validated for the determination of bupivacaine hydrochloride and isoflupredone acetate residues in porcine muscle, beef, milk, egg, shrimp, flatfish, and eel using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A 0.1% solution of acetic acid in acetonitrile combined with n-hexane was used for deproteinization and defatting of all tested matrices and the target drugs were well separated on a Waters Xbridge™ C18 analytical column using a mobile phase consisting of 0.1% acetic acid (A) and 0.1% solution of acetic acid in methanol (B). The linearity estimated from six-point matrix-matched calibrations was good, with coefficients of determination ≥0.9873. The limits of quantification (LOQs) for bupivacaine hydrochloride and isoflupredone acetate were 1 and 2ngg -1 , respectively. Recovery percentages in the ranges of 72.51-112.39% (bupivacaine hydrochloride) and 72.58-114.56% (isoflupredone acetate) were obtained from three different fortification concentrations with relative standard deviations (RSDs) of <15.14%. All samples for the experimental work and method application were collected from the local markets in Seoul, Republic of Korea, and none of them tested positive for the target drugs. In conclusion, a simple method using a 0.1% solution of acetic acid in acetonitrile and n-hexane followed by LC-MS/MS could effectively extract bupivacaine hydrochloride and isoflupredone acetate from porcine muscle, beef, milk, egg, shrimp, flatfish, and eel samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Morphological changes in the sciatic nerve, skeletal muscle, heart and brain of rabbits receiving continuous sciatic nerve block with 0.2% ropivacaine.

PubMed

Zhou, Yangning; He, Miao; Zou, Tianxiao; Yu, Bin

2015-01-01

To investigate the morphological changes in various tissues of rabbits receiving sciatic nerve block with 0.2% ropivacaine for 48 h. Twenty healthy were randomly assigned to normal saline group (N group) and ropivacaine group (R group). The right sciatic nerve was exposed, and a nerve-blocking trocar cannula embedded. Animals received an injection of 0.5% ropivacaine hydrochloride at a dose of 0.75 ml/kg. Rabbit was then connected to an infusion pump containing 50 ml of normal saline in N group, or to a infusion pump containing 0.2% ropivacaine hydrochloride in R group at 0.25 ml/kg•h-1. In both R group and N group, a small number of nerve cells exhibited pyknotic degeneration. More nerve cells with pyknotic degeneration were found in R group than in N group (P<0.001). At 48 h after surgery, there was a significant correlation between the abnormality of right hind limb and the degree of edema in sciatic nerve (P<0.01). Pyknotic degeneration of sciatic nerve increased after an infusion of 0.2% ropivacaine hydrochloride for 48 h, suggesting the neurotoxicity of ropivacaine. An infusion of 0.2% ropivacaine hydrochloride for 48 h may cause necrosis of skeletal muscle cells. The sciatic nerve edema would greatly affect the hindlimb motor while both pyknotic degeneration of sciatic nerve and skeletal muscle have little influence on the hindlimb movement. After an infusion of 0.2% ropivacaine hydrochloride for 48 h, the morphology of right atrium and brain tissues around the ventriculus tertius and medulla oblongata remained unchanged.

Preparation and controlled release of mesoporous MCM-41/propranolol hydrochloride composite drug.

PubMed

Zhai, Qing-Zhou

2013-01-01

This article used MCM-41 as a carrier for the assembly of propranolol hydrochloride by the impregnation method. By means of chemical analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and low-temperature N(2) adsorption-desorption at 77 K, the characterization was made for the prepared materials. The propranolol hydrochloride guest assembly capacity was 316.20 ± 0.31 mg/g (drug/MCM-41). Powder XRD test results indicated that during the process of incorporation, the frameworks of the MCM-41 were not destroyed and the crystalline degrees of the host-guest nanocomposite materials prepared still remained highly ordered. Characterization by SEM and TEM showed that the composite material presented spherical particle and the average particle size of composite material was 186 nm. FT-IR spectra showed that the MCM-41 framework existed well in the (MCM-41)-propranolol hydrochloride composite. Low-temperature nitrogen adsorption-desorption results at 77 K showed that the guest partially occupied the channels of the molecular sieves. Results of the release of the prepared composite drug in simulated body fluid indicated that the drug can release up to 32 h and its maximum released amount was 99.20 ± 0.11%. In the simulated gastric juice release pattern of drug, the maximum time for the drug release was discovered to be 6 h and the maximum cumulative released amount of propranolol hydrochloride was 45.13 ± 0.23%. The drug sustained-release time was 10 h in simulated intestinal fluid and the maximum cumulative released amount was 62.05 ± 0.13%. The prepared MCM-41 is a well-controlled drug delivery carrier.

[Influence of polymer type on the physical properties and the release study of papaverine hydrochloride from tablets].

PubMed

Kasperek, Regina; Polski, Andrzej; Sobótka-Polska, Karolina; Poleszak, Ewa

2014-01-01

Polymers are widely used in drug manufacturing. Researchers studied their impact on the bioavailability of active substances or on physical properties of tablets for many years. To study the influence of polymer excipients, such as microcrystalline cellulose (Avicel PH 101, Avicel PH 102), croscarmellose sodium, crospovidone or polyvinylpyrrolidone, on the release profile of papaverine hydrochloride from tablets and on the physical properties of tablets. Six series of uncoated tablets were prepared by indirect method, with previous wet granulation. Tablets contained papaverine hydrochloride and various excipients. The physical properties of the prepared granules, tablets and the release profile of papaverine hydrochloride from tablets were examined. The content of papaverine hydrochloride from the release study were determined spectrophotometrically. All tablets met the pharmacopoeia requirements during following tests: the disintegration time of tablets, uncoated tablets resistance to abrasion, the weight uniformity and dose formulations, their dimensions, the resistance to crushing of tablets and the drug substance content in the tablet. In four cases more than 80% of papaverine was released up to 2 min, in one formula it was up to 5 min, and in last one up to 10 min. Tablets containing crospovidone disintegrated faster than tablets with croscarmellose sodium. Adding gelatinized starch to the tablet composition increased the disintegration time, hardness and delayed the release of papaverine. During the wet granulation process, granules containing polyvinylpyrrolidone were characterized by a suitable flow properties and slightly prolonged disintegration time. Tablets containing Avicel PH 102 compared to tablets with Avicel PH 101 had less weight loss during the test of mechanical resistance, improved hardness and faster release profile of papaverine from tablets.

Simultaneous determination of rosuvastatin and propranolol in their binary mixture by synchronous spectrofluorimetry.

PubMed

El-Abasawi, Nasr M; Attia, Khalid A M; Abo-Serie, Ahmad A M; Morshedy, Samir; Abdel-Fattah, Ashraf

2018-06-05

Simultaneous determination of rosuvastatin calcium and propranolol hydrochloride using the first derivative synchronous spectrofluorimetry was described. This method involves measuring the synchronous fluorescence of both drugs in ethanol using, ∆ λ = 60 nm then the first derivative was recorded and the peak amplitudes were measured at 350 and 374 nm for rosuvastatin calcium and propranolol hydrochloride, respectively. Under the optimum conditions, the linear ranges of rosuvastatin calcium and propranolol hydrochloride were 0.2-2 μg/mL and 0.1-1 μg/mL, respectively. The method was used for quantitative analysis of the drugs in raw materials and pharmaceutical dosage form. The validity of the proposed method was assessed according to an international conference on harmonization (ICH) guidelines. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of genotoxic effects of Apitol (cymiazole hydrochloride) in vitro by measurement of sister chromatid exchange.

PubMed

Stanimirovic, Zoran; Stevanovic, Jevrosima; Jovanovic, Slobodan; Andjelkovic, Marko

2005-12-30

Apitol, with cymiazole hydrochloride as the active ingredient, is used in bee-keeping against the ectoparasitic mite Varroa destructor. The preparation was evaluated for genotoxicity in cultured human peripheral blood lymphocytes. Sister chromatid exchange, the mitotic index and the cell proliferation index were determined for three experimental concentrations of Apitol (0.001, 0.01 and 0.1 mg/ml). All concentrations significantly (p < 0.001) increased the mitotic index (MI = 7.35+/-0.18%, 8.31+/-0.20% and 12.33+/-0.25%, respectively), the proliferative index (PI = 1.83+/-0.01, 1.84+/-0.01 and 1.88+/-0.02, respectively) and the frequency of sister chromatid exchange (SCE = 8.19+/-1.81, 8.78+/-1.80 and 13.46+/-1.88, respectively), suggesting that cymiazole hydrochloride has genotoxic potential.

A Morphofunctional Study on the Effect of Cytochalasin B on Intestinal Water Transport.

DTIC Science & Technology

1986-05-10

Topic Category Selection hydrochloride . c. Signature Block for Member’s Signature d. Check Presentation Preference Box Each Abstract Form submitted...1999: 4-(2-isopropylamino-I-hydroxyethyl) methanesulfonanilide b. Topic Category Selection hydrochloride . c. Signature Block for Member’s Signature d...intestinal glyco- protein incorporation of 01-14 ) Glucosamine in vitro. Biochim Biophys Acta 261:353. Moe H (1955). On goblet cells, especially of

Synthesis of Nucleoside Analogues with Potential Antiviral Activity against Negative Strand RNA Virus Targets

DTIC Science & Technology

1989-11-01

standing overnight. Washing the filtered crystals with ether removed triethylamine hydrochloride and triphenyl phosphine, then recrystallisation from...pyridine to from an ester, DMF and pyridinium hydrochloride . The reaction of the Vilsmeier reagent with (E)-5-(2-carboxyvinyl)uridine and quenching...include 2-deoxy-2-glucose (28), D- glucosamine (29) and tunicamycin (30). Deoxyglucose is utilized instead of glucose in the formation of guanosine

Stress, Predictability, and Oral Fentanyl Self-Administration in Female and Male Rats

DTIC Science & Technology

1995-03-09

naloxone. When dissolved in water, fentanyl hydrochloride (Hel) is less bitter-tasting than morphine and it is readily self- administered by rats...and for assessment of the biochemical effects of the stressor. Drugs Fentanyl- hydrochloride (HCI) (NIDA, Baltimore, MD), in a concentration of 50...responses despite lower opioid SA, treatment for men might focus on pharmacologic replacement therapies, such as methadone maintenance programs. The

Drug Abuse and Criminal Violence in Urban Communities.

DTIC Science & Technology

1987-01-01

for smoking or freebasing. 6. Heroin: "Semisynthetic derivative of morphine. Chemical name is deacethylmorphine hydrochloride . Synthesized in 1898 in...is Sernyl. Chemical name is I-(l-phencyclohexyl) piperidine hydrochloride . Sold in the form of a white crystal or powder that can be injected, smoked...neurotransmitters... * - [. Usually sold in the form of capsules and tablets but also in powder or liquid form." 1 0 10. Methadone : "Synthetic narcotic less

Beliefs and Social Norms about Codeine and Promethazine Hydrochloride Cough Syrup (CPHCS) Onset and Perceived Addiction among Urban Houstonian Adolescents: An Addiction Trend in the City of Lean

ERIC Educational Resources Information Center

Peters, Ronald J., Jr.; Kelder, Steven H.; Markham, Christine M.; Yacoubian, George S., Jr.; Peters, LeCresha A.; Ellis, Artist

2003-01-01

In the current study, we used a qualitative approach to investigate relevant beliefs and norms associated with codeine and promethazine hydrochloride cough syrup (CPHCS) consumption, initiation, and perceived addiction among 48 alternative school students who identified themselves as current CPHCS users. In general, both boys and girls believed…

Assay of fluoxetine hydrochloride by titrimetric and HPLC methods.

PubMed

Bueno, F; Bergold, A M; Fröehlich, P E

2000-01-01

Two alternative methods were proposed to assay Fluoxetine Hydrochloride: a titrimetric method and another by HPLC using as mobile phase water pH 3.5: acetonitrile (65:35). These methods were applied to the determination of Fluoxetine as such or in formulations (capsules). The titrimetric method is an alternative for pharmacies and small industries. Both methods showed accuracy and precision and are an alternative to the official methods.

An evaluation of melarsomine hydrochloride efficacy for parasitological cure in experimental infection of dairy cattle with Trypanosoma evansi in Thailand.

PubMed

Desquesnes, Marc; Kamyingkird, Ketsarin; Vergne, Timothée; Sarataphan, Nachai; Pranee, Rodtian; Jittapalapong, Sathaporn

2011-08-01

Melarsomine hydrochloride can cure Trypanosoma evansi infection in camels at a dose of 0·25 mg/kg, but at that dose relapses occur in cattle. In our study, the efficacy of an intramuscular injection of melarsomine hydrochloride at 0·5 mg/kg was assessed in 3 normal and 3 splenectomized dairy cattle experimentally infected with a stock of T. evansi from Thailand. The animals were monitored for 5 months by haematocrit centrifugation, blood- or cerebrospinal fluid-mouse inoculation, polymerase chain reaction, the card agglutination test (CATT) for T. evansi, and the enzyme-linked immunosorbent assay‑T. evansi. Parasitological and DNA tests became and remained negative just after treatment. By the end of the experiment, CATT was negative and ELISA scores were below or very close to the cut-off value. One of the splenectomized cattle died from anaplasmosis during the experiment, but tested negative for surra. It was concluded that the parasites had been cleared from the cattle, and melarsomine hydrochloride at 0·5 mg/kg can be recommended for treatment against T. evansi infection in dairy cattle in Thailand. Further work is necessary to validate the efficacy of the treatment in the event of confirmed CSF-infection.

Mechanism of the Skraup and Doebner-von Miller quinoline syntheses: Cyclization of. alpha. ,. beta. -unsaturated N-aryliminium salts via 1,3-dizaetidinium ion intermediates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eisch, J.J.; Dluzniewski, T.

1989-03-17

The hydrochlorides of cinnamaldehyde anils of the type ArCH=CHCH=NAr{prime}, where Ar and Ar{prime} are phenyl or p-tolyl groups, have been shown to react between 25{degree}C and 100{degree}C, in a toluene suspension or in a solution of DMSO or acetonitrile, to yield 2-substituted quinolines and N-cinnamylanilines ArCH=CHCH{sub 2}NHAr{prime}. The reaction proceeds under anhydrous conditions by cyclization of the anil hydrochlorides themselves to produce ultimately 2-substituted quinolines. The kinetics of the reaction follow a first-order dependence on the anil hydrochloride. Rapid exchange occurring between dissimilar anil hydrochlorides suggests that such anil metatheses take place by way of 1,3-diazetidinium ion intermediates, which previousmore » studies have shown would possess the requisite metastability. The foregoing experimental observations are reconciled in terms of a novel mechanism for the formation of quinolines directly from anils under acidic conditions, namely, the reversible formation of diazetidinium ions and their irreversible cyclization to quinolines. It is proposed that this pathway is the operative mechanism in the classic Skraup and Doehner-von Miller quinoline syntheses. 28 refs., 2 tabs.« less

The Risk of Microbial Contamination in Multiple-Dose Preservative-Free Ophthalmic Preparations.

PubMed

Saisyo, Atsuyuki; Shimono, Rima; Oie, Shigeharu; Kimura, Kazuhiro; Furukawa, Hiroyuki

2017-01-01

Multiple-dose ophthalmic preparations that do not contain preservatives carry high risks of microbial contamination. However, there are various types of hospital preparations, with different physicochemical properties. In the present study, we evaluated the association between physicochemical properties and microbial contamination in ophthalmic preparations. The investigated hospital preparations included ophthalmic preparations of physiological saline, 0.2% fluconazole, 0.5% vancomycin hydrochloride, and 2% cyclosporine. We investigated the microbial dynamics of each ophthalmic preparation and microbial contamination in ophthalmic preparations used by patients. Remarkable growth of Pseudomonas aeruginosa, Burkholderia cepacia, and Serratia marcescens was observed in ophthalmic preparations of physiological saline and 0.2% fluconazole. All tested microorganisms displayed decreased counts after inoculation in 0.5% vancomycin hydrochloride. In 2% cyclosporine, all investigated microorganisms were below the limit of detection after inoculation for 6 h. The microbial contamination rates of ophthalmic preparations used by patients were 16.7% (3/18 samples) for 0.5% vancomycin hydrochloride and 0% (0/30 samples) for 2% cyclosporine. All detected contaminants in 0.5% vancomycin hydrochloride were Candida spp., one of which was present at a level of 1×10 4 colony-forming units/mL. The storage method for in-use ophthalmic preparations should be considered on the basis of their physicochemical properties.

Silicone adhesive matrix of verapamil hydrochloride to provide pH-independent sustained release.

PubMed

Tolia, Gaurav; Li, S Kevin

2014-02-01

Providing pH-independent oral release of weakly basic drugs with conventional matrix tablets can be challenging because of the pH-dependent solubility characteristics of the drugs and the changing pH environment along the gastrointestinal tract. The aim of the present study was to use a hydrophobic polymer to overcome the issue of pH-dependent release of weakly basic model drug verapamil hydrochloride from matrix tablets without the use of organic buffers in the matrix formulations. Silicone pressure-sensitive adhesive (PSA) polymer was evaluated because of its unique properties of low surface energy, hydrophobicity, low glass transition temperature, high electrical resistance, and barrier to hydrogen ion diffusion. Drug release, hydrogen ion diffusion, tablet contact angle, and internal tablet microenvironment pH with matrix tablets prepared using PSA were compared with those using water-insoluble ethyl cellulose (EC). Silicone PSA films showed higher resistance to hydrogen ion diffusion compared with EC films. Verapamil hydrochloride tablets prepared using silicone PSA showed higher hydrophobicity and lower water uptake than EC tablets. Silicone PSA tablets also showed pH-independent release of verapamil and decreased in dimensions during drug dissolution. By contrast, verapamil hydrochloride tablets prepared using EC did not achieve pH-independent release.

Formulation of bi-layer matrix tablets of tramadol hydrochloride: Comparison of rate retarding ability of the incorporated hydrophilic polymers.

PubMed

Arif, Hasanul; Al-Masum, Abdullah; Sharmin, Florida; Reza, Selim; Sm Islam, Sm Ashraful

2015-05-01

Bi-layer tablets of tramadol hydrochloride were prepared by direct compression technique. Each tablet contains an instant release layer with a sustained release layer. The instant release layer was found to release the initial dose immediately within minutes. The instant release layer was combined with sustained release matrix made of varying quantity of Methocel K4M, Methocel K15MCR and Carbomer 974P. Bi-layer tablets were evaluated for various physical tests including weight variation, thickness and diameter, hardness and percent friability. Drug release from bi-layer tablet was studied in acidic medium and buffer medium for two and six hours respectively. Sustained release of tramadol hydrochloride was observed with a controlled fashion that was characteristic to the type and extent of polymer used. % Drug release from eight-hour dissolution study was fitted with several kinetic models. Mean dissolution time (MDT) and fractional dissolution values (T25%, T50% and T80%) were also calculated as well, to compare the retarding ability of the polymers. Methocel K15MCR was found to be the most effective in rate retardation of freely water-soluble tramadol hydrochloride compared to Methocel K4M and Capbomer 974P, when incorporated at equal ratio in the formulation.

Topical anesthesia with benoxinate 0.4% for pterygium surgery.

PubMed

Frucht-Pery, J

1997-03-01

Anesthesia during pterygium surgery is usually achieved with injections of anesthetic medications. This study evaluated the efficacy of topical anesthesia with benoxinate hydrochloride 0.4% for pterygium surgery. One hundred fifty consecutive patients who had primary or recurrent pterygium underwent surgical excision of the lesion. Before the surgical procedure began, each eye that was operated on received 1 drop of benoxinate hydrochloride 0.4% solution every 1 minute for 10 minutes. The pain sensation was tested with 0.12 forceps. The pterygium was dissected, and 1 or 2 conjunctival sutures were placed, leaving bare sclera. Drops of benoxinate hydrochloride 0.4% were added every 5 minutes during the operation. The average pterygium excision time in this study was 25 minutes. Of the 150 patients studied, only 3 required intraoperative injection of lignocaine 1%. In 2 cases, subconjunctival injection was performed, and in 1 case, retrobulbar injection was required to complete the procedure. Of the remaining 147 patients, 115 had discomfort or mild pain and asked for more anesthetics once or twice during the procedure. Postoperatively, the wounds epithelialized within 7 to 14 days in all patients, except for 2 who had postoperative dellen and 2 who received mitomycin-C postoperatively. Topical administration of benoxinate hydrochloride 0.4% provides useful anesthesia for pterygium surgery.

Eye drops preservative as the cause of corneal band keratopathy in long-term pilocarpine hydrochloride treatment.

PubMed

Pavicić-Astalos, Jasna; Lacmanović-Loncar, Valentina; Petric-Vicković, Ivanka; Sarić, Dean; Mandić, Zdravko; Csik, Tigrena; Susić, Nikola

2012-03-01

The aim is to present a patient with severe bilateral corneal complications after long-term antiglaucoma treatment with 1% pilocarpine hydrochloride (Pilokarpin, Pliva, Zagreb, Croatia) and its management. A patient with narrow-angle glaucoma treated with 1% topical pilocarpine hydrochloride eye drops for the last twenty years complained of impaired vision, intermittent visual haloes and eye redness. Ophthalmologic examination showed bilateral band keratopathy, peripheral laser iridotomy, medicamentous myosis, brown nuclear cataract, and synchysis scintillans of his right eye. Band keratopathy was thought to have resulted from the presence of the preservative phenylmercuric nitrate in the pilocarpine hydrochloride eye drops. Treatment of the patient consisted of two separate procedures for both eyes, i.e. phaco trabeculectomy and six months later corneal procedure including abrasion of corneal epithelium followed by removal of the superficial stromal calcium deposits by means of a 3.75% ethylenediaminetetraacetic (EDTA) solution. After phaco trabeculectomy, visual acuity was 0.8 on both eyes. Bilateral visual improvement with visual acuity 1.0 was recorded after corneal treatment with EDTA. In conclusion, one must be aware of preservative complications in long-term topical use, such as band keratopathy that can be visually incapacitating. Surgical treatment using EDTA is safe and effective treatment for band keratopathy.

Determination of antazoline hydrochloride in rat plasma and excreta by reversed-phase ion-pair chromatography and its application to pharmacokinetics.

PubMed

Wang, Rui; Chu, Yanle; Li, Xiaotian; Wan, Baoluo; Yu, Tong; Wang, Linxi; Hao, Lianqi; Guo, Maowen

2013-12-01

A reversed-phase ion pair chromatography method with liquid-liquid extraction analytical method was developed and validated for the determination of antazoline hydrochloride in plasma and excreta of rat. The aim of our study was to characterize the preclinical pharmacokinetics and excretion profiles of antazoline hydrochloride in rats after intravenous injection at the dose of 10 mg/kg. Plasma and excreta samples were extracted with ethyl acetate, and phenacetin was used as the internal standard. The result showed that the method is suitable for the quantification of antazoline hydrochloride in plasma and excreta samples. Analysis of accuracy (90.89-112.33%), imprecision (<7.1%) and recovery (>82.5%) showed adequate values. After a single intravenous administration at 10 mg/kg to rats, plasma concentration profile showed a relative fast elimination proceeding with a terminal elimination half-life of 3.53 h. Approximately 61.8 and 14.2% of the administered dose were recovered in urine and bile after 72 and 24 h post-dosing respectively; 5.9% of the administered dose was recovered in feces after 72 h post-dosing. The above results show that the major elimination route is urinary excretion. Copyright © 2013 John Wiley & Sons, Ltd.

Neuroleptic malignant syndrome possibly caused by molindone hydrochloride.

PubMed

Gradon, J D

1991-10-01

The case of a patient who developed neuroleptic malignant syndrome (NMS) on three separate occasions is presented. Her third bout of this syndrome possibly was caused by molindone hydrochloride. This medication has been reported only once previously to cause NMS. The pharmacology of molindone is reviewed and a complicating factor in this case--the recent onset of hypothyroidism--is discussed together with its implication in the development of the clinical manifestations of this syndrome.

Evaluation of safety of lipomer doxycycline hydrochloride (lipomer DH).

PubMed

Dhumal, Rohit; Soni, Mahesh; Devarajan, Padma; Samad, Abdul; Gaikwad, Rajiv; Vanage, Geeta

2011-02-01

The nanoparticulate formulation of lipomer doxycycline hydrochloride (lipomer DH) has been synthesized for the treatment of Brucellosis to increase efficacy of the drug. The present study was undertaken to determine the intravenous safety of blank lipomer and Lipomer DH in terms of maximum tolerated dose in rats. It was observed that blank lipomer and lipomer DH were safe when administered intravenously at doses 2000 mg/kg Bw and 18 mg/kg bw respectively.

40 CFR Appendix A to Subpart Ddd... - Free Formaldehyde Analysis of Insulation Resins by the Hydroxylamine Hydrochloride Method

Code of Federal Regulations, 2013 CFR

2013-07-01

... buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3.4Magnetic stirrer and stir bars. 3.5250-mL beaker... N sodium hydroxide solution. 4.2Hydroxylamine hydrochloride solution, 100 grams per liter, pH... prestandardized pH meter, 1.0 N hydrochloric acid, 0.1 N hydrochloric acid, and 0.1 N sodium hydroxide. 5.5Add 50...

40 CFR Appendix A to Subpart Ddd... - Free Formaldehyde Analysis of Insulation Resins by the Hydroxylamine Hydrochloride Method

Code of Federal Regulations, 2012 CFR

2012-07-01

... buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3.4Magnetic stirrer and stir bars. 3.5250-mL beaker... N sodium hydroxide solution. 4.2Hydroxylamine hydrochloride solution, 100 grams per liter, pH... prestandardized pH meter, 1.0 N hydrochloric acid, 0.1 N hydrochloric acid, and 0.1 N sodium hydroxide. 5.5Add 50...

40 CFR Appendix A to Subpart Ddd... - Free Formaldehyde Analysis of Insulation Resins by the Hydroxylamine Hydrochloride Method

Code of Federal Regulations, 2014 CFR

2014-07-01

... buffer. 3.350-mL burette for 1.0 N sodium hydroxide. 3.4Magnetic stirrer and stir bars. 3.5250-mL beaker... N sodium hydroxide solution. 4.2Hydroxylamine hydrochloride solution, 100 grams per liter, pH... prestandardized pH meter, 1.0 N hydrochloric acid, 0.1 N hydrochloric acid, and 0.1 N sodium hydroxide. 5.5Add 50...

Simultaneous determination of rabeprazole sodium and itopride hydrochloride in capsule dosage form by spectrophotometry.

PubMed

Sabnis, Shweta S; Gandhi, Santosh V; Madgulkar, A R; Bothara, K G

Three methods viz. Absorbance Ratio Method (I), Dual Wavelength Method (II) and First Order Derivative Spectroscopic Method (III) for simultaneous estimation of Rabeprazole sodium and Itopride hydrochloride have been developed. The drugs obey Beer's law in the concentration range 2-20 microg/ml for RAB and 5-75 microg/ml for ITO. The results of analysis of drugs have been validated statistically and by recovery studies.

Suicide Inhibitors of Reverse Transcriptase in the Therapy of AIDS and Other Retroviruses

DTIC Science & Technology

1991-07-01

of intermediate 3 was detected by 3 P NMR spectroscopy . The observed chemical shifts are comparable to those reported ’in the literature. The spectrum...were characterized by NMR spectroscopy . The presence of the characteristic triphosphate group was confirmed by NMR as indicated in the figure below...Two compounds, 2𔃽’ sulfinyl cytidine hydrochloride and 2,0 2 anhydrocytidine hydrochloride, which have proved to be highly effective against vaccinia

Disposable screen-printed sensors for determination of duloxetine hydrochloride

PubMed Central

2012-01-01

A screen-printed disposable electrode system for the determination of duloxetine hydrochloride (DL) was developed using screen-printing technology. Homemade printing has been characterized and optimized on the basis of effects of the modifier and plasticizers. The fabricated bi-electrode potentiometric strip containing both working and reference electrodes was used as duloxetine hydrochloride sensor. The proposed sensors worked satisfactorily in the concentration range from 1.0 × 10-6-1.0 × 10-2 mol L-1 with detection limit reaching 5.0 × 10-7 mol L-1 and adequate shelf life of 6 months. The method is accurate, precise and economical. The proposed method has been applied successfully for the analysis of the drug in pure and in its dosage forms. In this method, there is no interference from any common pharmaceutical additives and diluents. Results of the analysis were validated statistically by recovery studies. PMID:22264225

The effect of polymorphism on powder compaction and dissolution properties of chemically equivalent oxytetracycline hydrochloride powders.

PubMed

Liebenberg, W; de Villiers, M M; Wurster, D E; Swanepoel, E; Dekker, T G; Lötter, A P

1999-09-01

In South Africa, oxytetracycline is identified as an essential drug; many generic products are on the market, and many more are being developed. In this study, six oxytetracycline hydrochloride powders were obtained randomly from manufacturers, and suppliers were compared. It was found that compliance to a pharmacopoeial monograph was insufficient to ensure the optimum dissolution performance of a simple tablet formulation. Comparative physicochemical raw material analysis showed no major differences with regard to differential scanning calorimetry (DSC), infrared (IR) spectroscopy, powder dissolution, and particle size. However, the samples could be divided into two distinct types with respect to X-ray powder diffraction (XRD) and thus polymorphism. The two polymorphic forms had different dissolution properties in water or 0.1 N hydrochloride acid. This difference became substantial when the dissolution from tablets was compared. The powders containing form A were less soluble than that containing form B.

Delivery of prazosin hydrochloride from osmotic pump system prepared by coating the core tablet with an indentation.

PubMed

Liu, Longxiao; Wang, Jinchao; Zhu, Suyan

2007-04-01

The preparation of an osmotic pump tablet was simplified by elimination of laser drilling using prazosin hydrochloride as the model drug. The osmotic pump system was obtained by coating the indented core tablet compressed by the punch with a needle. A multiple regression equation was achieved with the experimental data of core tablet formulations, and then the formulation was optimized. The influences of the indentation size of the core tablet, environmental media, and agitation rate on drug release profile were investigated. The optimal osmotic pump tablet was found to deliver prazosin hydrochloride at an approximately constant rate up to 24 hr, and independent on both release media and agitation rate. Indentation size of core tablet hardly affected drug release in the range of 0.80-1.15 mm. The method that is simplified by elimination of laser drilling may be promising for preparation of an osmotic pump tablet.

Concerns about the safety of obesity agents from a manufacturing perspective.

PubMed

Kanfer, Isadore

2008-07-01

Salt derivatives of active pharmaceutical ingredients (API), such as hydrochloride and mesylate salts, are frequently used during drug product development. Compared with the underivatized API, salt derivatives are often associated with beneficial properties, including improved solubility and better absorption. Although the obesity agent sibutramine was initially approved as the hydrochloride salt, it has also been formulated as a mesylate salt (sibutramine mesylate). In order to qualify as interchangeable, generic products generally must be both pharmaceutically equivalent and bioequivalent to an approved reference product. Because generic versions of hydrochloride salt formulations that have been reformulated as mesylate salts are not pharmaceutically equivalent to the approved reference products, they would not be interchangeable, even if bioequivalent. The safety of APIs and drug products manufactured outside the United States in non-Food and Drug Administration-regulated facilities are of concern, particularly agents that may contain harmful impurities, such as obesity products formulated as mesylate salts.

Esterification of pseudoephedrine hydrochloride by citric acid in a solid dose pharmaceutical preparation.

PubMed

Goel, Alok; Zhao, Zhicheng; Sørensen, Dan; Zhou, Jay; Zhang, Fa

2016-09-10

Esterification of pseudoephedrine hydrochloride (PSE) by citric acid was observed in a solid dose pharmaceutical preparation at room temperature and accelerated stability condition (40°C/75% relative humidity). The esterification of PSE with citric acid was confirmed by a solid-state binary reaction in the presence of minor level of water at elevated temperature to generate three isomeric esters. The structures of the pseudoephedrine citric acid esters were elucidated using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy (NMR). Occurrence of esterification in solid state, instead of amidation which is generally more favorable than esterification, is likely due to remaining HCl salt form of solid pseudoephedrine hydrochloride to protect its amino group from amidation with citric acid. In contrast, the esterification was not observed from solution reaction between PSE and citric acid. Copyright © 2016 Elsevier B.V. All rights reserved.

Tear thinning time and topical anesthesia as assessed using the HIRCAL grid and the NCCA.

PubMed

Blades, K J; Murphy, P J; Patel, S

1999-03-01

The literature contains conflicting reports of the effects of topical anesthetics on tear film stability, with some consensus that unpreserved topical anesthetics are less likely to reduce tear film stability than preserved preparations. This experiment investigated the effect of unpreserved 0.4% benoxinate hydrochloride on tear thinning time (TTT), in parallel with "real time" corneal sensitivity assessment. Tear film stability was assessed (HIRCAL grid) in parallel with real time assessment of the pharmacological activity (NCCA) of unpreserved 0.4% benoxinate hydrochloride in normal eyes. The anesthetic used did not significantly affect tear film stability. This finding is in agreement with previous investigators. Unpreserved 0.4% benoxinate hydrochloride could be used to facilitate tear film stability assessment. The experimental protocol used could also be applied to investigate the temporal relationship between anesthesia and tear film stability with preserved topical anesthetics that have been found to decrease tear film stability.

Quantitative estimation of itopride hydrochloride and rabeprazole sodium from capsule formulation.

PubMed

Pillai, S; Singhvi, I

2008-09-01

Two simple, accurate, economical and reproducible UV spectrophotometric methods and one HPLC method for simultaneous estimation of two component drug mixture of itopride hydrochloride and rabeprazole sodium from combined capsule dosage form have been developed. First developed method involves formation and solving of simultaneous equations using 265.2 nm and 290.8 nm as two wavelengths. Second method is based on two wavelength calculation, wavelengths selected for estimation of itopride hydrochloride was 278.0 nm and 298.8 nm and for rabeprazole sodium 253.6 nm and 275.2 nm. Developed HPLC method is a reverse phase chromatographic method using phenomenex C(18) column and acetonitrile: phosphate buffer (35:65 v/v) pH 7.0 as mobile phase. All developed methods obey Beer's law in concentration range employed for respective methods. Results of analysis were validated statistically and by recovery studies.

Quantitative Estimation of Itopride Hydrochloride and Rabeprazole Sodium from Capsule Formulation

PubMed Central

Pillai, S.; Singhvi, I.

2008-01-01

Two simple, accurate, economical and reproducible UV spectrophotometric methods and one HPLC method for simultaneous estimation of two component drug mixture of itopride hydrochloride and rabeprazole sodium from combined capsule dosage form have been developed. First developed method involves formation and solving of simultaneous equations using 265.2 nm and 290.8 nm as two wavelengths. Second method is based on two wavelength calculation, wavelengths selected for estimation of itopride hydrochloride was 278.0 nm and 298.8 nm and for rabeprazole sodium 253.6 nm and 275.2 nm. Developed HPLC method is a reverse phase chromatographic method using phenomenex C18 column and acetonitrile: phosphate buffer (35:65 v/v) pH 7.0 as mobile phase. All developed methods obey Beer's law in concentration range employed for respective methods. Results of analysis were validated statistically and by recovery studies. PMID:21394269

Determination of itopride hydrochloride by high-performance liquid chromatography with Ru(bpy)3(2+) electrogenerated chemiluminescence detection.

PubMed

Sun, Yonghua; Zhang, Zhujun; Xi, Zhijun; Shi, Zuolong; Tian, Wei

2009-08-26

In this work, a stable electrogenerated chemiluminescence (ECL) detector was developed. The detector was prepared by packing cation-exchanged resin particles in a glass tube, followed by inserting Pt wires (working electrode) in this tube and sealing. The leakage of Ru(bpy)(3)(2+) can be compensated by adding a small amount of Ru(bpy)(3)(2+) into solution phase. Coupled with high-performance liquid chromatography separation, the detector has been used for determination of itopride hydrochloride in human serum. Under the optimal conditions, the ECL intensity has a linear relationship with the concentration of itopride hydrochloride in the range of 1.0 x 10(-8) g mL(-1) to 1.0 x 10(-6) g mL(-1) and the detection limit was 3 x 10(-9) g mL(-1) (S/N=3). The as-prepared ECL detector displayed good sensitivity and stability.