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1

Analgesic efficacy and potency of two oral controlled-release morphine preparations  

Microsoft Academic Search

MS Contin tablets and Oramorph SR tablets are two forms of oral controlled-release morphine sulfate available for the alleviation of pain. Our objective was to compare their analgesic effects in a relative potency assay. In this study, 151 patients undergoing caesarean section or abdominal hysterectomy and reporting moderate or severe postoperative pain received a 30 or 90 mg dose of

Saul S Bloomfield; Gail B Cissell; Jeanette Mitchell; Tom P Barden; Robert F Kaiko; Ronald D Fitzmartin; Robert P Grandy; James Komorowski; Paul D Goldenheim

1993-01-01

2

Peak plasma concentrations after oral morphine: a systematic review.  

PubMed

We performed a systematic review of 69 studies with information on 2146 subjects (454 patients and 1692 healthy volunteers) to examine the maximum plasma concentration (Cmax) and the time taken to reach maximum concentration (Tmax) for different oral morphine formulations, and to clarify factors contributing to variability. Data from healthy volunteers reflected that seen for patients but was less variable. There was minimal difference between single and multiple doses, suggesting no accumulation of morphine. For immediate-release morphine there was no difference in either dose-corrected Cmax or Tmax between solution and tablets, or between different salts. For controlled-release formulations, little difference was observed between brands. Only for once-daily formulations was there any difference in absorption between fed and fasted, with a Tmax for fed subjects considerably longer than for fasted. There was no evidence for any difference between values obtained by radioimmunoassay (RIA) or high-performance liquid chromatography (HPLC). PMID:9879164

Collins, S L; Faura, C C; Moore, R A; McQuay, H J

1998-12-01

3

Use of Sustained Release Oral Morphine as a Bridge in Withdrawal of Morphine in Patients on High Doses of Oral Immediate Release Morphine for Cancer Pain  

Microsoft Academic Search

According to World Health Organization (WHO), cancer pain can be controlled effectively with oral morphine in up to 90% of patients. Due to advancement in anticancer therapy and early presentation of cancer patients, the likelihood of cure is on an increasing trend. Awareness and education in the use of oral morphine, and easier regulations in procurement of oral morphine for

Arif Ahmed; Himanshu Khurana; Vikas Gogia; Seema Mishra; Sushma Bhatnagar

2010-01-01

4

Oral bioavailability of mesna tablets  

Microsoft Academic Search

To test the feasibility of uroprotection with sodium 2-mercaptoethane-sulfonate (mesna) in tablet form the bioavailability of mesna tablets was determined in healthy volunteers by HPLC. The area under the plasma concentration-time curve (AUC) of free mesna was significantly lower following oral (110 µmol.l-1.h-1; 95% CI 98–122) than following i.v. administration of 1.2 g of mesna (201 µmol.l-1.h-1; 95% CI 158–244).

Brigitte Stofer-Vogell; Thomas Cerny; Markus Borner; Bernhard H. Lauterburgl

1993-01-01

5

Oral Morphine Prescribing Practices in Severe Cancer Pain  

PubMed Central

Background: Nearly one million cancer patients in India need oral morphine for pain relief. Despite doctors prescribing oral morphine in our center, many cancer patients with severe pain found to be not facilitated with adequate pain relief. Aim: This audit was conducted to look at the “oral morphine prescribing practices for severe cancer pain” at a tertiary care hospital. Materials and Methods: Twenty case files of patients, who were admitted with severe cancer pain, and receiving oral morphine were analyzed in pre- and posteducational session. Local standards were set to assess the adequacy of pain relief. Deficiency in achieving analgesia was found in preinterventional audit. A clinical audit was conducted before and after the educational session on oral morphine prescribing. The education for doctors and nurses focused on starting patients on morphine, titration, and administering rescue dose. Then local guidelines on oral morphine prescribing were circulated. And analysis of following factors were done following pre- and posteducational session: Pain intensity at the beginning of treatment, starting dose of morphine, increments in morphine dose, number of rescue doses given, and fall in pain intensity at the end of 1 week. The outcomes were compared with the standards. Results: Preintervention audit showed that only 50% of patients achieved adequate pain relief. Rescue dose was administered in only 20% of patients. While reaudit following the educational session showed that 80% of patients achieved adequate pain relief and 100% received rescue doses. Conclusion: Educational sessions have significant impact on improving oral morphine prescribing practice among doctors and nurses. It was found failing to administer regular as well as rescue doses resulted in inadequate pain relief in patients receiving oral morphine. PMID:20668591

B, Barathi

2009-01-01

6

Rifampin reduces oral morphine absorption: a case of transdermal buprenorphine selection based on morphine pharmacokinetics.  

PubMed

A 51-year-old male was referred to the Stratton Veterans Affairs Medical Center Pain Service after hospital admission for endocarditis with a history of heroin use and chronic low back pain. During his hospital stay he experienced a reduction in his serum morphine level ostensibly as a result of concomitant rifampin administration. We hypothesize that diminished absorption was from rifampin-mediated intestinal P-glycoprotein induction, ultimately decreasing serum free morphine and metabolites. The case became more complex in an attempt to balance managed pain, history of substance abuse, completion of antibiotic therapy, and a reasonable pain regimen upon discharge. Ultimately, the patient was titrated onto a buprenorphine transdermal patch, the initiation of which was based on serum free morphine and an extrapolated oral morphine dose by calculation. PMID:23216174

Fudin, Jeffrey; Fontenelle, Dania Vanesta; Payne, Annette

2012-12-01

7

Kollidon ® SR colloidal particles as vehicles for oral morphine delivery in pain treatment  

Microsoft Academic Search

Due to the great importance of new therapeutic routes for morphine in pain treatment, several investigations are under development. In this way, the design of a liquid system for the oral administration of morphine would be of great help, especially in patients with difficulties in swallowing (children and elderly people). The systems studied in this work are kollidon® SR microparticles,

José L. Arias; Amparo Gómez-Gallo; Ángel V. Delgado

2009-01-01

8

Oral Morphine Overdose in a Cancer Patient Antagonized by Prolonged Naloxone Infusion  

Microsoft Academic Search

An 80-year-old male was diagnosed with carcinoma in the lung with multiple bony metastases and had been prescribed pain medications as per World Health Organization analgesic ladder guidelines. However, he was not getting adequate pain relief and there were difficulties in titration of the morphine doses on an outpatient basis. Therefore, he was hospitalized for dose titration of oral morphine

Surjya Upadhyay; Roopesh Jain; Himanshu Chauhan; Deepak Gupta; Seema Mishra; Sushma Bhatnagar

2008-01-01

9

[Fast-disintegration oral tablets having sustained release property].  

PubMed

Fast-disintegrating (FD) tablets containing nicorandil-loaded dry emulsions were prepared and their controlled-release properties were examined and compared with the plain FD tablets (FD tablets without dry emulsions) and commercial tablets. The dry emulsions were prepared with myristyl alcohol and stearyl alcohol and their property was modified by mixing the ratio of the two alcohols. Disintegration time of the prepared FD tablets was sufficiently fast (i.e., 12 to 23 s). In vitro release of nicorandil from the FD tablets containing the dry emulsions was sustained over 6 h, while that from plain FD and commercial tablets was complete within 5 min. In vivo absorption of nicorandil from the tablets was evaluated by oral administration in beagle dogs. FD tablets containing dry emulsions showed a similar AUC, lower Cmax, and delayed Tmax compared to the plain FD and commercial tablets. These results suggest that the dry emulsion-loaded FD tablets can be utilized to improve the sustained-release property of active drugs. PMID:12440156

Jin, Yi; Ohkuma, Hideki; Wang, Hua; Natsume, Hideshi; Sugibayashi, Kenji; Morimoto, Yasunori

2002-11-01

10

Start of oral morphine to cancer patients: effective serum morphine concentrations and contribution from morphine-6-glucuronide to the analgesia produced by morphine  

Microsoft Academic Search

Objective: To investigate the serum concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) and the\\u000a relationships between serum concentrations and clinical effects associated with start of morphine treatment in cancer patients.\\u000a \\u000a \\u000a \\u000a Methods: Forty patients with malignant disease and intolerable pain on weak opioids (codeine\\/dextropropoxyphen) were included. After\\u000a a wash-out period, titration with immediate-release (IR) morphine was started. When a stable

P. Klepstad; S. Kaasa; P. C. Borchgrevink

2000-01-01

11

Morphine and codeine in oral fluid after controlled poppy seed administration.  

PubMed

Opiates are an important drug class in drug testing programmes. Ingestion of poppy seeds containing morphine and codeine can yield positive opiate tests and mislead result interpretation in forensic and clinical settings. Multiple publications evaluated urine opiate concentrations following poppy seed ingestion, but only two addressed oral fluid (OF) results; neither provided the ingested morphine and codeine dosage. We administered two 45?g raw poppy seed doses, each containing 15.7?mg morphine and 3.1?mg codeine, 8?h apart to 17 healthy adults. All OF specimens were screened by on-site OF immunoassay Draeger DrugTest 5000, and confirmed with OF collected with Oral-Eze® device and quantified by liquid chromatography-tandem mass spectrometry (1?µg/L morphine and codeine limits of quantification). Specimens (n?=?459) were collected before and up to 32?h after the first dose. All specimens screened positive 0.5?h after dosing and remained positive for 0.5-13?h at Draeger 20?µg/L morphine cut-off. Maximum OF morphine and codeine concentrations (Cmax ) were 177 and 32.6?µg/L, with times to Cmax (Tmax ) of 0.5-1?h and 0.5-2.5?h post-dose, respectively. Windows of detection after the second dose extended at least 24?h for morphine and to 18?h for codeine. After both doses, the last morphine positive OF result was 1?h with 40?µg/L 2004 proposed US Substance Abuse and Mental Health Services Administration cut-off, and 0.5?h with 95?µg/L cut-off, recently recommended by the Driving under the Influence of Drugs and Medicines project. Positive OF morphine results are possible 0.5-1?h after ingestion of 15.7?mg of morphine in raw poppy seeds, depending on the cut-off employed. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25345619

Concheiro, Marta; Newmeyer, Matthew N; da Costa, Jose Luiz; Flegel, Ron; Gorelick, David A; Huestis, Marilyn A

2014-10-24

12

Oral administration of morphine versus ibuprofen to manage postfracture pain in children: a randomized trial  

PubMed Central

Background: Recent warnings from Health Canada regarding codeine for children have led to increased use of nonsteroidal anti-inflammatory drugs and morphine for common injuries such as fractures. Our objective was to determine whether morphine administered orally has superior efficacy to ibuprofen in fracture-related pain. Methods: We used a parallel group, randomized, blinded superiority design. Children who presented to the emergency department with an uncomplicated extremity fracture were randomly assigned to receive either morphine (0.5 mg/kg orally) or ibuprofen (10 mg/kg) for 24 hours after discharge. Our primary outcome was the change in pain score using the Faces Pain Scale — Revised (FPS-R). Participants were asked to record pain scores immediately before and 30 minutes after receiving each dose. Results: We analyzed data from 66 participants in the morphine group and 68 participants in the ibuprofen group. For both morphine and ibuprofen, we found a reduction in pain scores (mean pre–post difference ± standard deviation for dose 1: morphine 1.5 ± 1.2, ibuprofen 1.3 ± 1.0, between-group difference [?] 0.2 [95% confidence interval (CI) ?0.2 to 0.6]; dose 2: morphine 1.3 ± 1.3, ibuprofen 1.3 ± 0.9, ? 0 [95% CI ?0.4 to 0.4]; dose 3: morphine 1.3 ± 1.4, ibuprofen 1.4 ± 1.1, ? ?0.1 [95% CI ?0.7 to 0.4]; and dose 4: morphine 1.5 ± 1.4, ibuprofen 1.1 ± 1.2, ? 0.4 [95% CI ?0.2 to 1.1]). We found no significant differences in the change in pain scores between morphine and ibuprofen between groups at any of the 4 time points (p = 0.6). Participants in the morphine group had significantly more adverse effects than those in the ibuprofen group (56.1% v. 30.9%, p < 0.01). Interpretation: We found no significant difference in analgesic efficacy between orally administered morphine and ibuprofen. However, morphine was associated with a significantly greater number of adverse effects. Our results suggest that ibuprofen remains safe and effective for outpatient pain management in children with uncomplicated fractures. Trial registration: ClinicalTrials.gov, no. NCT01690780. PMID:25349008

Poonai, Naveen; Bhullar, Gina; Lin, Kangrui; Papini, Adam; Mainprize, David; Howard, Jocelyn; Teefy, John; Bale, Michelle; Langford, Cindy; Lim, Rodrick; Stitt, Larry; Rieder, Michael J.; Ali, Samina

2014-01-01

13

The Quantitative Determinations of Glycyrrhizic Acid, Glycyrrhetinic Acid, Morphine, and Sodium Benzoate in Compound Liquorice Tablets by HPCE  

Microsoft Academic Search

Capillary zone electrophoresis (CZE) was used to quantitatively determine the contents of glycyrrhizic acid, glycyrrhetinic acid, morphine, and sodium benzoate in compound liquorice tablets. The detection wavelength was 228 nm and 14 kV voltage was applied, and the 50 mM sodium borate was used as the background electrolyte, in which hydrochlorothiazide served as an internal standard and the temperature was 24–25°C. There were

Guoxiang Sun; Yu Wang; Yuqing Sun

2003-01-01

14

Subjective, psychomotor, and analgesic effects of oral codeine and morphine in healthy volunteers  

Microsoft Academic Search

The subjective, psychomotor, and physiological effects of analgesic doses of oral codeine and morphine were examined in 12\\u000a healthy volunteers. Subjects ingested placebo, morphine 20 or 40?mg, or codeine 60 or 120?mg in a randomized, double-blind,\\u000a crossover design. The smaller and larger doses of each drug were putatively equianalgesic, and the cold-pressor test was included\\u000a to test this assumption. Codeine

D. J. Walker; James P. Zacny

1998-01-01

15

Fast disintegrating tablets of nisoldipine for intra-oral administration.  

PubMed

Nisoldipine is a calcium channel blocker with low and variable oral bioavailability. This was attributed to slow dissolution and presystemic metabolism. Accordingly, the objective of this work was to enhance the dissolution rate of nisoldipine to formulate fast disintegrating tablets with rapid dissolution. Binary solid dispersions (SD) were prepared for the drug with hydroxypropyl methyl cellulose E5 (HPMC), polyvinylpyrrolidone (PVP), Pluronic F68 or polyethylene glycol 6000 (PEG 6000). SD formation increased the dissolution rate compared to pure drug with the corresponding physical mixtures failing to provide the same dissolution enhancement. This indicates that the SD enhanced dissolution is not due to the solubilizing effect of the polymer and can be due to physical change in the drug crystal which was confirmed by thermal analysis. SD with HPMC and PVP were selected for preparation of fast disintegrating tablets as they liberated most of the drug in the first 5?min. HPMC-based tablets disintegrated rapidly and released most of the drug in the first 2?min which correlated with the corresponding SD. In contrast, PVP-based tablets disintegrated slowly with gradual dissolution. This can be attributed to the binding effect of PVP. The study developed fast disintegrating tablet for intra-oral administration. PMID:23841582

El Maghraby, Gamal M; Elsergany, Ramy N

2014-09-01

16

Kollidon SR colloidal particles as vehicles for oral morphine delivery in pain treatment.  

PubMed

Due to the great importance of new therapeutic routes for morphine in pain treatment, several investigations are under development. In this way, the design of a liquid system for the oral administration of morphine would be of great help, especially in patients with difficulties in swallowing (children and elderly people). The systems studied in this work are kollidon SR microparticles, a biodegradable polymer classically used as excipient in the design of solid dosage forms, as vehicles for morphine. A detailed investigation of the capabilities of the polymer particles to load this drug at their surface is described. Electrophoretic mobility and optical absorbance determinations were used with this aim. The main factors determining the drug incorporation, after incubation of the microparticles in the morphine solutions, were the adsorption time, the type of electrolyte and its concentration, and the drug concentration. The optimum loading conditions were used to perform morphine release evaluations, finding that the release profiles were biphasic since the drug adsorbed was slowly released during 24h after an initial burst release phase. PMID:19167868

Arias, José L; Gómez-Gallo, Amparo; Delgado, Angel V; Ruiz, Ma Adolfina

2009-05-01

17

Stability of benzocaine formulated in commercial oral disintegrating tablet platforms.  

PubMed

Pharmaceutical excipients contain reactive groups and impurities due to manufacturing processes that can cause decomposition of active drug compounds. The aim of this investigation was to determine if commercially available oral disintegrating tablet (ODT) platforms induce active pharmaceutical ingredient (API) degradation. Benzocaine was selected as the model API due to known degradation through ester and primary amino groups. Benzocaine was either compressed at a constant pressure, 20 kN, or at pressure necessary to produce a set hardness, i.e., where a series of tablets were produced at different compression forces until an average hardness of approximately 100 N was achieved. Tablets were then stored for 6 months under International Conference on Harmonization recommended conditions, 25°C and 60% relative humidity (RH), or under accelerated conditions, 40°C and 75% RH. Benzocaine degradation was monitored by liquid chromatography-mass spectrometry. Regardless of the ODT platform, no degradation of benzocaine was observed in tablets that were kept for 6 months at 25°C and 60% RH. After storage for 30 days under accelerated conditions, benzocaine degradation was observed in a single platform. Qualitative differences in ODT platform behavior were observed in physical appearance of the tablets after storage under different temperature and humidity conditions. PMID:23990120

Köllmer, Melanie; Popescu, Carmen; Manda, Prashanth; Zhou, Leon; Gemeinhart, Richard A

2013-12-01

18

Formulation and optimization of orally disintegrating tablets of sumatriptan succinate.  

PubMed

The aims of the present research were to mask the intensely bitter taste of sumatriptan succinate and to formulate orally disintegrating tablets (ODTs) of the taste masked drug. Taste masking was performed by coating sumatriptan succinate with Eudragit EPO using spray drying technique. The resultant microspheres were evaluated for thermal analysis, yield, particle size, entrapment efficiency and in vitro taste masking. The tablets were formulated by mixing the taste masked microspheres with different types and concentrations of superdisintegrants and compressed using direct compression method followed by sublimation technique. The prepared tablets were evaluated for weight variation, thickness, hardness, friability, drug content, water content, in vitro disintegration time and in vitro drug release. All the tablet formulations disintegrated in vitro within 37-410 s. The optimized formulation containing 5% Kollidon CL-SF released more than 90% of the drug within 15 min and the release was comparable to that of commercial product (Suminat®). In human volunteers, the optimized formulation was found to have a pleasant taste and mouth feel and disintegrated in the oral cavity within 41 s. The optimized formulation was found to be stable and bioequivalent with Suminat®. PMID:21804234

Sheshala, Ravi; Khan, Nurzalina; Darwis, Yusrida

2011-01-01

19

Randomised trial of oral morphine for chronic non-cancer pain  

Microsoft Academic Search

SummaryBackground The use of opioid analgesics for chronic non-cancer pain is controversial. Some surveys report good pain relief and improvement in performance while others suggest a poor outcome with a propensity to psychological dependence or addiction.Methods We undertook a randomised double-blind crossover study to test the hypothesis that oral morphine relieves pain and improves the quality of life in patients

D. E Moulin; R Amireh; W. K. J Sharpe; D Boyd; H Merskey; A Iezzi

1996-01-01

20

Oral suspensions of morphine hydrochloride for controlled release: rheological properties and drug release.  

PubMed

Recent developments in pharmaceutical technology have facilitated the design and production of modified release formulas for drugs whose physical, chemical or biological properties impede release and thus might compromise their efficacy or safety. One such drug is morphine, whose short half-life requires repeated doses at short intervals. The use of biocompatible polymers such as ethylcellulose has made it possible to develop microencapsulated formulations which facilitate liquid, sustained-release pharmaceutical formulas for oral administration. We developed a stable final formulation of morphine with an acceptable release profile by comparing the rheological properties and stability of formulations with different thickeners (xanthan gum, Carbopol, and carboxymethylcellulose with microcrystalline cellulose) at different concentrations from 0.25% to 1.0%. Release assays in a Franz-type cell were done to determine the most suitable release profile for the formulation. PMID:21271730

Morales, M E; López, G; Gallardo, V; Ruiz, M A

2011-04-01

21

Effects of Oral Morphine on the Larvae, Pupae and Imago Development in Drosophila Melanogaster  

PubMed Central

Objective: Previous studies, focusing on the effects of abused drugs, have used mice or rats as the main animal models; the present study tries to introduce a simple animal model. For this propose, we investigated the effects of oral morphine consumption by parents on the development of larvae, pupae and imago in Drosophila Melanogaster (D. Melanogaster). Materials and Methods: In this experimental study, twenty male and 20 female D. Melanogaster pupae were housed in test tubes with banana (5 pupae /tube).). Male and female groups each were divided into three experimental group and one control group, which were maintained at 25?. Morphine (0.2, 0.02, 0.002 mg/ml) was added into the test tubes of the experimental groups. The control group maintained at morphine-free test tube. The male and female groups with the same treatment were coupled and then female fertilization, egg deposit, larval, pupae and imago stages were studied macro and microscopically. The SPSS software (version 9.01) was used for statistical evaluations. Results: In the experimental groups, in the larvae stage, both increase and decrease of length and surface area in the pupae stage were observed. The number of larvae pupae, and imago was reduced in the experimental groups. Conclusion: The study showed that oral morphine consumption by parents may affect the development of larvae, pupation and imago stages in D. Melanogaster. The results also showed that D. Melanogaster may be a reliable animal model to study on the concerns about abused drugs especially those with opioids. PMID:23508520

Tekieh, Elaheh; Kazemi, Masoomeh; Dehghani, Leila; Bahramyian, Sina; Sadogi, Mehrangiz; Zardooz, Homeira; Fakhanik-Babaei, Javad; Sahraei, Hedayat

2011-01-01

22

Formulation of multiparticulate systems as lyophilised orally disintegrating tablets.  

PubMed

The current study aimed to exploit the electrostatic associative interaction between carrageenan and gelatin to optimise a formulation of lyophilised orally disintegrating tablets (ODTs) suitable for multiparticulate delivery. A central composite face centred (CCF) design was applied to study the influence of formulation variables (gelatin, carrageenan and alanine concentrations) on the crucial responses of the formulation (disintegration time, hardness, viscosity and pH). The disintegration time and viscosity were controlled by the associative interaction between gelatin and carrageenan upon hydration which forms a strong complex that increases the viscosity of the stock solution and forms tablet with higher resistant to disintegration in aqueous medium. Therefore, the levels of carrageenan, gelatin and their interaction in the formulation were the significant factors. In terms of hardness, increasing gelatin and alanine concentration was the most effective way to improve tablet hardness. Accordingly, optimum concentrations of these excipients were needed to find the best balance that fulfilled all formulation requirements. The revised model showed high degree of predictability and optimisation reliability and therefore was successful in developing an ODT formulation with optimised properties that were able deliver enteric coated multiparticulates of omeprazole without compromising their functionality. PMID:21693189

Alhusban, Farhan; Perrie, Yvonne; Mohammed, Afzal R

2011-11-01

23

Development and evaluation of orally disintegrating tablets (ODTs) containing Ibuprofen granules prepared by hot melt extrusion  

Microsoft Academic Search

In the current study Ibuprofen was embedded in a methacrylate copolymer (Eudragit® EPO) matrix to produce solid dispersions by hot-melt extrusion (HME) processing. The obtained granules were incorporated in orally disintegrating tablets (ODTs). The tablets were developed by varying the ratio of superdisintegrants such as sodium croscarmellose and crosslinked polyvinylpyrrolidone grades while a direct compression process was used to compress

Andreas Gryczke; Silke Schminke; Mohammed Maniruzzaman; Julien Beck; Dennis Douroumis

2011-01-01

24

Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl citrate (OTFC ®) and morphine sulfate immediate release (MSIR ®)  

Microsoft Academic Search

Oral transmucosal fentanyl citrate (OTFC®; Actiq®) is a drug delivery formulation used for management of breakthrough cancer pain. Previous studies with open-label comparisons indicated OTFC was more effective than patients’ usual opioid for breakthrough pain. The objective of this study was to compare OTFC and morphine sulfate immediate release (MSIR®) for management of breakthrough pain in patients receiving a fixed

Paul H Coluzzi; Lee Schwartzberg; John D Conroy; Steve Charapata; Mason Gay; Michael A Busch; Jana Chavez; Jeri Ashley; Dixie Lebo; Maureen McCracken; Russell K Portenoy

2001-01-01

25

Evaluation of coprocessed disintegrants produced from tapioca starch and mannitol in orally disintegrating paracetamol tablet.  

PubMed

The study evaluated two novel coprocessed excipients (with two methods) as disintegrants in an orally disintegrating paracetamol tablet formulation. The tablets produced were assessed for mechanical properties with the use of friability and tensile strength while the release properties were assessed with wetting time, water absorption ratio, disintegration time and dissolution profile. The results obtained showed that the methods of coprocessing and disintegrant incorporation influenced the activities of the disintegrants. The novel disintegrant enhanced the mechanical properties of the tablets containing them as shown by lower friability and higher tensile strength of the tablets. The result further showed that the rate and amount of water absorbed, type of disintegrant and the method of disintegrant incorporation influenced the total amount of paracetamol released. The study concluded that the novel disintegrants will be effective in the formulation of orally disintegrating paracetamol tablets. PMID:25362809

Adeoye, Oluwatomide; Alebiowu, Gbenga

2014-01-01

26

Proniosomal Oral Tablets for Controlled Delivery and Enhanced Pharmacokinetic Properties of Acemetacin.  

PubMed

Free-flowing proniosomal powders of acemetacin (AC) were prepared using the slurry method and maltodextrin as carrier. Positively charged proniosomes composed of 70:20:10 of Span 60/cholesterol (Chol)/stearylamine (SA), respectively, were successively compressed into tablets using direct compression method. The tablets were characterized for weight variability, friability, hardness, drug content uniformity, and dissolution properties. The in vivo evaluation of the prepared proniosomes (powder or tablet forms) after oral administration was investigated by the determination of AC and its active metabolite indomethacin (IND) in the blood of albino rabbits. Results indicated that the increase of Chol from 10% to 20% markedly reduced the efflux of the drug. Further Chol addition from 30% to 50% led to increased AC release rates. The proniosome tablets of AC showed greater hardness and disintegration time and less friability than AC plain tablets. The dissolution of proniosomal tablets indicated a lower drug release percentage compared to powdered proniosomes and AC plain tablets. The mean pharmacokinetic parameters of AC and IND from different formulations indicated increased t 1/2 and area under the curve (AUC) of both AC and IND for proniosomal tablets compared with both proniosomal powders and AC plain tablets. This study suggested the formulation of AC proniosomal powder into tablets to control and extend its pharmacologic effects. PMID:25319057

Shehata, Tamer M; Abdallah, Marwa H; Ibrahim, Mahmoud Mokhtar

2014-10-16

27

[Effect and side effects of oral morphine, lormetazepam and placebos as premedication].  

PubMed

In 60 patients undergoing a curettage in thiopentone induced inhalation anaesthesia with enflurane and N2O/O2 = 2:1, the effects of oral premedication (2 h before anaesthesia) with 30 mg morphine (MST 30) (n = 21), 1 mg lormetazepam (Noctamid) (n = 19) and placebo (n = 21) on psychological (anxiety, depression and asthenia), physiological (blood pressure, heart and respiratory rate) and pain parameters (visual analogue scale, analgesic consumption) were investigated. The study design was single blind, randomized. Before premedication the three groups did not differ in one parameter and so were comparable. MST 30 had a significantly better anxiolytic, Lormetazepam a significantly better antidepressive effect than the compared substance. There were no differences in blood pressure and heart rate. In contrast to lormetazepam and placebo after MST 30 there was no increase in the respiratory rate which can be explained by the anxiolytic stress reducing effect. There was no difference in peri- and intraoperative pain parameters, probably due to the type of surgery. Nausea and vomiting occurred more frequently after MST 30, but there was no significance. A higher rate was probably prevented by the application of transdermal scopolamine the day before surgery. The indication of analgesics (opiates) for premedication is discussed taking the controversy into account. The results of this study show that oral morphine (MST 30) has an anxiolytic effect, one of the most important effects a premedication should have. Further studies should investigate in which types of surgery the analgesic effect of MST 30 is peri- and intraoperatively relevant, so that advantages compared to e.g. Flunitrazepam, Midazolam or Lormetazepam in a higher dosage could be expected. PMID:2888417

Tolksdorf, W; Krug, C; Hartung, M; Hettenbach, A

1987-06-01

28

Prolonged release (PR) oxycodone & naloxone (TarginactTM) fixed combination oral tablets for severe chronic pain  

Microsoft Academic Search

Summary • A fixed dose oral prolonged release (PR) oxycodone and prolonged release (PR) naloxone combination tablet is a new preparation for the treatment of severe pain which can only be adequately managed by opioid analgesics. • Naloxone has been added to counteract opioid induced constipation. The bioavailability of naloxone after oral ad- ministration is <3% because of first pass

Katie Smith

29

Relative bioavailability in humans for oral tablets and solutions of lormetazepam.  

PubMed

A study was carried out to estimate the relative bioavailability of 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1-methyl-1, 3-dihydro-1H-1,4-benzodiazepine-2-one (lormetazepam, Minias) in humans after administration of oral tablets and solutions. Plasma concentration of the drug was measured by gaschromatography with electron capture detector. Six healthy males were each given both formulations. With the oral solution higher plasma peak concentration and a shorter peak time were observed than with tablets. Also the elimination half-life was shorter with the oral solution, while no difference was found with the AUC. PMID:2869762

Zecca, L; Reina, L; Scaglione, F; Ferrario, P; Pirola, R; Ceccarelli, G; Ciampini, M; Fraschini, F

1985-01-01

30

Oral Disintegration Tablets of Stavudine for HIV Management: A New Technological Approach.  

PubMed

Stavudine oral disintegration tablets were formulated to minimize the bitter taste and to reduce the first-pass hepatic metabolism. The various precompression parameters like the angle of repose, bulk density, compressibility index and Hausner's ratio were determined for the powder blend. In this study, 14 formulations of stavudine oral disintegration tablet were prepared by direct compression method. The tablets were evaluated for weight variation, percentage friability, disintegration time, hardness, wetting time and water absorption ratio. The in vitro dissolution study results of the batch S1 (stavudine+crospovidone+sodium starch glycollate) are encouraging as highest dissolution rate (99.2% in 100 min) and lowest time of disintegration (56 s) was achieved. The in vivo drug release studies were carried out in rabbits and the relative bioavailability of formulation S1 was found to be 2.83 times greater than that of conventional tablets. PMID:23798782

Sankar, V; Ramakrishna, B; Devi, P Shalini; Karthik, S

2012-11-01

31

Sugar End-Capped Poly d , l -lactides as Excipients in Oral Sustained Release Tablets  

Microsoft Academic Search

Sugar end-capped poly-d,l-lactide (SPDLA) polymers were investigated as a potential release controlling excipient in oral sustained release matrix\\u000a tablets. The SPDLA polymers were obtained by a catalytic ring-opening polymerization technique using methyl ?-d-gluco-pyranoside as a multifunctional initiator in the polymerization. Polymers of different molecular weights were synthesized\\u000a by varying molar ratios of monomer\\/catalyst. The matrix tablets were prepared by direct

Sirpa Vuorinen; Jyrki Heinämäki; Osmo Antikainen; Mohammed Lahcini; Timo Repo; Jouko Yliruusi

2009-01-01

32

Stability of cilazapril in pediatric oral suspensions prepared from commercially available tablet dosage forms.  

PubMed

Abstract: Cilazapril is a drug commonly used in management of heart failure in pediatric population. On pharmaceutical market it is available only in inconvenient for pediatric use tablet dosage forms. Until now, no oral liquid formulation containing cilazapril has been evaluated. Therefore, the aim of this study was to prepare easy to made and palatable 1 mg/mL oral liquid formulation with cilazapril (with consideration of original and generic cilazapril tablet and different packages) and subsequent investigation of physicochemical stability of these suspensions. Formulations were compounded using cilazapril obtained from original or generic cilazapril marketed tablet formulations and Ora-Blend" suspending agent. Stability of prepared suspensions stored in closed amber glass or amber plastic PET bottles in the temperature of 298 K was estimated throughout 28 day shelf-life period. Chemical stability was assessed by HPLC cilazapril stability indicating method. Physical stability was evaluated by appearance, taste, smell, pH and theological assessments. Cilazapril oral suspensions at concentration of 1 mg/mL demonstrated satisfactory stability over 28 day long storage at room temperature. Cilazapril concentrations remained within acceptable limit (+/- 10%) stored in closed amber bottles made of glass or PET material. Moreover, suspensions physical properties remained unaffected. Cilazapril - Ora-Blend* pediatric oral liquid is easy to made, palatable and stable when stored at room temperature for 28 days. Stability of cilazapril oral liquid remains unchanged while using cilazapril tablets produced by different manufacturers and bottles made of amber glass or PET material. PMID:25272892

Stanisz, Beata J; Paszun, Sylwia K; Zalewska, Anna

2014-01-01

33

The analgesic effect of oral delta-9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions  

Microsoft Academic Search

From folk medicine and anecdotal reports it is known that Cannabis may reduce pain. In animal studies it has been shown that delta-9-tetrahydrocannabinol (THC) has antinociceptive effects or potentiates the antinociceptive effect of morphine. The aim of this study was to measure the analgesic effect of THC, morphine, and a THC-morphine combination (THC-morphine) in humans using experimental pain models. THC

Myrtha Naef; Michele Curatolo; Steen Petersen-Felix; Lars Arendt-Nielsen; Alex Zbinden; Rudolf Brenneisen

2003-01-01

34

Formulation and Characterization of Oral Mucoadhesive Chlorhexidine Tablets Using Cordia myxa Mucilage  

PubMed Central

Background The dilution and rapid elimination of topically applied drugs due to the flushing action of saliva is a major difficulty in the effort to eradicate infections of oral cavity. Utilization a proper delivery system for incorporation of drugs has a major impact on drug delivery and such a system should be formulated for prolonged drug retention in oral cavity. Objectives The aim of the present study was the use of mucilage of Cordia myxa as a mucoadhesive material in production of chlorhexidine buccal tablets and its substitution for synthetic polymers such as HPMC. Materials and Methods The influence of mucilage concentration on the physicochemical responses (hardness, friability, disintegration time, dissolution, swelling, and muco-adhesiveness strength) was studied and swelling of mucilage and HPMC were compared. The evaluated responses included pharmacopoeial characteristics of tablets, the force needed to separate tablets from mucosa, and the amount of water absorbed by tablets. Results In comparison to HPMC, the rise of mucilage concentration in the formulations increased disintegration time, drug dissolution rate, and reduced MDT. Also, compared to 30% HPMC, muco-adhesiveness strength of buccal tablets containing 20% mucilage was significantly higher. Conclusions It can be concluded that the presence of Cordia myxa powdered mucilage may significantly affect the tablet characteristics, and increasing in muco-adhesiveness may be achieved by using 20% w/w mucilage. PMID:24624170

Moghimipour, Eskandar; Aghel, Nasrin; Adelpour, Akram

2012-01-01

35

The Relative Potency of Oral Transmucosal Fentanyl Citrate Compared with Intravenous Morphine in the Treatment of Moderate to Severe Postoperative Pain  

Microsoft Academic Search

Pharmacokinetic studies have shown that oral trans- mucosal absorption of fentanyl is relatively rapid com- pared with gastrointestinal absorption, and it results in increased bioavailability. We designed this study to es- tablish the relative potency of oral transmucosal fenta- nyl citrate (OTFC) compared with IV morphine in 133 postoperative patients. The morning after surgery, pa- tients randomly received one dose

J. Lance Lichtor; Ferne B. Sevarino; Girish P. Joshi; Michael A. Busch; Earl Nordbrock; Brian Ginsberg

1999-01-01

36

Taste Masking of Lornoxicam by polymer carrier system and formulation of oral disintegrating tablets  

Microsoft Academic Search

Lornoxicam is a non steroidal anti-inflammatory drug with analgesic properties and belongs to the class oxicams. It is extremely bitter in taste. The purpose of this research was to develop a bitterless oral disintegrating tablet of Lornoxicam. Taste masking was done by complexing Lornoxicam with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratios. In vitro release profile obtained at pH

Rajesh S. Jadon; Swadesh Nayak; Sabita Amlan; Vikas Deep Vaidya; Prashant Khemariya; Sandip Sumbhate

2009-01-01

37

The bioavailability of cefpodoxime proxetil tablets relative to an oral solution.  

PubMed

The bioavailability of cefpodoxime proxetil tablets relative to an oral solution of cefpodoxime proxetil in a sucrose/alcohol/citric acid vehicle was studied in 11 healthy volunteers in a randomized, crossover study. Fasted subjects took one cefpodoxime proxetil 100 mg tablet or 50 mL of a 2 mg mL-1 cefpodoxime proxetil oral solution on two separate occasions. In a third study period, all subjects took a 100 mg dose of the oral solution with a high-fat meal to investigate the effect of food on cefpodoxime proxetil absorption from the oral solution. Serial blood samples were obtained over a 24 h period, and urine was collected for 48 h after dosing. Cefpodoxime concentrations in plasma and in urine were determined using HPLC methods. The bioavailability of cefpodoxime proxetil tablets relative to the oral solution was 82%, as determined from AUC ratios. There was no difference in the rate of cefpodoxime absorption between dosage forms. Food had no effect on the extent of drug absorption from the oral solution but did result in delayed absorption. These results suggest that complete dissolution of cefpodoxime proxetil is critical for optimal bioavailability. PMID:7548778

Borin, M T; Forbes, K K; Hughes, G S

1995-05-01

38

Mental Symptoms and Drug Use in Maintenance Treatment with Slow-Release Oral Morphine Compared to Methadone: Results of a Randomized Crossover Study.  

PubMed

Background: Opioid maintenance treatment is the option of choice to stabilize opioid-dependent patients. Whilst efficacy of methadone and buprenorphine has been studied extensively, fewer data on slow-release oral morphine are available. Aims: This study analyzes the effects of slow-release oral morphine compared to methadone with regard to self-reported mental symptoms, drug use and satisfaction with treatment. Methods: The study was carried out as an open-label randomized crossover trial in 14 treatment sites in Switzerland and Germany. It comprised 2 crossover periods of 11 weeks each. For measuring mental symptoms, the Symptom Checklist-27 (SCL-27) was used. Drug and alcohol use was assessed by the number of consumption days, and treatment satisfaction by a visual analogue scale. Results: A total of 157 patients were included for the analyses (per-protocol sample). Statistically significantly better outcomes for morphine as compared to methadone treatment were found for overall severity of mental symptoms (SCL-27 Global Severity Index), as well as 5 of the 6 syndrome groups of the SCL-27, and for treatment satisfaction. There were no statistically significant differences with regard to drug or alcohol use between groups. Conclusions: This study supports positive effects of slow-release oral morphine compared to methadone on patient-reported outcomes such as mental symptoms and treatment satisfaction with comparable effects on concomitant drug use. Slow-release oral morphine represents a meaningful alternative to methadone for treatment of opioid dependence. © 2014 S. Karger AG, Basel. PMID:25427944

Verthein, Uwe; Beck, Thilo; Haasen, Christian; Reimer, Jens

2014-11-22

39

Orally Administered Nano-curcumin to Attenuate Morphine Tolerance: Comparison between Negatively Charged PLGA and Partially and Fully PEGylated Nanoparticles  

PubMed Central

We have formulated hydrophobic curcurmin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] into stable nanoparticle suspensions (nano-curcumin) to overcome its relatively low bioavailability, high rate of metabolism and rapid elimination and clearance from the body. Employing the curcumin nanoformulations as the platform, we discovered that curcumin has the potential to alleviate morphine tolerance. The two types of stable polymeric nanoparticles - poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) - and the hybrid of the two were generated using flash nanoprecipitation integrated with spray drying. The optimized formulations have high drug loading (>45%), small particles size with narrow distribution, and controlled surface properties. Mice behavioral studies (tail-flick and hot-plate tests) were conducted to verify the effects of nano-curcumin on attenuating morphine tolerance. Significant analgesia was observed in mice during both tail-flick and hot-plate tests using orally administrated nano-curcumin following subcutaneous injections of morphine. However, unformulated curcumin at the same dose showed no effect. Compared with PEGylated nano-curcumin, negatively charged PLGA nanoparticles showed better functionality. PMID:24195658

Shen, Hao; Hu, Xiaoyu; Szymusiak, Magdalena; Wang, Zaijie Jim; Liu, Ying

2014-01-01

40

Orally administered nanocurcumin to attenuate morphine tolerance: comparison between negatively charged PLGA and partially and fully PEGylated nanoparticles.  

PubMed

We have formulated hydrophobic curcurmin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] into stable nanoparticle suspensions (nanocurcumin) to overcome its relatively low bioavailability, high rate of metabolism, and rapid elimination and clearance from the body. Employing the curcumin nanoformulations as the platform, we discovered that curcumin has the potential to alleviate morphine tolerance. The two types of stable polymeric nanoparticles, poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA), and the hybrid of the two were generated using flash nanoprecipitation integrated with spray drying. The optimized formulations have high drug loading (>45%), small particles size with narrow distribution, and controlled surface properties. Mice behavioral studies (tail-flick and hot-plate tests) were conducted to verify the effects of nanocurcumin on attenuating morphine tolerance. Significant analgesia was observed in mice during both tail-flick and hot-plate tests using orally administered nanocurcumin following subcutaneous injections of morphine. However, unformulated curcumin at the same dose showed no effect. Compared with PEGylated nanocurcumin, negatively charged PLGA nanoparticles showed better functionality. PMID:24195658

Shen, Hao; Hu, Xiaoyu; Szymusiak, Magdalena; Wang, Zaijie Jim; Liu, Ying

2013-12-01

41

Design and evaluation of microwave-treated orally disintegrating tablets containing polymeric disintegrant and mannitol.  

PubMed

Microwave (MW) treatment was used to develop a formulation process for the preparation of wet molded orally disintegrating tablets (ODTs) consisting of mannitol and polymeric disintegrant with improved hardness and disintegration properties. The wet molded tablets were prepared in accordance with the conventional methods and subsequently heated by MW irradiation to induce the swelling of the tablet. Croscarmellose sodium, crospovidone, and low-substituted hydroxypropylcellulose (L-HPC) were evaluated for their use with this technology. NBD-020, which is a grade of L-HPC, provided the better hardness and disintegration results. In addition, the crystalline forms of mannitol impacted on hardness and disintegration properties of the ODT upon MW irradiation. The effects of the disintegrant ratio, ? and ? crystalline mannitol ratio, amount of water, and compression force on the ODT properties were evaluated using the design of experiment method. MW-induced swelling was enhanced by an increase in the disintegrant ratio. Although the hardness of the tablet increased following MW treatment, the disintegration time became less than that of the MW-untreated tablets as the ?-mannitol ratios increased. Taken together, the results indicated that the polymeric disintegrant greatly improved the properties of the molded tablets in combination with MW treatment. PMID:23524122

Sano, Syusuke; Iwao, Yasunori; Noguchi, Shuji; Kimura, Susumu; Itai, Shigeru

2013-05-01

42

The Role of Oral Controlled Release Matrix Tablets in Drug Delivery Systems  

PubMed Central

Formulations that are able to control the release of drug have become an integral part of the pharmaceutical industry. In particular oral drug delivery has been the focus of pharmaceutical research for many years. This type of drug delivery has been at the centre of research due to its many benefits over conventional dosage. The focus of this review is on matrix tablets due to their widely use and simplicity of the formulation. This includes the discussion of various types of matrix tablets and factors affecting the drug release from these formulations. The mechanism of drug release from HPMC matrices is also discussed. PMID:23678458

Nokhodchi, Ali; Raja, Shaista; Patel, Pryia; Asare-Addo, Kofi

2012-01-01

43

Formulation and evaluation of clozapine orally disintegrating tablets prepared by direct compression.  

PubMed

In this study, clozapine orally disintegrating tablets (ODTs) were prepared by direct compression method. Disintegration time, resistance to crushing of tablets, porosity, friability, dissolution tests were performed and dissolution profiles of ODTs were investigated. Morphological and interaction studies were also performed. Friability values were found to be less than 1%. All tablet formulations disintegrated within 1 min and fulfilled the 3 min disintegration time required for ODTs given in the European Pharmacopoeia. More than 85% of the labeled amount of clozapine was dissolved in 15 min from the ODTs. No interaction or changes were found between active substance and excipients. As a result of the studies, ODT formulations developed in this study can be suggested as promising formulations, which assist development and manufacturing a generic product of clozapine. PMID:23469682

Olmez, S S; Vural, I; Sahin, S; Ertugrul, A; Capan, Y

2013-02-01

44

Development and optimization of buspirone oral osmotic pump tablet  

PubMed Central

The aim of the current study was to design a porous osmotic pump–based drug delivery system for controlling the release of buspirone from the delivery system. The osmotic pump was successfully developed using symmetric membrane coating. The core of the tablets was prepared by direct compression technique and coated using dip-coating technique. Drug release from the osmotic system was studied using USP paddle type apparatus. The effect of various processing variables such as the amount of osmotic agent, the amount of swellable polymer, concentration of the core former, concentration of the plasticizer, membrane thickness, quantum of orifice on drug release from osmotic pump were evaluated. Different kinetic models (zero order, first order and Higuchi model) were applied to drug release data in order to establish the kinetics of drug release. It was found that the drug release was mostly affected by the amount of NaCl as osmotic agent, the swellable polymer; hydroxy propyl methyl cellulose (HPMC), the amount of PEG-400 and cellulose acetate in the coating solution and thickness of the semipermeable membrane. The optimized formulation released buspirone independent of pH and orifice quantum at the osmogen amount of 42%, hydrophilic polymer of 13% and pore size of 0.8 mm on the tablet surface. The drug release of osmotic formulation during 24 h showed zero order kinetics and could be suggested that this formulation as a once-daily regimen improves pharmacokinetic parameters of the drug and enhances patient compliance.

Derakhshandeh, K.; berenji, M. Ghasemnejad

2014-01-01

45

Preparation and evaluation of taste-masked dextromethorphan oral disintegrating tablet.  

PubMed

This study was aimed at preparing and evaluating oral disintegrating tablets (ODTs) using a strongly cationic resin, Amberlite(®) IRP-69, to mask the bitter taste of a delivered drug, i..e. dextromethorphan hydrobromide. The drug was loaded into the resin (referred to as resinate) or physically mixed with the resin (referred to as physical mixture), and was then incorporated into ODTs by direct compression. A variety of formulae was developed to acquire the optimal formulations of taste-masked ODTs that had acceptable hardness and mouth feel (grittiness). The optimized ODTs were further evaluated for thickness, diameter, weight, friability, disintegration time, wetting time, wetting rate, drug content, drug release and degree of bitter taste, respectively. The thickness, diameter, weight and friability of the tablet with resinate were slightly higher than those with physical mixture. The tablet with resinate had a longer disintegration time, corresponding with its slower wetting time and rate. Both tablets with resinate and physical mixture provided a sustained pattern of drug release. However, only tablets with resinate successfully masked the bitter taste of the drug. In conclusion, the combination of drug and ion exchange resin as resinate could increase the palatability and acceptability of ODTs containing bitter drugs. PMID:21142821

Samprasit, Wipada; Opanasopit, Praneet; Akkaramongkolporn, Prasert; Ngawhirunpat, Tanasait; Wongsermsin, Kaewnapa; Panomsuk, Suwannee

2012-01-01

46

Tableting lipid-based formulations for oral drug delivery: a case study with silica nanoparticle-lipid-mannitol hybrid microparticles.  

PubMed

Silica-lipid-mannitol hybrid (SLMH) microparticles have been developed that were compressible into high quality tablets suitable for oral dosing and delivery of poorly soluble drugs. SLMH tablets enable high lipid-loading levels (>40%) and retain the immediate release, enhanced lipase digestion and drug solubilisation performance. Specifically, we report formulation optimisation of SLMH microparticles and tablets using coumarin 102 (log P = 4.09) as a model Biopharmaceutics Classification System class II drug. SLMH tablets were acceptable according to standard British Pharmacopoeia friability, hardness and disintegration tests; this is not the case for conventional dry emulsions. Furthermore, in vitro dissolution and pancreatic-lipase-induced lipolysis studies under simulated intestinal conditions have demonstrated enzymatic-digestion-mediated drug solubilisation. SLMH microparticles and tablets are suitable as liquid lipid containing solid dosage forms for enhancing and controlling oral absorption of poorly soluble drugs. PMID:23242712

Bremmell, Kristen E; Tan, Angel; Martin, Amanda; Prestidge, Clive A

2013-02-01

47

Development and Evaluation of Cetirizine HCl Taste-Masked Oral Disintegrating Tablets  

Microsoft Academic Search

The purpose of the current study was to mask the taste of cetirizine HCl and to incorporate the granules produced in oral\\u000a disintegrating tablets (ODT). The bitter, active substance was coated by fluidized bed coating using Eudragit® RL30-D at levels\\u000a between 15% and 40% w\\/w. The ODTs were developed by varying the ratio of superdisintegrants such as sodium croscarmellose, crospovidone

Dionysios Dennis Douroumis; Andreas Gryczke; Silke Schminke

2011-01-01

48

Meloxicam taste-masked oral disintegrating tablet with dissolution enhanced by ion exchange resins and cyclodextrin.  

PubMed

The purpose of this study was to develop taste-masked oral disintegrating tablets (ODTs) using the combination of ion exchange resin and cyclodextrin, to mask the bitter taste and enhance drug dissolution. Meloxicam (MX) was selected as a model drug with poor water solubility and a bitter taste. Formulations containing various forms of MX (free drug, MX-loaded resin or resinate, complexes of MX and 2-hydroxypropyl-?-cyclodextrin (HP?CD) or MX/HP?CD complexes, and a mixture of resinate and MX/HP?CD complexes) were made and tablets were prepared by direct compression. The ODTs were evaluated for weight variation, thickness, diameter, hardness, friability, disintegration time, wetting time, MX content, MX release, degree of bitter taste, and stability. The results showed that thickness, diameter, weight, and friability did not differ significantly for all of these formulations. The tablet hardness was approximately 3 kg/in.(2), and the friability was less than 1%. Tablets formulated with resinate and the mixture of resinate and MX/HP?CD complexes disintegrated rapidly within 60 s, which is the acceptable limit for ODTs. These results corresponded to the in vivo disintegration and wetting times. However, only tablets containing the mixture of resinate and MX/HP?CD complexes provided complete MX dissolution and successfully masked the bitter taste of MX. In addition, this tablet was stable at least 6 months. The results from this study suggest that the appropriate combination of ion exchange resin and cyclodextrin could be used in ODTs to mask the bitter taste of drug and enhance the dissolution of drugs that are weakly soluble in water. PMID:23835739

Samprasit, Wipada; Akkaramongkolporn, Prasert; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Opanasopit, Praneet

2013-09-01

49

Selection of generic preparations of famotidine orally disintegrating tablets for use in unit-dose packages.  

PubMed

Changes in the hardness, dissolution, and the disintegration time of brand name and generic preparations (6 preparations) of famotidine orally disintegrating tablets were investigated. Tablets had been stored in a thermo-hygrostat-controlled environment set to simulate the home conditions of patients up to 8 weeks after unit-dose packaging. Among the tablets in unit-dose packaging prepared immediately after blister packs (BP) were opened, one generic had decreased hardness to less than 2.0 kg after 1 week, 55.1% of its initial hardness value, and a shorter disintegration time of about 1/5 of its initial disintegration time. Generics met the standard for dissolution 8 weeks after unit-dose packaging. The decrease in hardness after unit-dose packaging is presumed to be associated with additives, and particularly the types and amounts of binding agents, but evidence of this association was lacking. The hardness noted in drug interview forms (IFs) and the state of sales of bulk tablet packages must be determined to facilitate the selection of generics that remain hard even after unit-dose packaging. PMID:23229147

Yamazaki, N; Iizuka, R; Miyazawa, S; Wada, Y; Shimokawa, K; Ishii, F

2012-10-01

50

Impact of active ingredients on the swelling properties of orally disintegrating tablets prepared by microwave treatment.  

PubMed

The impact of different active pharmaceutical ingredients (APIs) loading on the properties of orally disintegrating tablets (ODTs) prepared according to our previously reported microwave (MW) treatment process was evaluated using famotidine (FAM), acetaminophen (AAP), and ibuprofen (IBU). None of the APIs interrupted the tablet swelling during the MW treatment and the tablet hardness were improved by more than 20 N. MW treatment, however, led to a significant increase in the disintegration time of the ODTs containing IBU, but it had no impact on that of the ODTs containing FAM or AAP. This increased disintegration time of the ODTs containing IBU was attributed to the relatively low melting point of IBU (Tm=76 °C), with the IBU particles melting during the MW treatment to form agglomerates, which interrupted the penetration of water into the tablets and delayed their disintegration. The effects of the MW treatment on the chemical stability and dissolution properties of ODTs were also evaluated. The results revealed that MW treatment did not promote the degradations of FAM and AAP or delay their release from the ODTs, while dissolution of the ODTs containing IBU delayed by MW treatment. Based on these results, the MW method would be applicable to the preparation of ODTs containing APIs with melting points higher than 110 °C. PMID:24709215

Sano, Syusuke; Iwao, Yasunori; Kimura, Susumu; Noguchi, Shuji; Itai, Shigeru

2014-07-01

51

Orally disintegrating tablet of novel salt of antiepileptic drug: formulation strategy and evaluation.  

PubMed

The aim of present research was to design and evaluate orally disintegrating tablet (ODT) of novel lamotrigine-cyclamate salt. Box-Behnken response surface methodology was selected to design the optimized formulation. The independent factors selected were tablet hardness (X1), disintegrant (X2) and lubricant (X3) levels, and responses chosen were disintegration time (DT, Y1), friability (Y2), T50 (Y3), and T90 (Y4). The tablets were also characterized for drug uniformity by near infrared chemical imaging (NIR-CI) and taste masking evaluation by electronic tongue. All the selected independent variables were statistically (p<0.05) effect the Y1 while Y2, Y3, and Y4 affected only by X2. The optimized ODT was found to meet the regulatory requirement of DT and friability specification. The NIR-CI images indicated uniform distribution of active and inactive ingredients within the tablets. The electronic tongue results were analyzed by principle component analysis (PCA). It indicated that novel salt of lamotrigine and its ODT formulation have a taste similar to cyclamic acid which is indicated by close proximity on PCA score plot, lower Euclidean distance, and high discrimination index values. Furthermore, these parameters were very close to ODT placebo formulation. On the other hand, lamotrigine, its ODT, and placebo formulation were far from each other. In summary, lamotrigine salt provides another avenue for pediatric friendly formulation for children and will enhance patience compliance. PMID:23800704

Rahman, Ziyaur; Siddiqui, Akhtar; Khan, Mansoor A

2013-11-01

52

Sufentanil Sublingual Tablet System vs. Intravenous Patient-Controlled Analgesia with Morphine for Postoperative Pain Control: A Randomized, Active-Comparator Trial  

PubMed Central

Background Problems with intravenous patient-controlled analgesia (IV PCA) are well known, including invasive route of delivery and pump programming errors. The primary objective of this study was to evaluate patient satisfaction with a novel sublingual sufentanil PCA system (sufentanil sublingual tablet system 15 mcg with a 20-minute lockout interval; SSTS) to IV PCA morphine sulfate 1 mg with a 6-minute lockout interval (IV PCA MS) for the management of acute postoperative pain. Methods This was a randomized, open-label, 48-hour non-inferiority study with optional extension to 72 hours at 26 U.S. sites enrolling patients scheduled for elective major open abdominal or orthopedic (hip or knee replacement) surgery. The primary outcome measure was the proportion of patients who responded “good” or “excellent” (collectively “success”) at the 48-hour timepoint on the Patient Global Assessment of method of pain control (PGA48). Results A total of 357 patients received study drug and 78.5% vs. 65.6% of patients achieved PGA48 “success” for SSTS vs. IV PCA MS, respectively, demonstrating non-inferiority (P < 0.001 using the one-side Z-test against the non-inferiority margin) as well as statistical superiority for treatment effect (P = 0.007). Patients using SSTS reported more rapid onset of analgesia and patient and nurse ease of care and satisfaction scores were higher than IV PCA MS. Adverse events were similar between the 2 groups; however, SSTS had fewer patients experiencing oxygen desaturations below 95% compared to IV PCA MS (P = 0.028). Conclusions Sufentanil sublingual tablet system is a promising new analgesic technology that may address some of the concerns with IV PCA. PMID:25155134

Melson, Timothy I; Boyer, David L; Minkowitz, Harold S; Turan, Alparslan; Chiang, Yu-Kun; Evashenk, Mark A; Palmer, Pamela P

2014-01-01

53

Formulation design for orally disintegrating tablets containing enteric-coated particles.  

PubMed

The purpose of this study was to investigate the applicability of our newly developed technology (RACTAB® technology) for preparing orally disintegrating tablets (ODTs) containing enteric-coated particles. Tamsulosin hydrochloride (TAM) was used as a model drug contained in the enteric-coated particles. Enteric-coated particles containing TAM (ECP-T) were prepared by spray coating a mixture of TAM with controlled-release materials. ECP-T was then mixed with rapidly disintegrating granules (RDGs), which were prepared using the suspension spray-coating method, and was tableted to form ODTs (ODTRAC). ODTRAC was evaluated for its hardness, thickness, internal structure (X-ray-CT scanning), functional properties (controlled-release profile), and in vivo disintegration time. Since RDGs with micronized ethylcellulose (MEC) increased tablet hardness by increasing the contact frequency between granules, ODTRAC containing ECP-T exhibited high hardness (>50?N) and low friability (<0.5%) with a relatively low compression force. After tableting, the structure of ECP-T in ODTRAC remained intact and no damage was observed on the surface. ECP-T recovered from ODTRAC showed the same dissolution profile of TAM in Japanese Pharmacopoeia (JP) 1st and JP 2nd media as that of intact ECP-T, which indicated that the tableting process did not affect the acid-resistibility of the particle. In addition, ODTRAC rapidly disintegrated in vivo (< 30?s), even at a high compression force (at 9 kN). These findings clearly suggest that RACTAB® technology is a useful approach to prepare ODTs containing enteric-coated particles. PMID:24789923

Okuda, Yutaka; Okamoto, Yasunobu; Irisawa, Yosuke; Okimoto, Kazuto; Osawa, Takashi; Yamashita, Shinji

2014-01-01

54

Evaluating the Effects of Oral Morphine on Embryonic Development of Cerebellum in Wistar Rats  

PubMed Central

In the present research, the effect of morphine consumption during pregnancy on the development of the embryo's spinal cord was studied in Wistar rat. Female Wistar rats (Wt: 250-300 g) were mated with males. The test group received morphine (0.01 mg/ml) in their drinking water. Pregnant rats were later killed with chloroform on the 12th, 13th and 14th days of pregnancy, and the embryos were taken out surgically. The embryos were fixed in formalin 10% for 2 weeks. Then, the weight of fixed embryos was calculated by a scale. In addition, several animals’ sizes including fronto-posterior and lateral length were measured by a caliper. Tissue processing, sectioning and hematoxylin and eosin (H&E) staining were applied for the embryos. The sections were examined for spinal cord development by light microscope and MOTIC software. Significant decrease was observed in the fronto-posterior and lateral length and the weight of the embryos in the test groups. The thickness of the white matter layer decreased on the 12th, 13th and 14th embryonic days. The thickness of the spine's grey layer was also less than the control group, on the same days. Increase in the length of the ependimal duct observed as well. Number of grey substance cells decreased compared to the control group within the same days. Meanwhile, thickness of the germinal layer reduced in comparison to the control group on the mentioned days. In conclusion, morphine consumption during pregnancy causes defects in growth and completion of the spinal cord. PMID:25337339

Niknam, Narges A.; Azarnia, Mahnaz; Bahadoran, Hossein; Kazemi, Masoomeh; Tekieh, Elaheh; Ranjbaran, Mina; Sahraei, Hedayat

2013-01-01

55

Development of orally disintegrating tablets comprising controlled-release multiparticulate beads  

PubMed Central

Melperone is an atypical antipsychotic agent that has shown a wide spectrum of neuroleptic properties, particularly effective in the treatment of senile dementia and Parkinson’s-associated psychosis, and is marketed in Europe as an immediate-release (IR) tablet and syrup. An orally disintegrating tablet (ODT) dosage form would be advantageous for patients who experience difficulty in swallowing large tablets or capsules or those who experience dysphagia. Controlled-release (CR) capsule and ODT formulations containing melperone HCl were developed with target in vitro release profiles suitable for a once-daily dosing regimen. Both dosage forms allow for the convenient production of dose-proportional multiple strengths. Two ODT formulations exhibiting fast and medium release profiles and one medium release profile capsule formulation (each 50?mg) were tested in vivo using IR syrup as the reference. The two medium release formulations were shown to be bioequivalent to each other and are suitable for once-daily dosing. Based on the analytical and organoleptic test results, as well as the blend uniformity and in-process compression data at various compression forces using coated beads produced at one-tenth (1/10) commercial scale, both formulations in the form of CR capsules and CR ODTs have shown suitability for progression into further clinical development. PMID:22356215

2012-01-01

56

Preparation and evaluation of unpleasant taste-masked pioglitazone orally disintegrating tablets.  

PubMed

This study aimed to evaluate the taste and mouth feel of newly designed orally disintegrating tablets (ODTs) of pioglitazone, which is a typical type 2 diabetes medicine with an unpleasant taste, using a visual analog scale (VAS) analysis. The ODTs were subjected to either of these 2 taste-masking procedures: a physical masking procedure that included coating the inactive core granules with mixture of pioglitazone and Eudragit(®) E PO, followed by mixing the granules with aspartame and other excipients to form the tablet (physical masking ODT); or a gustatory masking procedure that involved blending pioglitazone with both sodium chloride and aspartame, followed by mixing the blend with other excipients to form the tablet (gustatory masking ODT). From the results of the VAS analysis, physical masking could suppress the bitterness but not the astringent; therefore, the overall palatability of the ODT was considered not improved. In contrast, gustatory masking significantly suppressed both the bitterness and astringent, and offered a slight sweetness; therefore, the overall palatability of the ODT was considered improved. In conclusion, VAS is a useful tool to evaluate the taste of ODTs and that gustatory masking can effectively mask the unpleasant taste of pioglitazone ODT. PMID:23419665

Nakano, Yoshinori; Maeda, Arisa; Uchida, Shinya; Namiki, Noriyuki

2013-03-25

57

Safety and tolerability of slow-release oral morphine versus methadone in the treatment of opioid dependence.  

PubMed

Opioid substitution treatment (OST) for opioid dependence may be limited by adverse events (AEs). Increasing the range of therapeutic options optimizes outcomes and facilitates patient management. An international, multi-center, two-phase study investigated the efficacy and safety of slow-release oral morphine (SROM) versus methadone in patients receiving methadone therapy for opioid dependence. In phase 1 (two way cross-over, 11 weeks each period) patients were randomized to SROM or methadone oral solution. In phase 2 (25 weeks), patients continued treatment with SROM (group A) or switched from methadone to SROM (group B). In total, 211 out of 276 completed phase 1 and 198 entered phase 2 (n=95 group A, n=103 group B). Treatment with both SROM and methadone was well tolerated. However, the mean QTc-interval associated with methadone was significantly longer than that under SROM. Higher treatment satisfaction, fewer cravings for heroin, and lower mental stress were reported with SROM. This study adds a significant further weight of evidence that SROM is an effective and well tolerated long-term maintenance treatment for opioid dependence with a beneficial risk profile compared to methadone regarding cardiac effects and supports its clinical utility. PMID:25064422

Hämmig, Robert; Köhler, Wilfried; Bonorden-Kleij, Karin; Weber, Bernd; Lebentrau, Karin; Berthel, Toni; Babic-Hohnjec, Lucija; Vollmert, Christian; Höpner, Doris; Gholami, Najibulah; Verthein, Uwe; Haasen, Christian; Reimer, Jens; Ruckes, Christian

2014-10-01

58

Preparation and evaluation of taste-masked donepezil hydrochloride orally disintegrating tablets.  

PubMed

The purpose of this research was to prepare and evaluate a non-bitter donepezil hydrochloride (DH) orally disintegrating tablet (ODT) for enhanced patient compliance. Taste masking was done by preparing microspheres with different ratios of drug and Eudragit EPO using spray drying method. The entrapment of the drug into microspheres was confirmed by scanning electron microscope (SEM) and X-ray powder diffraction. It was found that microspheres with a drug-polymer ratio of 1 : 2 could mask the taste obviously by inhibiting the release of DH in simulated salivary fluid. Microspheres-loaded tablets containing Polyplasdone NF and Low substituted Hydroxypropyl Cellulose (L-HPC) both at a 10% level showed rapid disintegration, in vitro (15.5 s) and in vivo (19.8 s), which were faster than that of marketed tablets (36.7, 41.3 s, respectively). Results from taste evaluation in human volunteers revealed that the ODTs with taste-masked microspheres had significantly enhanced palatability. Dissolution in vitro and pharmacokinetics in rats were evaluated for the tested ODTs compared to the donepezil hydrochloride commercial product (ARICEPT). Both tablets showed comparable dissolution patterns in vitro and similar area under curve from 0 to 24 h (AUC(0-24)), C(max) and T(max) of DH in vivo to each other, suggesting that the tested ODTs might give the similar drug efficacy in rats compared to that of ARICEPT. Thus, it was concluded that DH ODTs with masked taste were obtained by Eudragit EPO-based microspheres, drug loaded microspheres neither decreased the bioavailability nor delayed the release of DH. PMID:20686233

Yan, Yi-Dong; Woo, Jong Soo; Kang, Joon Heok; Yong, Chul Soon; Choi, Han-Gon

2010-01-01

59

A randomised crossover trial of patient controlled intranasal fentanyl and oral morphine for procedural wound care in adult patients with burns  

Microsoft Academic Search

This study sought to compare the analgesic efficacy and safety of patient controlled intra-nasal (PCIN) fentanyl with oral morphine for procedural wound care in burns patients. A randomised double-blind placebo controlled, two period, two-treatment crossover trial was conducted within the Burns Unit of a major teaching hospital in Perth, Western Australia. Patients requiring identical wound care procedures on two consecutive

Judith Finn; Jan Wright; Joy Fong; Eileen Mackenzie; Fiona Wood; Gavin Leslie; Anna Gelavis

2004-01-01

60

Evidence-Based Nanoscopic and Molecular Framework for Excipient Functionality in Compressed Orally Disintegrating Tablets  

PubMed Central

The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2–10 µm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale. PMID:25025427

Al-khattawi, Ali; Alyami, Hamad; Townsend, Bill; Ma, Xianghong; Mohammed, Afzal R.

2014-01-01

61

Evidence-based nanoscopic and molecular framework for excipient functionality in compressed orally disintegrating tablets.  

PubMed

The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2-10 µm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale. PMID:25025427

Al-Khattawi, Ali; Alyami, Hamad; Townsend, Bill; Ma, Xianghong; Mohammed, Afzal R

2014-01-01

62

Development of orally disintegrating tablets of Perphenazine/hydroxypropyl-?-cyclodextrin inclusion complex.  

PubMed

The aim of the present work was to prepare perphenazine (PPZ) orally disintegrating tablets (ODTs) based on the use of hydroxypropyl-?-cyclodextrin (HP-?-CD) forming inclusion complex with PPZ to improve the solubility and dissolution of this practically insoluble drug. Phase solubility studies were performed to evaluate the complexation of PPZ with HP-?-CD in three aqueous systems. The inclusion complex prepared by evaporation method was characterized by different physicochemical techniques, including the dissolution studies. The prepared complex was incorporated into ODTs containing different fillers and disintegrants. The ODTs prepared by direct compression were evaluated for drug content, hardness, porosity, friability, in vitro disintegration time (DT), wetting time (WT) and dissolution profiles. The solubility and dissolution rate were substantially improved compared with that of PPZ. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) analyses suggested that PPZ could form true inclusion complex with HP-?-CD. The optimized formulation F6 exhibited short DT (15.5 ± 1.9 s) and WT (34.2 ± 2.3 s), sufficient hardness (30.4 ± 1.6 N/mm) and rapid drug dissolution. The developed tablet formulation could be a promising drug delivery system with improvements in PPZ bioavailability and patient compliance. PMID:22759202

Wang, Ling; Zeng, Fan; Zong, Li

2013-01-01

63

Development and optimization of dextromethorphan hydrobromide oral disintegrating tablets: effect of formulation and process variables.  

PubMed

Orally disintegrating tablets (ODTs), which disintegrate rapidly (<1?min) in the mouth and do not require water for administration, have become a very popular dosage form. The study aims to develop a simple and inexpensive method of manufacturing ODTs of a sparingly water-soluble drug, Dextromethorphan hydrobromide. Two factors, three levels (3(2)) full factorial design was used to optimize the diluent, microcrystalline cellulose (X(1)) and superdisintegrant, croscarmellose sodium (X(2)) concentrations. Disintegration time, hardness and T(50) values for all the formulations varied from 12.5 to 152.6 s, 3.58 to 4.92 kp and 0.8 to 2.8?min, respectively. The results indicated that the selected variables have a strong influence on disintegration time, hardness and T(50) of the ODTs. The manufactured ODTs formula composed of 30% microcrystalline cellulose in combination with 3% croscarmellose sodium was chosen as optimized formula, as it showed the lowest disintegration time (12.5?±?1.22 s), low T(50) (0.8?min.) and hard tablets (4.92?±?0.28 kp) amongst other tested ODTs formulations. Hardness of DM ODTs was not affected by changing the type of superdisintegrant and lubricant. The disintegration time was significantly (p < 0.05) increased by using sodium starch glycolate instead of croscarmellose sodium. PMID:22881389

Mostafa, Haitham Fady; Ibrahim, Mohamed Abbas; Sakr, Adel

2013-01-01

64

The ACTION study: a randomized, open-label, multicenter trial comparing once-a-day extended-release morphine sulfate capsules (AVINZA) to twice-a-day controlled-release oxycodone hydrochloride tablets (OxyContin) for the treatment of chronic, moderate to severe low back pain.  

PubMed

This large, open-label, randomized, parallel-group, multicenter study compared two oral sustained-release opioids (SROs)--AVINZA (A-MQD), morphine sulfate extended-release capsules given once a day, and OxyContin (O-ER), oxycodone modified-release tablets given twice a day--in SRO-naive subjects ages 30 to 70 with chronic, moderate to severe low back pain. Of the 392 subjects enrolled and randomized, 266 (132 in the A-MQD group and 134 in the O-ER group) completed the opioid dose titration phase and entered an eight-week evaluation phase. During the evaluation phase, A-MQD achieved significantly better pain control than O-ER, as demonstrated by a greater decrease from baseline in pain scores obtained four times daily during weeks one, four, and eight (p = 0.002). The number of breakthrough-pain rescue medication doses adjusted for the number of patient days was significantly lower in the A-MQD group (p < 0.0001). Better pain control with A-MQD was achieved with a significantly lower daily opioid dose than with O-ER (mean 69.9 mg and 91 mg morphine equivalents, respectively; p = 0.0125). Quality of sleep was significantly better with A-MQD for the entire evaluation phase (p = 0.0026). The incidence and severity of elicited opioid side effects were similar in the two groups. This trial demonstrated that once-daily A-MQD provides consistent around-the-clock pain relief in patients with low back pain. In patients who completed opioid dose titration, A-MQD was significantly better than O-ER for reducing pain and improving sleep, while requiring a lower daily opioid dose. PMID:17319449

Rauck, Richard L; Bookbinder, Stephen A; Bunker, Timothy R; Alftine, Christopher D; Ghalie, Richard; Negro-Vilar, Andres; de Jong, Egbert; Gershon, Steven

2006-01-01

65

In vivo evaluation of thiolated chitosan tablets for oral insulin delivery.  

PubMed

Chitosan-6-mercaptonicotinic acid (chitosan-6-MNA) is a thiolated chitosan with strong mucoadhesive properties and a pH-independent reactivity. This study aimed to evaluate the in vivo potential for the oral delivery of insulin. The comparison of the nonconjugated chitosan and chitosan-6-MNA was performed on several studies such as mucoadhesion, release, and in vivo studies. Thiolated chitosan formulations were both about 80-fold more mucoadhesive compared with unmodified ones. The thiolated chitosan tablets showed a sustained release for 5 h for the polymer of 20 kDa and 8 h for the polymer of 400 kDa. Human insulin was quantified in rats' plasma by means of ELISA specific for human insulin with no cross-reactivity with the endogenous insulin. In vivo results showed thiolation having a tremendous impact on the absorption of insulin. The absolute bioavailabilities were 0.73% for chitosan-6-MNA of 20 kDa and 0.62% for chitosan-6-MNA 400 kDa. The areas under the concentration-time curves (AUC) of chitosan-6-MNA formulations compared with unmodified chitosan were 4.8-fold improved for the polymer of 20 kDa and 21.02-fold improved for the polymer of 400 kDa. The improvement in the AUC with regard to the most promising aliphatic thiomer was up to 6.8-fold. Therefore, chitosan-6-MNA represents a promising excipient for the oral delivery of insulin. PMID:25139279

Millotti, Gioconda; Laffleur, Flavia; Perera, Glen; Vigl, Claudia; Pickl, Karin; Sinner, Frank; Bernkop-Schnürch, Andreas

2014-10-01

66

Influence of non-water-soluble placebo pellets of different sizes on the characteristics of orally disintegrating tablets manufactured by freeze-drying.  

PubMed

The present study describes the development of an orally disintegrating tablet containing a non-water-soluble drug delivery system. A model system was applied to evaluate the effect of different-sized particles on tablet characteristics. Cellets were incorporated into tablets prepared by freeze-drying from a 100 mg/mL mannitol or sucrose solution. Particle size distributions were 200-355 µm for Cellets 200 (C200) and 500-710 µm for Cellets 500 (C500). An examination of the tablets revealed that the particles could not be sufficiently embedded in mannitol because of its crystalline nature. The tablet hardness was also inadequate. In contrast, the hardness of sucrose tablets was increased by the addition of Cellets 500. Therefore, the sucrose-based formulation was studied further. Binders [hydroxyethylstarch, sodium alginate, methylcellulose (MC), and gelatin] were added in different concentrations, and tablets were made either with or without placebo pellets. A positive effect of the Cellets on the hardness of tablets was identified. Furthermore, disintegration time could be clearly reduced by Cellets for tablets made from 100 mg/mL sucrose with addition of 10 mg/mL MC, 20 or 40 mg/mL gelatin. The freeze-dried tablet index revealed that the formulations of sucrose with 50 mg/mL hydroxyethylstarch or 20 mg/mL gelatin were particularly advantageous. PMID:23568590

Stange, Ulrike; Führling, Christian; Gieseler, Henning

2013-06-01

67

Fast and pH-dependent release of domperidone from orally disintegrating tablets.  

PubMed

There has been growing interest in orally disintegrating tablets (ODTs) during the last decade due to their better patient acceptance and compliance. Further, drug dissolution and absorption may be significantly improved. This work describes the preparation of fast and pH-dependent release ODTs for domperidone by direct compression using crospovidone as superdisintegrant. Solid dispersions of domperidone and Eudragit L100-55, at different weight ratios, were prepared and characterized by DSC, TGA, X-ray diffraction, and FTIR, which indicated the presence of drug-polymer interaction. Disintegration time, friability, and hardness of ODTs were evaluated. In vitro drug release in 0.1N HCl and in phosphate buffer (pH 5.8 and 6.8) was investigated. All domperidone ODTs had fast disintegration times (6 KP) and acceptable friability (<1%). Drug release from fast release ODTs was highly improved; reaching 97% after 10 min in 0.1N HCl, compared to the dissolution of the free drug. Drug release from solid dispersions was pH dependent; showing higher release rates at pH 6.8 than at lower pH values. The controlled-release ODT resulted in 47% drug release in 0.1N HCl, with the rest of drug released at pH 6.8. Domperidone ODTs were considered suitable for ODT formulation. PMID:22304659

Assaf, Shereen M; Qandil, Amjad M; Al-Ani, Enas A

2013-01-01

68

Orally disintegrating vardenafil tablets for the treatment of erectile dysfunction: efficacy, safety, and patient acceptability  

PubMed Central

Background: Erectile dysfunction (ED) is a well-documented medical condition that is expected to increase significantly over the next several decades, especially as men live longer and the prevalence of diabetes and cardiovascular diseases increase. Pharmacology agents are often the first line treatment approach. Newer solid dosage forms, known as orally disintegrating tablets (ODT), are now available as one treatment option. Objectives: To review the drug delivery mechanisms of ODTs in general and to review safety and efficacy of vardenafil ODT (a PDE-5 inhibitor) as a treatment option for management of ED. Method: Literature reviews were performed of pharmaceutical dosage forms and the POTENT I (n = 358 subjects) and POTENT II (n = 337 subjects) studies that investigated vardenafil ODT. Results: Vardenafil ODT has been successfully used in multiple age groups and in multiple settings with men from various ethnic backgrounds. Efficacy of vardenafil ODT, as measured using the International Index of Erectile Function (IIEF-EF) and from the Sexual Encounter Profile (SEP) was significantly greater than placebo (P < 0.0001) at 12 weeks. Safety profiles were similar to film-coated dosage forms with no patient deaths reported. Conclusion: Vardenafil ODT offers a convenient, ready-to-use approach for combating ED. Safety concerns are similar to other PDE-5 inhibitors and practitioners should counsel patients accordingly. PMID:21573049

Green, Roger; Hicks, Rodney W

2011-01-01

69

Freeze drying of orally disintegrating tablets containing taste masked naproxen sodium granules in blisters.  

PubMed

Abstract Orally disintegrating tablets (ODTs) were freeze dried in blisters using the Lyostar® II SMART™ Freeze Dryer Technology. ODT formulations either without non-water soluble particles (placebo) or containing large fractions (717?mg) of taste-masked naproxen sodium (NaS) granules were freeze dried. The process data revealed differences between ODTs with and without embedded granules in the pressure rise curves as well as in the shelf (inlet) temperature adjustments during freeze-drying. Pressure rise curves of the placebo ODTs from eight hours process time showed no distinct temperature-dominated part, and the last optimization step of the shelf temperature to achieve -24.4?°C might be prone to errors. The final shelf temperature of ODTs containing granules was -23.3?°C. The detection of primary drying endpoints using SMART™ Technology or comparative pressure measurements was reliable for both ODT formulations, whereas the application of thermocouples resulted in premature endpoint indication. Product resistance of ODTs containing granules was generally elevated in comparison to ODTs without granules, but increased only slightly over the course of the drying process. In summary, the developed freeze-drying cycle was found applicable for production of elegant ODTs with incorporated taste masked NaS granules. PMID:25220888

Stange, Ulrike; Führling, Christian; Gieseler, Henning

2014-09-15

70

Influence of Prosolv and Prosolv:Mannitol 200 direct compression fillers on the physicomechanical properties of atorvastatin oral dispersible tablets.  

PubMed

Abstract The objective of the present study was to evaluate the influence of Prosolv® and Prosolv®: Mannitol 200 direct compression (DC) fillers on the physicomechanical characteristics of oral dispersible tablets (ODTs) of crystalline atorvastatin calcium. ODTs were formulated by DC and were analyzed for weight uniformity, hardness, friability, drug content, disintegration and dissolution. Three disintegration time (DT) test methods; European Pharmacopoeia (EP) method for conventional tablets (Method 1), a modification of this method (Method 2) and the EP method for oral lyophilisates (Method 3) were compared as part of this study. All ODTs showed low weight variation of <2.5%. Prosolv® only ODTs showed the highest tablet hardness of ?73?N, hardness decreased with increasing mannitol content. Friability of all formulations was <1% although friability of Prosolv®:Mannitol ODTs was higher than for pure Prosolv®. DT of all ODTs was <30?s. Method 2 showed the fastest DT. Method 3 was non-discriminatory giving a DT of 13-15?s for all formulations. Atorvastatin dissolution from all ODTs was >60% within 5?min despite the drug being crystalline. Prosolv® and Prosolv®:Mannitol-based ODTs are suitable for ODT formulations by DC to give ODTs with high mechanical strength, rapid disintegration and dissolution. PMID:24397821

Gowda, Veeran; Pabari, Ritesh M; Kelly, John G; Ramtoola, Zebunnissa

2014-01-01

71

RP-HPLC analytical method development and optimization for quantification of donepezil hydrochloride in orally disintegrating tablet.  

PubMed

An easy, fast and validated RV-HPLC method was invented to quantify donepezil hydrochloride in drug solution and orally disintegrating tablet. The separation was carried out using reversed phase C-18 column (Agilent Eclipse Plus C-18) with UV detection at 268 nm. Method optimization was tested using various composition of organic solvent. The mobile phase comprised of phosphate buffer (0.01M), methanol and acetonitrile (50:30:20, v/v) adjusted to pH 2.7 with phosphoric acid (80%) was found as the optimum mobile phase. The method showed intraday precision and accuracy in the range of 0.24% to -1.83% and -1.83% to 1.99% respectively, while interday precision and accuracy ranged between 1.41% to 1.81% and 0.11% to 1.90% respectively. The standard calibration curve was linear from 0.125 ?g/mL to 16 ?g/mL, with correlation coefficient of 0.9997±0.00016. The drug solution was stable under room temperature at least for 6 hours. System suitability studies were done. The average plate count was > 2000, tailing factor <1, and capacity factor of 3.30. The retention time was 5.6 min. The HPLC method was used to assay donepezil hydrochloride in tablet and dissolution study of in-house manufactured donepezil orally disintegrating tablet and original Aricept. PMID:24035953

Liew, Kai Bin; Peh, Kok Khiang; Fung Tan, Yvonne Tze

2013-09-01

72

Formulation and evaluation of meloxicam oral disintegrating tablet with dissolution enhanced by combination of cyclodextrin and ion exchange resins.  

PubMed

Abstract Context: The bitter taste of drug is masked by the exchange of ionized drugs with counter ions of ion exchange resin, forming "resinate". Cyclodextrin reduces the unpleasant taste and enhances the drug solubility by encapsulating drug molecules into its central cavity. Objective: Oral disintegrating tablets (ODTs) using the combination of ion exchange resin and cyclodextrin was developed, to mask the bitter taste and enhance drug dissolution. Methods: Meloxicam (MX) was selected as a model drug. Formulations containing various forms of MX (free drug, MX-loaded resin or resinate, complexes of MX and 2-hydroxypropyl-?-cyclodextrin (HP?CD) or MX/HP?CD complexes, and a mixture of resinate and MX/HP?CD complexes) were made by direct compression. The ODTs were evaluated for weight variation, thickness, diameter, hardness, friability, disintegration time, wetting time, MX content, MX release, degree of bitter taste and stability. Results and discussion: The tablet hardness was ?3?kg/in(2), and the friability was <1%. Tablets formulated with resinate and the mixture of resinate and MX/HP?CD complexes disintegrated rapidly within 60?s, which is the acceptable limit for ODTs. These results were corresponded to the in vivo disintegration and wetting times. However, only tablets containing the mixture of resinate and MX/HP?CD complexes provided complete MX dissolution and successfully masked the bitter taste. In addition, this tablet was stable at least 6 months. Conclusions: The combination of ion exchange resin and cyclodextrin could be used in ODTs to mask the bitter taste and enhance the dissolution of drugs that are weakly soluble in water. PMID:24865111

Samprasit, Wipada; Akkaramongkolporn, Prasert; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Opanasopit, Praneet

2014-05-28

73

Population pharmacokinetics of levodopa in subjects with advanced Parkinson's disease: levodopa-carbidopa intestinal gel infusion vs. oral tablets  

PubMed Central

Aims Levodopa-carbidopa intestinal gel (LCIG) provides continuous levodopa-carbidopa delivery through intrajejunal infusion. This study characterized the population pharmacokinetics of levodopa following a 16 h jejunal infusion of LCIG or frequent oral administration of levodopa-carbidopa tablets (LC-oral) in subjects with advanced Parkinson's disease (PD). Methods A non-linear mixed-effects model of levodopa pharmacokinetics was developed using serial plasma concentrations from an LCIG phase 1 study and a phase 3 double-blind, double-dummy study of the efficacy and safety of LCIG compared with LC-oral in advanced PD patients (n = 68 for model development; 45 on LCIG and 23 on LC-oral). The final model was internally evaluated using stochastic simulations and bootstrap and externally evaluated using sparse pharmacokinetic data from 311 subjects treated in a long term safety study of LCIG. Results The final model was a two compartment model with a transit compartment for absorption, first order elimination, bioavailability for LCIG (97%; confidence interval = 95% to 98%) relative to LC-oral, different first order transit absorption rate constants (LCIG = 9.2 h–1 vs. LC-oral = 2.4 h–1; corresponding mean absorption time of 7 min for LCIG?vs. 25 min for LC-oral) and different residual (intra-subject) variability for LCIG (15% proportional error, 0.3 ?g ml?1 additive error) vs.?LC-oral (29% proportional error, 0.59 ?g ml?1 additive error). Estimated oral clearance and steady-state volume of distribution for levodopa were 24.8 l h?1 and 131 l, respectively. Conclusions LCIG administration results in faster absorption, comparable levodopa bioavailability and significantly reduced intra-subject variability in levodopa concentrations relative to LC-oral administration. PMID:24433449

Othman, Ahmed A; Dutta, Sandeep

2014-01-01

74

Preparation and characterisation of Kolliphor® P 188 and P 237 solid dispersion oral tablets containing the poorly water soluble drug disulfiram.  

PubMed

The oral route of administration is the most common and preferred route of drug delivery due to its ease of administration, cost-effectiveness and flexibility in design. However, limited aqueous solubility of the active pharmaceutical ingredient can result in poor bioavailability, which is a major issue for the pharmaceutical industry. Increasing numbers of new drugs are falling into class II of the Biopharmaceutical Classification System (BCS), where they have a low solubility and high tissue permeability, meaning that bioavailability is solubility dependent. Here we demonstrate the development and characterisation of solid dispersion oral tablets, containing the poorly water-soluble drug disulfiram, prepared using both the hot melt and solvent evaporation methods and manufactured from two different polymers, Kolliphor(®) P 188 and P 237, specifically designed for the manufacture of solid dispersions. This paper demonstrates that the disulfiram solid dispersions tablets have an enhanced release rate of disulfiram compared to the control tablets. The Kolliphor(®) P 188 polymer control tablets released approximately 48.8% of their disulfiram content over 8h, with the solvent evaporated tablets releasing approximately 65.8%, while the 60 and 80 °C hot melt tablets released approximately 73.2 and 100% of their disulfiram content respectively. A similar trend was seen with Kolliphor(®) P 237 as the control tablets released approximately 50.5% of their disulfiram content over 8h, while the solvent evaporated tablets released approximately 79.5% and the 60 and 80 °C hot melt tablets released 100.2 and 100.3% respectively. Depending on what method and polymer is used to manufacture the solid dispersions the disulfiram is either maintained completely or partially in its amorphous state and it is this which enhances its solubility and release rate from the tablets. The disulfiram in the Kolliphor(®) P 188 solvent evaporated and 60 °C hot melt tablets retained 50.5 and 44.1% of its crystallinity, while the disulfiram in the 80 °C hot melt tablets was completely amorphous. Whereas the disulfiram in the Kolliphor(®) P 237 solvent evaporated tablets retained 45.2% crystallinity, while the disulfiram in both of the hot melt tablets was completely in its amorphous form. PMID:25218186

Ramadhani, Nisrina; Shabir, Mehwish; McConville, Christopher

2014-11-20

75

Differential pharmacokinetics and the brain distribution of morphine and ephedrine constitutional isomers in rats after oral administration with Keke capsule using rapid-resolution LC-MS/MS.  

PubMed

Opioid and ephedra alkaloids known as the active ingredients for Keke capsule, which is used to treat coughs and bronchial asthma, could have potential adverse effects on the central nervous system. Therefore, an efficient, sensitive rapid-resolution LC-MS/MS method for the simultaneous determination of morphine, ephedrine, and pseudoephedrine in rat plasma and brain tissue homogenate has been developed. The method was validated in the plasma and brain tissue samples, showed good linearity over a wide concentration range (r(2) > 0.99). The intra- and interday assay variability was less than 15% for all analytes, and the accuracy was between -8.8 and 5.7%. The study provided the pharmacokinetics profiles and the brain regional distribution of the three active alkaloids after oral administration of Keke capsule. The results also indicated that significant difference in pharmacokinetics parameters of the epimers was observed between ephedrine and pseudoephedrine. PMID:24318005

Song, Yonggui; Su, Dan; Lu, Tulin; Mao, Chunqin; Ji, De; Liu, Yali; Wei, Binbin; Fan, Ronghua

2014-02-01

76

21 CFR 520.1284 - Sodium liothyronine tablets.  

Code of Federal Regulations, 2010 CFR

...Specifications. Sodium liothyronine tablets consist of tablets intended for oral administration...liothyronine at 60 or 120 micrograms per tablet, as the sodium salt. (b...orally to dogs at levels up to 12.8 micrograms per...

2010-04-01

77

Urinary Excretion and Metabolism of Arbutin after Oral Administration of Arctostaphylos uvae ursi Extract as Film-Coated Tablets and Aqueous Solution in Healthy Humans  

Microsoft Academic Search

Bearberry leaves and preparations made from them are traditionally used for urinary tract infections. The urinary excretion of arbutin metabolites was examined in a randomized crossover design in 16 healthy volunteers after the application of a single oral dose of bearberry leaves dry extract (BLDE). There were two groups of application using either film-coated tablets (FCT) or aqueous solution (AS).

Gernot Schindler; Ulrich Patzak; Benno Brinkhaus; Alexander von Nieciecki; Jörg Wittig; Nils Krähmer; Ingmar Glöckl; Markus Veit

2002-01-01

78

A randomized clinical trial comparing doses and efficacy of lormetazepam tablets or oral solution for insomnia in a general practice setting.  

PubMed

Lormetazepam is a short-acting benzodiazepine hypnotic which is beneficial in shortening the time to onset of sleep. The aim of the study was to assess a new formulation of lormetazepam (oral solution) in comparison with lormetazepam tablets in out-patients with insomnia. This trial was an open randomized parallel group study conducted by 30 general practitioners. One hundred and eight patients took 0.5 mg on the first night and were allowed to increase their dosage by 0.25 mg (for oral solution) and 0.5 mg (for tablets), respectively, each day and every 2 days. The patients assessed the efficacy, acceptability and tolerance of lormetazepam using a diary card and a set of visual analogue scales assessing their sleep. Over 14 days of treatment, the mean daily dose of lormetazepam was lower in the oral solution group than in the tablets group (0.78 mg versus 0.97 mg). The cumulated dose of lormetazepam was lower with the oral solution (18% reduction). No significant difference between the two groups was found in the assessment of sleep characteristics. The occurrence of side effects did not differ between the two groups. These results suggest that a unitary dose as achieved by an oral solution of lormetazepam allows easier determination of the minimal individual effective dose. PMID:14994324

Ancolio, C; Tardieu, S; Soubrouillard, C; Alquier, C; Pradel, V; Micallef, J; Blin, O

2004-03-01

79

Comparing the Therapeutic Effects of Garlic Tablet and Oral Metronidazole on Bacterial Vaginosis: A Randomized Controlled Clinical Trial  

PubMed Central

Background: Bacterial vaginosis (BV) is one of the most common gynecological infections during reproductive age. Although metronidazole is one of the most effective medications recommended as the first-line treatment, it has various side effects. Because of the side effects and contraindications of some chemical medicines, using herbs has been investigated in treating BV. Objectives: The aim of this study was to compare the effect of garlic tablet (Garsin) and oral metronidazole in clinical treatment of the BV in women referred to Resalat Health Center, affiliated with Mazandaran University of Medical Sciences, in 2013. Patients and Methods: This randomized clinical trial was conducted on 120 married women aged 18 to 44 years who were diagnosed with BV by Amsel’s clinical criteria and Gram staining. Enrolled women were randomly allocated to two groups of 60 patients and were treated with either garlic tablet or oral metronidazole for seven days. Amsel’s criteria and Gram stain were assessed seven to ten days after beginning the treatment period and side effects were registered. Results: Amsel’s criteria were significantly decreased after treatment with garlic or metronidazole (70% and 48.3%, respectively; P < 0.001). Therapeutic effects of garlic on BV were similar to that of metronidazole (63.3% and 48.3%, respectively; P = 0.141). There were significant differences between the two treatment groups in terms of side effects; metronidazole was associated with more complications (P = 0.032). Conclusions: This study reveals that garlic could be a suitable alternative for metronidazole in treatment of BV in those interested in herbal medicines or those affected by side effects of metronidazole. PMID:25237588

Mohammadzadeh, Farnaz; Dolatian, Mahrokh; Jorjani, Masoome; Alavi Majd, Hamid; Borumandnia, Nasrin

2014-01-01

80

Comparison of the pharmacokinetics of miconazole after administration via a bioadhesive slow release tablet and an oral gel to healthy male and female subjects  

PubMed Central

Aims The aim of this study was to compare salivary miconazole pharmacokinetics following once daily application of bioadhesive tablets (50 or 100 mg), vs the current treatment with a gel (3 times a day, 375 mg day?1). Methods A three way cross over study was carried out in 18 healthy subjects (nine males, nine females) with a 1 week washout period between each treatment. Plasma and salivary pharmacokinetics of miconazole were assessed over a 24-h period. Results In all subjects the tablets gave higher and more prolonged salivary miconazole concentrations than the gel. Thus salivary miconazole AUC(0,24 h) was 37.2 times greater for the 100 mg tablet (90% confidence interval [CI] 22.9, 60.5) and 18.9 times greater for the 50 mg tablet (CI 11.7, 30.6) compared with the gel. Similarly, Cmax was 17.2 times greater (CI 11.8, 25.2) and 7.8 times greater (CI 5.3, 11.4) for the 100 mg tablet and 50 mg tablet, respectively. Comparison of the 100 mg and 50 mg tablets gave ratios of 2.2 and 2.0 for Cmax and AUC(0,24 h), respectively (CI 1.5, 3.2 and 1.2, 3.2). The mean time that salivary miconazole concentrations were above 0.4 µg ml?1 (the concentration reached 3 h after application of the oral gel according to published data) or above 1.0 µg ml?1 (the MIC of some Candida species) was greater for both bioadhesive tablets than for the oral gel (10–14 h vs 1.5 h and 7 h vs 0.6 h). Only 19 plasma samples from eight subjects had concentrations of miconazole above 0.4 µg ml?1. Ten of these were taken from five subjects after administration of the gel and nine from three subjects after administration of the tablets. Conclusions These data strongly support the further development of miconazole bioadhesive tablets as a sustained release formulation leading to improved antifungal exposure in the buccal cavity. A single daily application should improve compliance, whereas the low systemic absorption of miconazole will alleviate concerns regarding drug interactions and adverse effects. PMID:15373926

Cardot, J-M; Chaumont, C; Dubray, C; Costantini, D; Aiache, J-M

2004-01-01

81

Safety of fluralaner chewable tablets (BravectoTM), a novel systemic antiparasitic drug, in dogs after oral administration  

PubMed Central

Background Fluralaner is a novel systemic insecticide and acaricide that provides long acting efficacy in dogs after a single oral treatment. This study investigated the safety of oral administration of fluralaner in chewable tablets to dogs at the highest recommended treatment dose and at multiples of this dose. Methods Thirty-two (16 male and 16 female) healthy 8-week old Beagle dogs weighing 2.0 - 3.6 kg at first administration were included in the study. Fluralaner was administered on three occasions at 8-week intervals at doses of up to 56, 168, and 280 mg fluralaner/kg body weight, equivalent to 1, 3, and 5 times the highest recommended treatment dose of fluralaner; sham dosed dogs served as controls. During the study, all dogs were clinically observed, and their health was carefully monitored including body weight development, food consumption and measurement of hematology, coagulation, clinical chemistry (including measurement of levels of ACTH and C-reactive protein) and urinalysis. Following euthanasia of the dogs, complete gross post mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted. Results There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology parameters and organ weights; none of these findings were considered to be of clinical relevance. Conclusions Oral administration of fluralaner at the highest recommended treatment dose (56 mg/kg) at 8-week intervals is well tolerated and has a safety margin of more than five in healthy dogs eight weeks of age or older and weighing at least 2 kg. PMID:24606886

2014-01-01

82

Formulation Optimization of Hydrodynamically Balanced Oral Controlled Release Bioadhesive Tablets of Tramadol Hydrochloride  

PubMed Central

The directly compressible floating-bioadhesive tablets of tramadol were formulated using varying amounts Carbopol 971P (CP) and hydroxy-propylmethyl cellulose (HPMC), along with other requisite excipients. In vitro drug release profile, floatational characteristics and ex vivo bioadhesive strength using texture analyzer were determined, and systematically optimized using a 32 central composite design (CCD). The studies indicated successful formulation of gastroretentive compressed matrices with excellent controlled release, mucoadhesion and hydrodynamic balance. Comparison of the dissolution profiles of the optimized formulation, with optimal composition of CP:HPMC :: 80.0:125.0, with that of the marketed controlled release formulation other indicated analogy of drug release performance with each other. Validation of optimization study using eight confirmatory experimental runs indicated very high degree of prognostic ability of CCD with mean ± SEM of ?0.06% ± 0.37. Further, the study successfully unravels the effect of the polymers on the selected response variables. PMID:21179349

Singh, Bhupinder; Rani, Ashu; Babita; Ahuja, Naveen; Kapil, Rishi

2010-01-01

83

In vitro and in vivo equivalence of two oral atenolol tablet formulations.  

PubMed

A randomised, cross-over, open study of bioequivalence between two different atenolol (CAS 29122-68-7) tablet formulations is presented. An in vitro comparative study between the two formulations was also performed. Both products meet the USP 23 (United States Pharmacopea) specification. The values of similarity factor (f2) and difference factor (f1) obtained ensure sameness or equivalence of the two dissolution curves. Twenty-four healthy volunteers (male/female) participated in the bioequivalence study. Each treatment was given as a single 100-mg tablet following an overnight fast. Atenolol concentrations in plasma were determined up to 30 h after treatment by HPLC. The pharmacokinetic parameters AUC0-infinity, Cmax and Cmax/AUC0-infinity were tested for bioequivalence after logarithmic transformation of data and ratios of tmax were evaluated nonparametrically. The parametric analysis revealed the following test/reference ratios and their 90% confidence intervals (90% CI): 1.06 (0.99-1.13) for AUC, 1.07 (0.97-1.18) for Cmax, and 0.99 (0.94-1.07) for Cmax/AUC0-infinity. The 90% CI for tmax was 0.91-1.23. All parameters showed bioequivalence between both formulations. A discrete fall in both systolic (SBP) and diastolic (DBP) blood pressure was observed after the drug administration. The fall extent (approximately 11 mmHg in supine position) and the time course of both parameters after the drug administration was similar for both formulations. Minimal values for SBP and DBP were achieved at 6 h after the drug administration for both formulations. Heart rates were also reduced after the administration of both formulations of atenolol in a similar extent (12 b.p.m.) and following a similar time profile (i.e. maximal reductions were observed between 1 and 3 h after the drug administration). It can be concluded that both formulations are equivalent in vitro and in vivo. PMID:12087922

Cuadrado, Antonio; Rodríguez Gascón, Alicia; Hernández, Rose María; Castilla, Ana María; de la Maza, Ane; López de Ocáriz, Alicia; Calvo, Begoña; Pedraz, José Luis

2002-01-01

84

Comparative Studies on the Dissolution Profiles of Oral Ibuprofen Suspension and Commercial Tablets using Biopharmaceutical Classification System Criteria  

PubMed Central

In vitro dissolution studies for solid oral dosage forms have recently widened the scope to a variety of special dosage forms such as suspensions. For class II drugs, like Ibuprofen, it is very important to have discriminative methods for different formulations in physiological conditions of the gastrointestinal tract, which will identify different problems that compromise the drug bioavailability. In the present work, two agitation speeds have been performed in order to study ibuprofen suspension dissolution. The suspensions have been characterised relatively to particle size, density and solubility. The dissolution study was conducted using the following media: buffer pH 7.2, pH 6.8, 4.5 and 0.1 M HCl. For quantitative analysis, the UV/Vis spectrophotometry was used because this methodology had been adequately validated. The results show that 50 rpm was the adequate condition to discriminate the dissolution profile. The suspension kinetic release was found to be dependent on pH and was different compared to tablet release profile at the same experimental conditions. The ibuprofen release at pH 1.0 was the slowest. PMID:23626386

Rivera-Leyva, J. C.; García-Flores, M.; Valladares-Méndez, A.; Orozco-Castellanos, L. M.; Martínez-Alfaro, M.

2012-01-01

85

21 CFR 520.2158b - Dihydrostreptomycin tablets.  

Code of Federal Regulations, 2010 CFR

...false Dihydrostreptomycin tablets. 520.2158b Section...AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2158b Dihydrostreptomycin tablets. (a) Specifications. Each tablet contains 37.5...

2010-04-01

86

Emerging oral treatments in multiple sclerosis – clinical utility of cladribine tablets  

PubMed Central

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) that represents one of the first causes of neurological disability in young adults. Although the pathogenesis of MS is still unclear, an autoimmune mechanism has been demonstrated. According to this evidence in the last 15 years different treatments acting on the immune system have been developed. Current disease-modifying drugs (DMDs) for MS require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Moreover the clinical efficacy of these disease-modifying drugs is suboptimal. Thus, there is an important need for the development of new therapeutic strategies. Several oral therapies (fingolimod, fumaric acid, teriflunomide, laquinimod) are in development; Among these cladribine is the only therapy with the potential for short-course dosing. Cladribine is an immunosuppressant that offers sustained regulation of the immune system through a preferential lymphocyte depleting action. Cladribine has a well-characterized and well-known safety profile, derived from more than 15 years of use of the parenteral formulation both in the oncology field and in MS. This paper reviews the new oral emerging treatments and presents the available data about the use of cladribine in MS and the future perspective of its clinical use. PMID:20856685

Gasperini, Claudio; Ruggieri, Serena; Pozzilli, Carlo

2010-01-01

87

Pharmacokinetics of metronidazole, tetracycline and bismuth in healthy volunteers after oral administration of compound tablets containing a combination of metronidazole, tetracycline hydrochloride and bismuth oxide.  

PubMed

To eradicate Helicobacter pylori in human pylorus and to heal duodenal ulcers, recently, a new formulation of combination tablets containing metronidazole 125?mg, tetracycline hydrochloride 125?mg and bismuth oxide 40?mg has been developed.To investigate the pharmacokinetics of metronidazole, tetracycline and bismuth in healthy Chinese volunteers after oral administration of the test formulation.A one-sequence, 3-period study was conducted in 12 Chinese healthy volunteers (6 male, 6 female). Volunteers each received single low dose (1 tablet) under fed condition in period 1, single high dose (3 tablets) under fasted condition in period 2, and single high dose (3 tablets) and multiple doses (3 tablets at once, 4 times daily for 7 consecutive days) under fed condition in period 3. Blood samples were collected and determined over 48?h in every period.After single high dose administration under fed condition, the C max of metronidazole, tetracycline and bismuth were 6.833±0.742??g/mL, 0.8513±0.1253??g/mL and 3.32±1.89?ng/mL, respectively. The C max and AUC 0-48 of metronidazole increased in proportion to the doses within the tested dose range, but tetracycline and bismuth did not. Food caused 10% and 80% decrease of the C max for metronidazole and bismuth, respectively, but did not affect tetracycline. No gender effect was found on the pharmacokinetics of the 3 ingredients. In the steady state, the C av of metronidazole, tetracycline and bismuth were 20.75±3.52??g/mL, 1.900±0.243??g/mL and 5.61±1.34?ng/mL, respectively. PMID:24764254

Wu, Y; Ding, L; Huang, N-Y; Wen, A-D; Liu, B; Li, W-B

2015-02-01

88

A novel pH-responsive interpolyelectrolyte hydrogel complex for the oral delivery of levodopa. Part II: Characterization and formulation of an IPEC-based tablet matrix.  

PubMed

This study was undertaken in order to apply a synthesized interpolyelectrolyte complex (IPEC) of polymethacrylate and carboxymethylcellulose as a controlled release oral tablet matrix for the delivery of the model neuroactive drug levodopa. The IPEC (synthesized in Part I of this work) was characterized by techniques such as Fourier Transform Infra-Red (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), Advanced DSC (ADSC), and Scanning Electron Microscopy (SEM). The tablet matrices were formulated and characterized for their drug delivery properties and in vitro drug release. FTIR confirmed the interaction between the two polymers. The IPEC composite generated tablet matrices with a hardness ranging from 19.152-27.590 N/mm and a matrix resilience ranging between 42 and 46%. An IPEC of polymethacrylate and carboxymethylcellulose was indeed an improvement on the inherent properties of the native polymers providing a biomaterial with the ability to release poorly soluble drugs such as levodopa at a constant rate over a prolonged period of time. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1085-1094, 2015. PMID:24909309

Ngwuluka, Ndidi C; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Khan, Riaz A; Pillay, Viness

2015-03-01

89

The effects of screw configuration and polymeric carriers on hot-melt extruded taste-masked formulations incorporated into orally disintegrating tablets.  

PubMed

The primary aim of this research was to produce successfully taste masked formulations of Sildenafil Citrate (SC) using hot-melt extrusion (HME) technology. Multiple screw configurations and polymeric carriers were evaluated for their effects on taste masking efficiency, which was assessed by both E-tongue analysis and in vitro dissolution in simulated salivary fluid (SSF, pH 6.8 artificial saliva). The screw configurations were further assessed for their effects on the morphology of the API using PXRD, FT-IR and mid-infrared chemical imaging. It was determined that the screw configuration had a profound effect on the taste masking efficiency of the formulations as a result of altering the physical state of the API. Selected extruded formulations using ethylcellulose (EC) with a pore former were further formulated into orally disintegrating tablets (ODTs), which were optimized by varying the grade and percentage of the superdisintegrant used. An optimized disintegration time of approximately 8 seconds was achieved. The final ODT formulation exhibited excellent taste masking properties with over 85% drug release in gastric media as well as physical tablet properties. Interestingly, friability, which tends to be a common concern when formulating ODTs, was well within the acceptable limits (<1%) for common tablets. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:124-134, 2015. PMID:25410968

Morott, Joseph T; Pimparade, Manjeet; Park, Jun-Bom; Worley, Chelsea P; Majumdar, Soumyajit; Lian, Zhuoyang; Pinto, Elanor; Bi, Yunxia; Durig, Thomas; Repka, Michael A

2015-01-01

90

Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method  

PubMed Central

Pharmacokinetic characters of rhynchophylline (RIN), gastrodin (GAS), and gastrodigenin (p-hydroxybenzyl alcohol, HBA) were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT) and gouteng (rhynchophylla alkaloids, EPG). At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters Cmax and AUC0–? (P < 0.05) were dramatically different after oral administration of different prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components in Yizhi. The rationality of the compatibility of Uncaria and Gastrodia elata as a classic “herb pair” has been verified from the pharmacokinetic viewpoint. PMID:25610474

Ge, Zhaohui; Liang, Qionglin; Wang, Yiming; Luo, Guoan

2014-01-01

91

Pharmacokinetic Comparative Study of Gastrodin and Rhynchophylline after Oral Administration of Different Prescriptions of Yizhi Tablets in Rats by an HPLC-ESI/MS Method.  

PubMed

Pharmacokinetic characters of rhynchophylline (RIN), gastrodin (GAS), and gastrodigenin (p-hydroxybenzyl alcohol, HBA) were investigated after oral administration of different prescriptions of Yizhi: Yizhi tablets or effective parts of tianma (total saponins from Gastrodiae, EPT) and gouteng (rhynchophylla alkaloids, EPG). At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parameters C max and AUC0-? (P < 0.05) were dramatically different after oral administration of different prescriptions of Yizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components in Yizhi. The rationality of the compatibility of Uncaria and Gastrodia elata as a classic "herb pair" has been verified from the pharmacokinetic viewpoint. PMID:25610474

Ge, Zhaohui; Xie, Yuanyuan; Liang, Qionglin; Wang, Yiming; Luo, Guoan

2014-01-01

92

Single blind comparison of ketoconazole 200 mg oral tablets and clotrimazole 100 mg vaginal tablets and 1% cream in treating acute vaginal candidosis.  

PubMed

A single blind study of 103 women with vaginal candidosis was undertaken to compare treatment with conventional topical clotrimazole and oral ketoconazole. Both treatment regimens were equally effective in terms of clinical symptoms, negative results on culture for Candida albicans, and relapse rates. As treatment for vaginal candidosis takes several days, patient compliance is important and the success of a treatment regimen may depend on its acceptability to patients. Those in this study who had previously been treated for vaginal candidosis were asked to compare their current and previous treatments. Significantly more (p less than 0.001) of those treated with ketoconazole than those treated with clotrimazole found it more acceptable than previous treatment. This indicated a strong preference for oral treatment, and oral antifungal agents may be the treatment of choice for vaginal candidosis in the future. PMID:6329405

Bingham, J S

1984-06-01

93

Pharmacokinetic and bioequivalence comparison between orally disintegrating and conventional tablet formulations of flurbiprofen: A single-dose, randomized-sequence, open-label, two-period crossover study in healthy chinese male volunteers  

Microsoft Academic Search

Background: Flurbiprofen, an NSAID, is used for the treatment of inflammation and pain caused by rheumatoid arthritis and osteoarthritis as well as soft-tissue injuries. A new orally disintegrating tablet (ODT) of flurbiprofen has recently been developed; this study was conducted to provide support for this drug to obtain marketing authorization in China.Objective: The aim of the study was to compare

Yan-Mei Liu; Gang-Yi Liu; Yun Liu; Shui-Jun Li; Jing-Ying Jia; Meng-Qi Zhang; Chuan Lu; Yong-Mei Zhang; Xue-Ning Li; Chen Yu

2009-01-01

94

Double-Layered Mucoadhesive Tablets Containing Nystatin  

Microsoft Academic Search

The objective of this work was to design a mucoadhesive tablet with a potential use in the treatment of oral candidosis. A 2-layered tablet containing nystatin was formulated. Lactose CD (direct compression), carbomer (CB), and hydroxypropylmethylcellulose (HPMC) were used as excipients. Tablets were obtained through direct compression. Properties such as in vitro mucoadhesion, water uptake, front movements, and drug release

Juan Manuel Llabot; Ruben Hilario Manzo; Alberto allemandi

2002-01-01

95

Successful management of a difficult cancer pain patient by appropriate adjuvant and morphine titration.  

PubMed

Morphine has been used for many years to relieve cancer pain. Oral morphine (in either immediate release or modified release form) remains the analgesic of choice for moderate or severe cancer pain. The dose of oral morphine is titrated up to achieve adequate relief from pain with minimal side effects. Antidepressant and anticonvulsant drugs, when used in addition to conventional analgesics, give excellent relief from cancer pain. Most cancer pain responds to pharmacological measures with oral morphine but some pain like neuropathic and bony pain, pain in children and elderly age group, and advanced malignancy pain are very difficult to treat. Here, we report the management of a similar patient of severe cancer pain and the difficulty that we came across during dose titration of oral morphine and adjuvant analgesic. PMID:21976860

Rana, Shiv Ps; Ahmed, Arif; Kumar, Vindo; Chaudhary, Prakash K; Khurana, Deepa; Mishra, Seema

2011-05-01

96

Successful Management of a Difficult Cancer Pain Patient by Appropriate Adjuvant and Morphine Titration  

PubMed Central

Morphine has been used for many years to relieve cancer pain. Oral morphine (in either immediate release or modified release form) remains the analgesic of choice for moderate or severe cancer pain. The dose of oral morphine is titrated up to achieve adequate relief from pain with minimal side effects. Antidepressant and anticonvulsant drugs, when used in addition to conventional analgesics, give excellent relief from cancer pain. Most cancer pain responds to pharmacological measures with oral morphine but some pain like neuropathic and bony pain, pain in children and elderly age group, and advanced malignancy pain are very difficult to treat. Here, we report the management of a similar patient of severe cancer pain and the difficulty that we came across during dose titration of oral morphine and adjuvant analgesic. PMID:21976860

Rana, Shiv PS; Ahmed, Arif; Kumar, Vindo; Chaudhary, Prakash K; Khurana, Deepa; Mishra, Seema

2011-01-01

97

Single- and multiple-dose pharmacokinetics of a novel tetramethylpyrazine reservoir-type transdermal patch versus tetramethylpyrazine phosphate oral tablets in healthy normal volunteers, and in vitro/in vivo correlation.  

PubMed

A novel reservoir-type transdermal system of 2,3,5,6-tetramethylpyrazine (TMP) was developed containing eucalyptus oil as a penetration enhancer. The single and multiple-dose pharmacokinetic profiles of TMP administrated by TMP transdermal patch were characterized in healthy volunteers using an in vivo, randomized, open-label, two-way crossover design. 2,3,5,6-Tetramethylpyrazine phosphate (TMPP) oral tablets were chosen as reference. Following single/multiple oral administration of 200/100 mg TMPP tablets, a TMP C(max) of 1284/613.5 ng/mL was observed within 0.75 h. Single/multiple applications of the TMP patch yielded mean C(max) of 309/325 ng/mL at a median T(max) of 5/4 h, with steady state achieved at second application. The mean C(min) of the patch was 131±30.38 ng/mL, contrasting to nearly zero for the tablet. Multiple applications of patch produced an accumulative effect over single application. At steady state 250 mg/20 cm(2) TMP patch given daily provided comparable exposure to 100 mg TMPP tablets three times daily (3753.91 versus 3563.67 ng·h/mL). TMP tablets and patch yielded similar steady-state plasma concentrations: C(av) (148.48±51.27, 156.41±40.31 ng/mL). The results demonstrated that TMP patch can achieve a therapeutic effect that is comparable to oral administration, exhibited prolonged and sustained plasma levels, fewer drug fluctuations, lower adverse effects, more convenience, and improved patient compliance. In-vitro permeation through human skin demonstrated zero-order kinetics with the flux of 364 µg/cm(2)/h. The predicted C(av) (163.9 ng/mL) was in agreement with the observed C(av) (156.4 ng/mL). PMID:23514701

Shen, Teng; Xu, Huinan; Weng, Weiyu; Zhang, Jianfang

2013-01-01

98

In vitro and in vivo correlation of disintegration and bitter taste masking using orally disintegrating tablet containing ion exchange resin-drug complex.  

PubMed

Although the taste-masking of bitter drug using ion exchange resin has been recognized, in vitro testing using an electronic tongue (e-Tongue) and in vivo bitterness test by human panel test was not fully understood. In case of orally disintegrating tablet (ODT) containing bitter medicine, in vitro and in vivo disintegration is also importance for dosage performance. Donepezil hydrochloride was chosen as a model drug due to its bitterness and requires rapid disintegration for the preparation of ODT. In this study, ion exchange resin drug complex (IRDC) at three different ratios (1:2, 1:1, 2:1) was prepared using a spray-drying method and then IRDC-loaded ODT containing superdisintegrants (crospovidone, croscarmellose sodium, and sodium starch glycolate) were prepared by the direct compression method. The physical properties and morphologies were then characterized by scanning electron microscopy (SEM), X-ray powder diffraction (PXRD) and electrophoretic laser scattering (ELS), respectively. The in vitro taste-masking efficiency was measured with an electronic tongue (e-Tongue). In vivo bitterness scale was also evaluated by human volunteers and then we defined new term, "bitterness index (BI)" to link in vitro e-Tongue. There was a good correlation of IRDC between in vitro e-Tongue values and in vivo BI. Furthermore, IRDC-loaded ODT showed good in vitro/in vivo correlation in the disintegration time. The optimal IRDC-loaded ODTs displayed similar drug release profiles to the reference tablet (Aricept(®) ODT) in release media of pH 1.2, pH 4.0, pH 6.8 and distilled water but had significantly better palatability in vivo taste-masking evaluation. The current IRDC-loaded ODT according to the in vitro and in vivo correlation of disintegration and bitter taste masking could provide platforms in ODT dosage formulations of donepezil hydrochloride for improved patient compliances. PMID:23933050

Kim, Jong-Il; Cho, Sang-Min; Cui, Jing-Hao; Cao, Qing-Ri; Oh, Euichaul; Lee, Beom-Jin

2013-10-15

99

Comparison of morphine and morphine with ketamine for postoperative analgesia  

Microsoft Academic Search

Purpose  The purpose of this study was to compare morphine with ketamine to morphine alone in a doubleblind investigation of postsurgical\\u000a pain control.\\u000a \\u000a \\u000a \\u000a Methods  Fortytwo ASA 1 and 2 patients undergoing elective microdiscectomy were administered either 1 mg · ml? 1 of morphine (n = 20) or 1 mg · ml? 1 of both morphine and ketamine (n = 22) via iv

Keith B. Javery; Todd W. Ussery; Herbert G. Steger; George W. Colclough

1996-01-01

100

Oral 4-aminosalicylic acid versus 5-aminosalicylic acid slow release tablets. Double blind, controlled pilot study in the maintenance treatment of Crohn's ileocolitis.  

PubMed Central

4-Aminosalicylic acid (4-ASA) has been suggested as an effective treatment for both active and quiescent ulcerative colitis. 5-Aminosalicylic acid (5-ASA) is well accepted for the maintenance treatment of inactive ulcerative colitis. Moreover, recent studies suggest that 5-ASA may also be effective in maintaining remission in Crohn's colitis. As treatment with 4-ASA may result in less side effects, the efficacy of a one year's maintenance treatment with oral 4-ASA (1.5 g/d, slow release tablets, n = 19) and oral 5-ASA (1.5 g/d, slow release tablets, n = 21) was compared in a double blind, randomised trial in patients with quiescent Crohn's ileocolitis. Patients with ileocolonic or colonic involvement were enrolled if in stable remission for more than two months but less than one year. Baseline demography and clinical severity were similar in both groups. Total colonoscopy and ileoscopy were performed at enrollment and at the end of the study. After one year seven of 19 patients receiving 4-ASA (36%) and 8 of 21 receiving 5-ASA (38%) had developed a clinical relapse, as defined by a rise in the Crohn's disease activity index (CDAI) of more than 100 points to values higher than 150. The relapse rates between the 4-ASA and the 5-ASA groups were not statistically different although no comparison with the spontaneous relapse rate in a placebo group could be made. Clinical relapse was accompanied by a statistically significant rise in serum concentrations of soluble interleukin 2 receptor and by an increased percentage of activated peripheral blood T cells. There were no statistical differences between the 4-ASA and the 5-ASA groups regarding the height of rise in CDAI or of soluble interleukin 2 receptor concentrations during relapse, thus showing a similar severity relapsed disease activity. In conclusion, 4-ASA maybe as effective as 5-ASA in the maintenance treatment of quiescent Crohn's disease and there were no differences in the severity of relapse between both treatment groups. PMID:7926910

Schreiber, S; Howaldt, S; Raedler, A

1994-01-01

101

Morphine6Glucuronide: Morphine??s Successor for Postoperative Pain Relief?  

Microsoft Academic Search

In searching for an analgesic with fewer side effects than morphine, examination of morphine's active metabolite, morphine-6-glucuronide (M6G), sug- gests that M6G is possibly such a drug. In contrast to morphine, M6G is not metabolized but excreted via the kidneys and exhibits enterohepatic cycling, as it is a substrate for multidrug resistance transporter pro- teins in the liver and intestines.

Eveline L. A. van Dorp; Raymonda Romberg; Elise Sarton; James G. Bovill; Albert Dahan

2006-01-01

102

Urinary excretion and metabolism of arbutin after oral administration of Arctostaphylos uvae ursi extract as film-coated tablets and aqueous solution in healthy humans.  

PubMed

Bearberry leaves and preparations made from them are traditionally used for urinary tract infections. The urinary excretion of arbutin metabolites was examined in a randomized crossover design in 16 healthy volunteers after the application of a single oral dose of bearberry leaves dry extract (BLDE). There were two groups of application using either film-coated tablets (FCT) or aqueous solution (AS). The urine sample analysis was performed by a validated HPLC coolarray method (hydroquinone) and a validated capillary electrophoresis method (hydroquinone-glucuronide, hydroquinone-sulfate). The total amounts of hydroquinone equivalents excreted in the urine from BLDE were similar in both groups. With FCT, 64.8% of the arbutin dose administered was excreted; with AS, 66.7% was excreted (p = 0.61). The maximum mean urinary concentration of hydroquinone equivalents was a little higher and peaked earlier in the AS group versus the FCT group, although this did not reach statistical significance (Cur max = 1.6893 micromol/ml vs. 1.1250 micromol/ml, p = 0.13; tmax (t midpoint) = 3.60 h vs. 4.40 h, p = 0.38). The relative bioavailability of FCT compared to AS was 103.3% for total hydroquinone equivalents. There was substantial intersubject variability. No significant differences between the two groups were found in the metabolite patterns detected (hydroquinone, hydroquinone-glucuronide, and hydroquinone-sulfate). PMID:12162475

Schindler, Gernot; Patzak, Ulrich; Brinkhaus, Benno; von Niecieck, Alexander; Wittig, Jörg; Krähmer, Nils; Glöckl, Ingmar; Veit, Markus

2002-08-01

103

Simultaneous determination by UPLC-MS/MS of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets: application to a pharmacokinetic study.  

PubMed

A rapid, reliable, and sensitive method was developed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with an electrospray ionization (ESI) source for determination of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets (GBTs). The method simultaneously detects bilobalide (BB), ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC), quercetin (QCT), kaempferol (KMF), and isorhamnetin (ISR) for pharmacokinetic study. The analytes and internal standard (IS) were extracted from rat plasma by acetidin. An MS/MS detection was conducted using multiple reaction monitoring (MRM) and operating in the negative ionization mode. The calibration curve ranges were 5-500, 5-500, 2.5-250, 1-100, 1-100, 1-100, and 1-100 ng/ml for BB, GA, GB, GC, QCT, KMF, and ISR, respectively. The mean recovery of the analytes ranged from 68.11% to 84.42%. The intra- and inter-day precisions were in the range of 2.33%-9.86% and the accuracies were between 87.67% and 108.37%. The method was used successfully in a pharmacokinetic study of GBTs. The pharmacokinetic parameters of seven compounds were analyzed using a non-compartment model. Plasma concentrations of the seven compounds were determined up to 48 h after administration, and their pharmacokinetic parameters were in agreement with previous studies. PMID:25367786

Wang, Wen-ping; Liu, Na; Kang, Qian; Du, Pei-pei; Lan, Yi; Zhao, Bo-chen; Chen, Yan-yan; Zhang, Qing; Li, Hui; Zhang, Ye-wen; Wu, Qing

2014-11-01

104

Simultaneous determination by UPLC-MS/MS of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets: application to a pharmacokinetic study*  

PubMed Central

A rapid, reliable, and sensitive method was developed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with an electrospray ionization (ESI) source for determination of seven bioactive compounds in rat plasma after oral administration of Ginkgo biloba tablets (GBTs). The method simultaneously detects bilobalide (BB), ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC), quercetin (QCT), kaempferol (KMF), and isorhamnetin (ISR) for pharmacokinetic study. The analytes and internal standard (IS) were extracted from rat plasma by acetidin. An MS/MS detection was conducted using multiple reaction monitoring (MRM) and operating in the negative ionization mode. The calibration curve ranges were 5–500, 5–500, 2.5–250, 1–100, 1–100, 1–100, and 1–100 ng/ml for BB, GA, GB, GC, QCT, KMF, and ISR, respectively. The mean recovery of the analytes ranged from 68.11% to 84.42%. The intra- and inter-day precisions were in the range of 2.33%–9.86% and the accuracies were between 87.67% and 108.37%. The method was used successfully in a pharmacokinetic study of GBTs. The pharmacokinetic parameters of seven compounds were analyzed using a non-compartment model. Plasma concentrations of the seven compounds were determined up to 48 h after administration, and their pharmacokinetic parameters were in agreement with previous studies. PMID:25367786

Wang, Wen-ping; Liu, Na; Kang, Qian; Du, Pei-pei; Lan, Yi; Zhao, Bo-chen; Chen, Yan-yan; Zhang, Qing; Li, Hui; Zhang, Ye-wen; Wu, Qing

2014-01-01

105

Double-layered mucoadhesive tablets containing nystatin  

Microsoft Academic Search

The objective of this work was to design a mucoadhesive tablet with a potential use in the treatment of oral candidosis. A\\u000a 2-layered tablet containing nystain was formulated. Lactose CD (direct compression), carbomer (CB), and hydroxypropylmethylcellulose\\u000a (HPMC) were used as excipients. Tablets were obtained through direct compression. Properties such as in vitro mucoadhesion,\\u000a water uptake, front movements, and drug release

Juan Manuel Llabot; Ruben Hilario Manzo; Alberto allemandi

2002-01-01

106

Investigation and analysis of oncologists’ knowledge of morphine usage in cancer pain treatment  

PubMed Central

Purpose To examine oncologists’ knowledge of cancer pain and morphine’s clinical application in the People’s Republic of China. In addition, this study analyzes and discusses the negative factors that currently affect the clinical application of morphine. Patients and methods A questionnaire survey was given to a random sample of 150 oncologists from Tianjin Medical University Cancer Institute and Hospital. The statistical results were analyzed and processed using SPSS version 21.0 and Matlab version 2012a statistical software. Single-factor analysis of variance, Kruskal–Wallis nonparametric test, and independent samples t-test were adopted to analyze the difference in knowledge scores of morphine usage. The study also identified major impediment factors on clinical use of morphine. Results Among the 127 respondents, morphine controlled-release tablets were the most popular drug chosen to treat severe cancer pain (76 respondents, 35.8%). Participants who reported having received training in cancer pain management and drug use demonstrated a significantly higher mean score of basic knowledge compared with their untrained peers (11.51±2.60 versus 9.28±3.68, t=2.48, P=0.022). The top four barriers to widespread clinical use of morphine for cancer pain were 1) insufficient analgesia administration training for medical personnel, 2) poor patient compliance, 3) drug side effects, and 4) concerns surrounding drug addiction. Conclusion The oncologists in the People’s Republic of China simultaneously lack comprehensive knowledge and harbor misconceptions with regard to cancer pain treatment and morphine’s clinical application. Creating professional training initiatives for oncologists is necessary to enhance their awareness and expertise in morphine use for cancer pain treatment. PMID:24876783

Liu, Weiran; Xie, Shumin; Yue, Lin; Liu, Jiahao; Woo, Stephanie Mu-Lian; Liu, Weilin; Miller, Adam R; Zhang, Jing; Huang, Lijun; Zhang, Lei

2014-01-01

107

Sucrose esters with various hydrophilic-lipophilic properties: novel controlled release agents for oral drug delivery matrix tablets prepared by direct compaction.  

PubMed

Sucrose esters (SE) are esters of sucrose and fatty acids with various hydrophilic-lipophilic properties which have attracted interest from being used in pharmaceutical applications. This study aimed to gain insight into the use of SE as controlled release agents for direct compacted matrix tablets. The study focused on the effect of hydrophilic-lipophilic properties on tableting properties and drug release. Sucrose stearate with hydrophilic-lipophilic balance (HLB) values ranging from 0 to 16 was systematically tested. Tablet formulations contained SE, metoprolol tartrate as a highly soluble model drug and dibasic calcium phosphate dihydrate as a tablet formulation filler in the ratio 1:1:2. The compaction behaviour of matrix tablets was compared with the compacts of individual starting materials as reference. SE incorporation improved the plasticity, compressibility and lubricating property of powder mixtures. The hydrophilic-lipophilic properties of SE affected tableting properties, drug release rate and release mechanism. Increasing hydrophilicity corresponding to the increased monoesters in SE composition increased the relative porosity, elastic recovery and tensile strength of the tablets due to the increased hydrogen bonding between the monoesters. This also facilitated the swelling behaviour of SE, which sustained the drug release rate. A sustained release effect prevailed in tablets containing SE with HLB values of 3-16. The ability to improve the tableting properties as well as sustain the drug release rate of the highly soluble model drug via gelation of SE highlights SE as promising controlled release regulators for direct compacted matrix tablets comprising drugs with various solubilities according to the Biopharmaceutics Classification System. PMID:20132913

Chansanroj, K; Betz, G

2010-08-01

108

21 CFR 520.1310 - Marbofloxacin tablets.  

Code of Federal Regulations, 2012 CFR

...CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1310 Marbofloxacin tablets...Indications for use . For the treatment of infections in dogs and cats associated with bacteria susceptible to marbofloxacin....

2012-04-01

109

Taste-masked and affordable donepezil hydrochloride orally disintegrating tablet as promising solution for non-compliance in Alzheimer's disease patients.  

PubMed

Abstract Context: Manufacturing process and superdisintegrants used in orally disintegrating tablet (ODT) formulation are often time discussed. However, the effect of suitable filler for ODT formulation is not explored thoroughly. Objective: The aim of this study was to develop a novel taste masked and affordable donepezil hydrochloride ODT with fast disintegration time and stable to improve medication compliance of Alzheimer's disease patient. Methods and materials: The ODT was manufactured using simple wet-granulation method. Crospovidone XL-10 was used as superdisintegrant and optimization was done by comparing the effect of three grades of lactose monohydrate compound as filler: Starlac®, Flowlac® and Tablettose®. Results and discussion: Formulations containing higher amount of colloidal silicon dioxide showed increase in hardness, weight, disintegration time and wetting time after stability study. Formulation E which containing 50% of Starlac® was found with shortest in vitro disintegration time (21.7?±?1.67?s), in vivo disintegration time (24.0?±?1.05?s) and in vitro disintegration time in artificial salvia (22.5?±?1.67?s). Physical stability studies at 40?°C/75% RH for 6 months, Fourier transform infrared spectroscopy analysis and X-ray diffraction results showed that the formulation was stable. The drug-released profile showed that 80% of donepezil hydrochloride was released within 1?min. A single-dose, fasting, four-period, seven-treatment, double-blinded study involving 16 healthy human volunteers was performed to evaluate the palatability of ODT. Formulation VII containing 10?mg of ammonium glycyrrhizinate was able to mask the bitter taste of the drug. Conclusion: The product has the potential to be commercialized and it might serve as solution for non-compliance among the Alzheimer's disease patients. PMID:24495273

Liew, Kai Bin; Tan, Yvonne Tze Fung; Peh, Kok Khiang

2014-02-01

110

Tablet Weaving  

ERIC Educational Resources Information Center

Article described a weaving technique called tablet weaving, an ancient textile process that provides opportunity for making a variety of items, such as guitar straps, belts, and decorative bands. (Author/RK)

Kren, Margo

1976-01-01

111

Should vitamin B12 tablets be included in more Canadian drug formularies? An economic model of the cost-saving potential from increased utilisation of oral versus intramuscular vitamin B12 maintenance therapy for Alberta seniors  

PubMed Central

Objective The aim of this study was to estimate the cost-savings attainable if all patients aged ?65 years in Alberta, Canada, currently on intramuscular therapy were switched to oral therapy, from the perspective of a provincial ministry of health. Setting Primary care setting in Alberta, Canada. Participants Seniors of age 65 years and older currently receiving intramuscular vitamin B12 therapy. Intervention Oral vitamin B12 therapy at 1000??g/day versus intramuscular therapy at 1000??g/month. Primary and secondary outcome measures Cost saving from oral therapy over intramuscular therapy, from the perspective of the Alberta Ministry of Health, including drug costs, dispensing fees, injection administration fees, additional laboratory monitoring and physician visit fees. Results Over 5?years, if all Albertans aged 65 years and older who currently receive intramuscular B12 are switched to oral therapy, our model found that $C13?975?883 can be saved. Even if no additional physician visits are billed for among patients receiving intramuscular therapy, $C8?444?346 could be saved from reduced administration costs alone. Conclusions Oral B12 therapy has been shown to be an effective therapeutic option for patients with vitamin B12 deficiency, yet only three provinces and the Non-Insured Health Benefits program include oral tablets on their formulary rather than the parenteral preparation. To ensure judicious use of limited health resources, clinicians and formulary committees are encouraged to adopt oral B12 therapy as a clinically and cost-effective first-line therapy for vitamin B12 deficiency. PMID:24793247

Houle, Sherilyn K D; Kolber, Michael R; Chuck, Anderson W

2014-01-01

112

Controlled-release oxycodone compared with controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-group study  

Microsoft Academic Search

Controlled-release oral formulations of oxycodone and morphine are both suitable analgesics for moderate to severe pain. They were compared in cancer-pain patients randomized to double-blind treatment with controlled-release oxycodone (n = 48) or controlled-release morphine (n = 52) every 12 h for up to 12 days. Stable analgesia was achieved by 83% of controlled-release oxycodone and 81% of controlled-release morphine

Patricia Mucci-LoRusso; Barry S. Berman; Peter T. Silberstein; Marc L. Citron; Linda Bressler; Sharon M. Weinstein; Robert F. Kaiko; Barbara J. Buckley; Robert F. Reder

1998-01-01

113

Sensitivity of quantitative sensory models to morphine analgesia in humans  

PubMed Central

Introduction Opioid analgesia can be explored with quantitative sensory testing, but most investigations have used models of phasic pain, and such brief stimuli may be limited in the ability to faithfully simulate natural and clinical painful experiences. Therefore, identification of appropriate experimental pain models is critical for our understanding of opioid effects with the potential to improve treatment. Objectives The aim was to explore and compare various pain models to morphine analgesia in healthy volunteers. Methods The study was a double-blind, randomized, two-way crossover study. Thirty-nine healthy participants were included and received morphine 30 mg (2 mg/mL) as oral solution or placebo. To cover both tonic and phasic stimulations, a comprehensive multi-modal, multi-tissue pain-testing program was performed. Results Tonic experimental pain models were sensitive to morphine analgesia compared to placebo: muscle pressure (F=4.87, P=0.03), bone pressure (F=3.98, P=0.05), rectal pressure (F=4.25, P=0.04), and the cold pressor test (F=25.3, P<0.001). Compared to placebo, morphine increased tolerance to muscle stimulation by 14.07%; bone stimulation by 9.72%; rectal mechanical stimulation by 20.40%, and reduced pain reported during the cold pressor test by 9.14%. In contrast, the more phasic experimental pain models were not sensitive to morphine analgesia: skin heat, rectal electrical stimulation, or rectal heat stimulation (all P>0.05). Conclusion Pain models with deep tonic stimulation including C fiber activation and and/or endogenous pain modulation were more sensitive to morphine analgesia. To avoid false negative results in future studies, we recommend inclusion of reproducible tonic pain models in deep tissues, mimicking clinical pain to a higher degree. PMID:25525384

Olesen, Anne Estrup; Brock, Christina; Sverrisdóttir, Eva; Larsen, Isabelle Myriam; Drewes, Asbjørn Mohr

2014-01-01

114

Kapanol™ capsules : pellet formulation provides alternative methods of administration of sustained-release morphine sulfate.  

PubMed

Novel methods of administration of morphine for the alleviation of pain in terminally ill patients with cancer who are unable to swallow tablets or capsules or eat or drink have been investigated in in vitro studies. The drug-release rate of Kapanol™, a pelletised sustained-release morphine sulfate capsule, was not altered when the pellets were poured onto foodstuffs (including jam, yoghurt, apple sauce and ice-cream) and liquids (orange juice, milk and water). In addition, the drug-release profile of Kapanol™ pellets was not altered when pellets were flushed with water through a 16 French gastrostomy tube. However, the pellets were too large to pass through a 12 French nasogastric tube. Although clinical studies are needed to determine patient acceptance, these data suggest that sprinkling Kapanol™ pellets onto soft food or liquids or through a gastrostomy tube may be recommended as an alternative method of administration of morphine sulfate. PMID:24610669

Jones, R; Hale, E; Talomsin, L; Phillips, R

1996-08-01

115

Role of various natural, synthetic and semi-synthetic polymers on drug release kinetics of losartan potassium oral controlled release tablets  

PubMed Central

Objective: The objective of the present work was to formulate and to characterize controlled release matrix tablets of losartan potassium in order to improve bioavailability and to minimize the frequency of administration and increase the patient compliance. Materials and Methods: Losartan potassium controlled release matrix tablets were prepared by direct compression technique by the use of different natural, synthetic and semisynthetic polymers such as gum copal, gum acacia, hydroxypropyl methyl cellulose K100 (HPMC K100), eudragit RL 100 and carboxy methyl ethyl cellulose (CMEC) individually and also in combination. Studies were carried out to study the influence of type of polymer on drug release rate. All the formulations were subjected to physiochemical characterization such as weight variation, hardness, thickness, friability, drug content, and swelling index. In vitro dissolution studies were carried out simulated gastric fluid (pH 1.2) for first 2 h and followed by simulated intestinal fluid (pH 6.8) up to 24 h, and obtained dissolution data were fitted to in vitro release kinetic equations in order to know the order of kinetics and mechanism of drug release. Results and Discussion: Results of physiochemical characterization of losartan potassium matrix tablets were within acceptable limits. Formulation containing HPMC K100 and CMEC achieved the desired drug release profile up to 24 h followed zero order kinetics, release pattern dominated by Korsmeyer — Peppas model and mechanism of drug release by nonfickian diffusion. The good correlation obtained from Hixson-Crowell model indicates that changes in surface area of the tablet also influences the drug release. Conclusion: Based on the results, losartan potassium controlled release matrix tablets prepared by employing HPMC K100 and CMEC can attain the desired drug release up to 24 h, which results in maintaining steady state concentration and improving bioavailability. PMID:25426439

Jayasree, J.; Sivaneswari, S.; Hemalatha, G.; Preethi, N.; Mounika, B.; Murthy, S. Vasudeva

2014-01-01

116

Enantioselective HPLC-DAD method for the determination of etodolac enantiomers in tablets, human plasma and application to comparative pharmacokinetic study of both enantiomers after a single oral dose to twelve healthy volunteers.  

PubMed

An enantioselective high performance liquid chromatographic method with diode array detection (HPLC-DAD) was developed and validated for the determination of etodolac enantiomers in tablets and human plasma. Enantiomeric separation was achieved on a Kromasil Cellucoat chiral column (250 mm × 4.6mm i.d., 5 µm particle size) using a mobile phase consisting of hexane: isopropanol: triflouroacetic acid (90:10:0.1 v/v/v) at a flow rate of 1.0 mL min(-1). The chromatographic system enables the separation of the two enantiomers and the internal standard within a cycle time of 8 min. The resolution between the two enantiomers was 4.25 and the resolution between each enantiomer and the internal standard was more than 2.0. Detection was carried out at 274 nm, and the purity assessment was performed using a photodiode array detector. Solid phase extraction technique using C-18 cartridge was applied to extract the analytes from the plasma samples, and the percentage recovery was more than 95% for the lower quantification limit. The method has been validated with respect to selectivity, linearity, accuracy and precision, robustness, limit of detection and limit of quantification. The validation acceptance criteria were met in all cases. The linearity range for the determination of each enantiomer in human plasma was 0.4-30.0 µg mL(-1) and the limits of quantification of R-etodolac and S-etodolac were 0.20 and 0.19 µg mL(-1), respectively. The validated method was successfully applied to the determination of etodolac enantiomers in tablets and to a comparative pharmacokinetic study of the two enantiomers after the administration of 300 mg single oral dose etodolac racemate tablets to twelve healthy volunteers. PMID:25159440

Hewala, Ismail I; Moneeb, Marwa S; Elmongy, Hatem A; Wahbi, Abdel-Aziz M

2014-12-01

117

Esophageal candidiasis in AIDS. Successful therapy with clotrimazole vaginal tablets taken by mouth.  

PubMed

In this paper we describe the results of oral therapy of esophageal candidiasis with clotrimazole vaginal tablets in 25 homosexual men with AIDS, of whom 19 had oral candidiasis and 16 had esophageal symptoms. Therapy with clotrimazole vaginal tablets, 100 mg, taken by mouth cleared the esophageal symptoms, oral candidiasis, and esophageal lesions completely in all 25 men. Clotrimazole vaginal tablets are a useful alternative to other antifungal agents for the treatment of esophageal candidiasis in AIDS patients. PMID:1995261

Lalor, E; Rabeneck, L

1991-03-01

118

Acute Administration of Pioglitazone Attenuates Morphine Withdrawal Syndrome in Rat: A Novel Role of Pioglitazone.  

PubMed

Long-term exposure to opiates such is morphine induces dependence.The purpose of the present study was to investigate the effects of the acute administration of pioglitazone, a selective agonist of peroxisome proliferator activated receptors gamma (PPAR-?), on the morphine withdrawal syndrome in the rat.Male Wistar rats (200-250?g) were selected randomly and divided into 8 groups including 2 non-dependent groups and 6 morphine-dependent groups which were received additive doses of morphine subcutaneously at an interval of 12?h for 9 continuous days. On the ninth day, only the morning dose of morphine was injected and 2?h later, morphine withdrawal was precipitated by naloxone and then ten distinct withdrawal behaviors were recorded for 45?min. Pioglitazone (5, 10, 20 and 40?mg/kg) was gavaged 2?h before naloxone injection. It is worth noting that 1?h before the pioglitazone (40?mg/kg) gavage, GW-9662 (2?mg/kg), a selective PPAR-? antagonist, was administrated in order to evaluate the possible role of the PPAR-?.The results of this study showed that administration of pioglitazone (40?mg/kg) decreased all withdrawal signs and the statistical analysis indicated that pioglitazone could attenuate the total withdrawal scores significantly. Administration of GW-9662 had no significant effect on pioglitazone attenuation effect on morphine withdrawal symptoms.Taking together, it was concluded that acute oral administration of pioglitazone prevented naloxone-precipitated withdrawal symptoms and GW-9662 could not revert its effect on morphine withdrawal syndrome. It seems that pioglitazone suppresses morphine withdrawal syndrome through PPAR-? independent mechanisms. PMID:24504689

Ghavimi, H; Azarfardian, A; Maleki-Dizaji, N; Hassanzadeh, K; Ghanbarzadeh, S; Charkhpour, M

2014-02-01

119

Pharmaceutical equivalence of metformin tablets with various binders  

Microsoft Academic Search

Metformin hydrochloride is a high-dose drug widely used as an oral anti-hyperglycemic agent. As it is highly crystalline and has poor compaction properties, it is difficult to form tablets by direct compression. The aim of this study was to develop adequate metformin tablets, pharmaceutically equivalent to the reference product, Glucophage® (marketed as Glifage® in Brazil). Metformin 500mg tablets were produced

Tania Mari

120

Miconazole mucoadhesive buccal tablet in high-dose therapy with autologous stem cell transplantation (HDT/ASCT)-induced mucositis.  

PubMed

Oral mucositis is a major cause of morbidity in high-dose therapy/autologous stem cell transplantation (HDT/ASCT), where microbial colonization has an important pathological implication. In this study, we evaluated the impact of miconazole mucoadhesive buccal tablet (MBT) on mucositis-related complications. During two consecutive 34-month periods, patients treated with HDT/ASCT in our hematology department received either miconazole MBT (60 patients) or conventional oral amphotericin B suspensions three times a day (44 patients) in order to prevent or decrease chemotherapy-induced mucositis. The use of miconazole MBT is associated with less infectious complications as indicated by shorter antibiotic use (7.8 vs. 12.3 days; p?morphine use) were in favor of miconazole MBT in patients with multiple myeloma (MM) but not for those with lymphoma. This study suggests that miconazole MBT provides a valid alternative to oral amphotericin B suspensions in regards to mucositis-related complications. A prospective and randomized study is warranted to establish the definite role of miconazole MBT. PMID:25084742

Orvain, C; Moles-Moreau, M P; François, S; Mercier, M; Moal, F; Hamel, J F; Parot-Schinkel, E; Ifrah, N; Hunault-Berger, M; Tanguy-Schmidt, A

2014-08-01

121

Morphine Induces Splenocyte Trafficking into the CNS  

PubMed Central

Opioids significantly alter functional responses of lymphocytes following activation. Morphine, an opioid derivative, alters the Th1 to Th2 response and modulates functional responses such as cytolytic activity and proliferation. Although there has been extensive research involving morphine’s effects on lymphocytes, little is known about the effects morphine has on lymphocyte trafficking. The objective of the study was to use in vivo bioluminescent imaging to determine morphine’s effect on the trafficking pattern of splenocytes systemically and into the CNS following a neuroinflammatory stimulus. A neuroinflammatory response was induced by intracerebrally administering a DNA plasmid producing IFN-? in morphine-dependent or placebo wildtype mice. Mice with or without a neurostimulus received adoptively transferred firefly luciferase transgenic splenocytes and were imaged using a charge-coupled device camera. Morphine dependence significantly altered the inherent ability of splenocytes to traffic into the spleen, and lead to non-directed chaotic trafficking throughout the animal, including the CNS. The morphine-mediated effects on trafficking were blocked by naltrexone. Morphine dependence intensified splenocyte infiltration into the CNS following neuroinflammation induced by IFN-? gene transfer. The study determined that morphine severely altered the ability of non-activated splenocytes to home to the spleen, inducing chaotic extrasplenic trafficking thoughout the animals. Following a neuroinflammatory response, morphine exacerbated infiltration into the CNS. PMID:21858458

Olin, Michael R; Oh, Seunguk; Roy, Sabita; Peterson, Phillip K; Molitor, Thomas

2013-01-01

122

Evaluation of menstrual cycle effects on morphine and pentazocine analgesia  

PubMed Central

Studies have demonstrated menstrual cycle influences on basal pain perception, but direct evidence of menstrual cycle influences on analgesic responses has not been reported in humans. Our aim was to determine whether the magnitude of morphine and pentazocine analgesia varied across the menstrual cycle. Sixty-five healthy women, 35 taking oral contraceptives (OC) and 30 normally cycling (NOC), underwent experimental pain assessment both before and after intravenous administration morphine (0.08 mg/kg) or pentazocine (0.5 mg/kg) compared to saline placebo. Both active drug and placebo were administered once during the follicular phase and once during the luteal phase. Measures of heat, ischemic and pressure pain sensitivity were obtained before and after drug administration. Change scores in pain responses were computed to determine morphine and pentazocine analgesic responses, and medication side effects were recorded. The data were analyzed using mixed-model ANOVAs. NOC women showed slightly greater heat pain sensitivity in the follicular vs. luteal phase, while the reverse pattern emerged for OC women (p=0.046). Also, OC women showed lower pressure pain thresholds compared to NOC women (p < .05). Regarding analgesic responses, NOC women showed greater morphine analgesia for ischemic pain during the follicular vs. the luteal phase (p=0.004). Likewise, side effects for morphine were significantly higher in NOC women in the follicular phase than in the luteal phase (p=0.02). These findings suggest that sex hormones may influence opioid responses; however, the effects vary across medications and pain modalities and are likely to be modest in magnitude. PMID:21239109

Ribeiro-Dasilva, MC; Shinal, RM; Glover, T; Williams, RS; Staud, R; Riley, JL; Fillingim, RB

2011-01-01

123

Miconazole mucoadhesive tablet for oropharyngeal candidiasis  

PubMed Central

Oropharyngeal candidiasis is a commonly encountered problem in daily clinical practice. Topical therapies for oropharyngeal candidiasis are considered preferable to systemic therapies in most patient populations. However, traditional topical therapies have limitations including short contact time with the oral mucosa and the need for multiple doses each day. Miconazole mucoadhesive tablet has recently been approved in Europe (Loramyc®) and the USA (Oravig™) for the treatment of oropharyngeal candidiasis. This tablet adheres to the oral mucosa and provides sustained local release of miconazole over a period of several hours with just one daily application. This article reviews the pharmacology, safety and efficacy of this novel agent. PMID:21171872

Lalla, Rajesh V; Bensadoun, René-Jean

2011-01-01

124

Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia  

PubMed Central

Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation. PMID:18706994

Hutchinson, Mark R.; Northcutt, Alexis L.; Chao, Lindsey W.; Kearney, Jeffrey J.; Zhang, Yingning; Berkelhammer, Debra L.; Loram, Lisa C.; Rozeske, Robert R.; Bland, Sondra T.; Maier, Steven F.; Gleeson, Todd T.; Watkins, Linda R.

2008-01-01

125

21 CFR 520.763a - Dithiazanine iodide tablets.  

Code of Federal Regulations, 2013 CFR

...1) The tablets are administered orally to dogs immediately after feeding using the following dosage schedule for various parasite infestations: Milligrams per pound of body weight Length of treatment—days Large roundworms (Toxocara canis,...

2013-04-01

126

21 CFR 520.763a - Dithiazanine iodide tablets.  

...1) The tablets are administered orally to dogs immediately after feeding using the following dosage schedule for various parasite infestations: Milligrams per pound of body weight Length of treatment—days Large roundworms (Toxocara canis,...

2014-04-01

127

21 CFR 520.2362 - Thenium closylate tablets.  

Code of Federal Regulations, 2012 CFR

...1) The tablets are administered orally to dogs as a single day treatment of canine ancylostomiasis by the removal from the intestines of the adult forms of the species Ancylostoma caninum and Uncinaria stenocephala (hookworms). Dogs weighing...

2012-04-01

128

Improvement in oral chronic graft-versus-host disease with the administration of effervescent tablets of topical budesonide-an open, randomized, multicenter study.  

PubMed

Chronic graft-versus-host disease (cGVHD) frequently involves oral tissues. Although the mucosal changes may be painful and impair oral function, there is currently no topical therapy available for oral cGVHD that has been proven to work in an evidence-based manner. The aims of this study were to (1) assess the response of patients with oral cGVHD to various doses of a new topical budesonide formulation; (2) evaluate the efficacy and safety of the new topical budesonide formulation in these patients. An open, randomized, multicenter phase II pilot study with 4 treatment arms differing in application frequency and duration was performed. Response to treatment was scored by the clinician and patient using several scales. Oral cGVHD improved in all patients, with a median reduction of 70%. Pain reduction was similar in all study arms. The rate of objective improvement (defined as ?50%) was not significantly different among the 4 study arms. The safety profile was satisfactory. Topical budesonide mouthwash (3 mg/10 mL) improved oral cGVHD in all patients when applied for 5 or 10 minutes, 2 or 3 times daily. The response was similar in all treatment arms. Safety analysis supported a dosing schedule of 3 mg of budesonide 3 times a day for 10 minutes. PMID:21703973

Elad, Sharon; Zeevi, Itai; Finke, Jürgen; Koldehoff, Michael; Schwerdtfeger, Rainer; Wolff, Daniel; Mohrbacher, Ralf; Levitt, Michael; Greinwald, Roland; Shapira, Michael Y

2012-01-01

129

MTN-001: Randomized Pharmacokinetic Cross-Over Study Comparing Tenofovir Vaginal Gel and Oral Tablets in Vaginal Tissue and Other Compartments  

PubMed Central

Background Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development. Objective MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design. Methods and Findings We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ?90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ?130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03). Conclusions Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir’s antiviral effect substantially influence PrEP efficacy. Trial Registration ClinicalTrials.gov NCT00592124 PMID:23383037

Hendrix, Craig W.; Chen, Beatrice A.; Guddera, Vijayanand; Hoesley, Craig; Justman, Jessica; Nakabiito, Clemensia; Salata, Robert; Soto-Torres, Lydia; Patterson, Karen; Minnis, Alexandra M.; Gandham, Sharavi; Gomez, Kailazarid; Richardson, Barbra A.; Bumpus, Namandje N.

2013-01-01

130

21 CFR 520.1616 - Orbifloxacin tablets.  

Code of Federal Regulations, 2011 CFR

...CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1616 Orbifloxacin tablets...c) of this chapter. (c) Conditions of use in dogs and cats —(1) Amount . 2.5 to 7.5 mg per kilogram body...

2011-04-01

131

21 CFR 520.1900 - Primidone tablets.  

Code of Federal Regulations, 2011 CFR

...CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1900 Primidone tablets...species, as primidone appears to have a specific neurotoxicity in cats. Federal law restricts this drug to use by or on the order...

2011-04-01

132

A paper-based lateral flow assay for morphine.  

PubMed

Morphine was used as a model analyte to examine the possibility of using cellulose, physically modified by papermaking and converting techniques, as a capillary matrix in a lateral flow type of diagnostic assay. This research was directed toward low-cost, disposable, and portable paper-based diagnostics, with the aim of addressing the analytical performance of paper as a substrate in the analysis for drugs of abuse. Antibody Fab fragments were used as sensing molecules, and gold nanoparticle detection was employed. Inkjet printing was used to pattern sensing biomolecules as detection zones on paper. To validate the usefulness of paper as a diagnostic platform, the principle of a direct sandwich assay, based on immunocomplex formation between morphine and the anti-morphine Fab fragment and detection of the formed immunocomplex by another Fab fragment, was implemented. Results were compared with that achieved by using nitrocellulose as a reference material. Possible interfering from the sample matrix on assay quality was investigated with spiked oral fluid samples. Under optimized conditions, a visually assessed limit of detection for the sandwich assay was 1 ng/mL, indicating that the paper-based test devices developed in this work can perform screening for drugs of abuse and can fulfill the requirement for a sensitive assay in diagnostically relevant ranges. PMID:25023970

Teerinen, Tuija; Lappalainen, Timo; Erho, Tomi

2014-09-01

133

Attenuation of morphine analgesic tolerance by rosuvastatin in naïve and morphine tolerance rats.  

PubMed

Recent studies suggested that statins have anti-inflammatory effects beyond their lipid-lowering properties. Since inflammation in the central nervous system was highly related to morphine tolerance, we sought to investigate whether statins could affect morphine tolerance by mediating glia-derived proinflammatory cytokines secretion. We have undertaken two separate studies: Firstly, we determined the effect of rosuvastatin on naïve rats during induction of morphine tolerance. Secondly, we investigated whether rosuvastation could attenuate the morphine analgesic tolerance in rats that the morphine tolerance established previously. Results demonstrated that peroral rosuvastatin not only delays, but also partially reverses the tolerance to morphine analgesia in rats. The administration of rosuvastatin during induction of morphine tolerance attenuated the activation of ERK and the release of proinflammatory cytokines in the lumbar spinal cord. Similar outcomes were observed in rats were morphine tolerance was established previously. Moreover, our study also found that repeated administration of morphine could activate the astrocytes in the spinal cord while rosuvastation succeeds in suppressing the activation of astrocytes. Our results support the idea that targeting glia-derived proinflammatory effects during morphine treatment is a novel and clinically promising method for enhancing analgesic effects of morphine. We identify a potential new application of statins in the treatment of morphine analgesic tolerance. PMID:25261133

Li, Yongle; Shu, Yinyin; Ji, Qing; Liu, Jian; He, Xiaoyun; Li, Weiyan

2015-02-01

134

Redesign of a Dioxygenase in Morphine Biosynthesis  

E-print Network

Opium poppy (Papaver somniferum) produces medicinally important benzylisoquinoline alkaloids, including the analgesics codeine and morphine, in the morphinan pathway. We aligned three dioxygenases that were recently ...

Runguphan, Weerawat

135

Low-dose oral immunization with lyophilized tissue of herbicide-resistant lettuce expressing hepatitis B surface antigen for prototype plant-derived vaccine tablet formulation  

Microsoft Academic Search

Efficient immunization against hepatitis B virus (HBV) and other pathogens with plant-based oral vaccines requires appropriate plant expressors and the optimization of vaccine compositions and administration protocols. Previous immunization studies were mainly based on a combination of the injection of a small surface antigen of HBV (S-HBsAg) and the feeding with raw tissue contain- ing the antigen, supplemented with an

Tomasz Pniewski; Józef Kapusta; Piotr Boci?g; Jacek Wojciechowicz; Anna Kostrzak; Micha? Gdula; Olga Fedorowicz-Stro?ska; Piotr Wójcik; Halina Otta; S?awomir Samardakiewicz; Bogdan Wolko; Andrzej P?ucienniczak

2011-01-01

136

Delayed-Release Oral Mesalamine at 4.8 g\\/day (800 mg tablet) for the Treatment of Moderately Active Ulcerative Colitis: The ASCEND II Trial  

Microsoft Academic Search

BACKGROUND AND AIMS:Preliminary data have shown that delayed release oral mesalamine (Asacol®) dosed at 4.8 g\\/day provided additional efficacy benefit compared to 1.6 g\\/day in patients with mildly to moderately active ulcerative colitis. Additionally, Asacol dosed at 2.4 g\\/day has been proved to be more effective than 1.6 g\\/day. Whether 4.8 g\\/day of mesalamine (dosed with an investigational 800 mg

Stephen B. Hanauer; William J. Sandborn; Asher Kornbluth; Seymour Katz; Michael Safdi; Scott Woogen; Gino Regalli; Chyon Yeh; Nancy Smith-Hall; Funmilay Ajayi

2005-01-01

137

Chemical characterization with XPS of the surface of polymer microparticles loaded with morphine.  

PubMed

Hydrophilic matrices are a potentially useful option for the development of oral controlled-release formulations. The porous surface of these particles makes it possible to control or modify release of the active principle after administration. As a result, such formulations can be used in liquid controlled-release pharmaceutical formulations. We investigated a method of spontaneous drug encapsulation to prepare ethylcellulose polymer microparticles (since the polymer is synthetic rather than natural the final suspension is called pseudolatex) filled with morphine hydrochloride. Morphine is incorporated to water during the synthesis process and thus it is microencapsulated inside the micelles that give rise to the final microparticles. X-ray photoelectron spectroscopy (XPS), a technique that can identify elements in a sample without destroying it, was used for the chemical analysis of the surface of these microspheres. The results demonstrated the complete absence of morphine from the microsphere surface, which was taken as evidence that the drug had been completely encapsulated. PMID:17074455

Morales, M E; Ruiz, M A; Oliva, I; Oliva, M; Gallardo, V

2007-03-21

138

Morphine versus remifentanil for intubating preterm neonates  

PubMed Central

A double?blind, randomised controlled study was conducted to evaluate the intubation conditions in 20 preterm neonates following the use of either morphine or remifentanil as premedication. The findings suggest that the overall intubation conditions were significantly better (p?=?0.0034) in the remifentanil group than in the morphine group. No severe complications were observed in either group. PMID:17074784

e Silva, Yerkes Pereira; Gomez, Renato Santiago; de Oliveira Marcatto, Juliana; Maximo, Thadeu Alves; Barbosa, Rosilu Ferreira

2007-01-01

139

Intravenous morphine pharmacokinetics in pediatric patients with sickle cell disease  

Microsoft Academic Search

To examine the pharmacokinetics of parenteral opioids, such as morphine, in patients with sickle cell disease, we determined the plasma morphine clearances in 18 patients (aged 6 to 19 years) who were receiving continuous intravenous infusions, and the pharmacokinetics of morphine in an additional six patients after single intravenous doses. Plasma morphine clearances ranged from 6.2 to 59.1 ml min-

Carlton D. Dampier; B. N. Y. Setty; Joann Logan; Jacqueline G. Ioli; Roger Dean

1995-01-01

140

Control of morphine-withdrawal hypothermia by conditional stimuli  

Microsoft Academic Search

Male rats were given increasing doses of morphine sulfate to cause addiction. Each injection was paired with a bell. After a number of pairings, the bell acquired conditional-stimulus property in that, like morphine, it prevented withdrawal hypothermia during 72 h of withholding morphine. In another group the withdrawal hypothermia was precipitated by withholding of morphine injections. The bell reversed that

Mark Roffman; Cherjerla Reddy; Harbans Lal

1973-01-01

141

Stable polymorph of morphine1  

PubMed Central

In the stable polymorph of the title compound, C17H19NO3 [systematic name: (5?,6?)-7,8-didehydro-4,5-ep­oxy-17-methyl­morphinan-3,6-diol], the mol­ecular conformation is in agreement with the characteristics of previously reported morphine forms. The molecule displays the typical T-shape and its piperidine ring adopts a slightly distorted chair conformation. Inter­molecular O—H?O hydrogen bonds link the mol­ecules into helical chains parallel to the b axis. Intra­molecular O—H?O hydrogen bonds are also observed. PMID:23476407

Gelbrich, Thomas; Braun, Doris E.; Griesser, Ulrich J.

2013-01-01

142

Novel approach of aceclofenac fast dissolving tablet.  

PubMed

Fast disintegrating tablets (FDTs) have received ever increasing demand during the last decade, and the ?eld has become a hastily growing area in the pharmaceutical industry. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. Aceclofenac, an NSAID, has been recommended orally for the treatment of bone and connective tissue disorder and thus the formulation of the same resulted in development of several FDT technologies. The present aim is to formulate a tablet which disintegrate and dissolve rapidly and give its rapid onset of action: analgesic, antipyretic and anti-inflammatory action. Besides, the conventional tablets also show poor patient compliance an attempt had been made to formulate for FDT of aceclofenac by using various super disintegrants like sodium starch glycolate, croscarmellose sodium and crosspovidone (polyplasdone XL) and PEG 6000 followed by novel technique. The tablets were evaluated for friability, hardness, weight variation, disintegration time, wetting time, in vitro dissolution studies and drug content studies. It was concluded that the batch which was prepared by using combination of crosspovidone and sodium starch glycolate as a super disintegrant shows excellent disintegration time, enhance dissolution rate, taste masking and hence lead to improve efficacy and bioavailability of drug. PMID:25553683

Dave, Vivek; Yadav, Sachdev; Sharma, Swapnil; Vishwakarma, Pushpendra; Ali, Nasir

2015-01-01

143

Photoaffinity labeling of opioid receptor with morphine-7,8-oxide (morphine epoxide)  

SciTech Connect

The opioid receptor mediating inhibitory action of morphine in the electrically stimulated guinea pig ileum was irreversibly photoinactivated by morphine epoxide (3 X 10(-6) M). Morphine epoxide (up to 3 X 10(-5) M) did not influence the responses of rat vas deferens (epsilon-receptor) or rabbit vas deferens (kappa-receptor) to electrical stimulation. Effective concentrations of morphine epoxide were much lower in the guinea pig ileum (mu-receptor) than in the mouse vas deference (delta-receptor). The inhibitory action of (Met)-enkephalin on the twitch responses of the rat vas deferens and mouse vas deferens to electrical stimulation were not influenced after irradiation in the presence of morphine epoxide (3 X 10(-6) M). Therefore, morphine epoxide is probably a useful probe for photoaffinity labeling of the mu-receptor in vitro.

Takayanagi, I.; Shibata, R.; Miyata, N.; Hirobe, M.

1982-05-01

144

Chronic morphine drinking establishes morphine tolerance, but not addiction in Wistar rats  

Microsoft Academic Search

Objective  Some animal models apply morphine in the drinking water to generate addiction, but related reports are not free of conflicting\\u000a results. Accordingly, this study aimed to figure out if chronic consumption of morphine in the drinking water can induce morphine\\u000a addiction in Wistar rats.\\u000a \\u000a \\u000a \\u000a Methods  For 3 weeks, the animals received a daily morphine dose of 35 mg\\/kg by offering a

Ralf Binsack; Ming-lan Zheng; Zhan-sai Zhang; Liu Yang; Yong-ping Zhu

2006-01-01

145

Intrathecal PLC(?3) oligodeoxynucleotides antisense potentiates acute morphine efficacy and attenuates chronic morphine tolerance.  

PubMed

Morphine is a mainstay for chronic pain treatment, but its efficacy has been hampered by physical tolerance. The underlying mechanism for chronic morphine induced tolerance is complicated and not well understood. PLC(?3) is regarded as an important factor in the morphine tolerance signal pathway. In this study, we determined intrathecal (i.t.) administration of an antisense oligodeoxynucleotide (ODN) of PLC(?3) could quicken the on-set antinociceptive efficacy of acute morphine treatment and prolong the maximum effect up to 4h. The antisense could also attenuate the development of morphine-induced tolerance and left shift the ED50 after 7 day of coadministration with morphine. These results probably were contributed by the PLC(?3) antisense ODN as they successfully knocked down protein expression levels and reduced activity of PLC(?3) in spinal cord in rats. The mismatch group had no such effects. The results confirmed the important involvement of PLC(?3) in both acute morphine efficacy and chronic morphine tolerance at spinal level in rats. This study may provide an idea for producing a novel adjuvant for morphine treatment. PMID:22771399

Quanhong, Zhou; Ying, Xue; Moxi, Chen; Tao, Xu; Jing, Wang; Xin, Zhang; Li, Wang; Derong, Cui; Xiaoli, Zhang; Wei, Jiang

2012-09-01

146

Morphine and codeine concentrations in human urine following controlled poppy seeds administration of known opiate content.  

PubMed

Opiates are an important component for drug testing due to their high abuse potential. Proper urine opiate interpretation includes ruling out poppy seed ingestion; however, detailed elimination studies after controlled poppy seed administration with known morphine and codeine doses are not available. Therefore, we investigated urine opiate pharmacokinetics after controlled oral administration of uncooked poppy seeds with known morphine and codeine content. Participants were administered two 45 g oral poppy seed doses 8 h apart, each containing 15.7 mg morphine and 3mg codeine. Urine was collected ad libitum up to 32 h after the first dose. Specimens were analyzed with the Roche Opiates II immunoassay at 2000 and 300 ?g/L cutoffs, and the ThermoFisher CEDIA(®) heroin metabolite (6-acetylmorphine, 6-AM) and Lin-Zhi 6-AM immunoassays with 10 ?g/L cutoffs to determine if poppy seed ingestion could produce positive results in these heroin marker assays. In addition, all specimens were quantified for morphine and codeine by GC/MS. Participants (N=22) provided 391 urine specimens over 32 h following dosing; 26.6% and 83.4% were positive for morphine at 2000 and 300 ?g/L GC/MS cutoffs, respectively. For the 19 subjects who completed the study, morphine concentrations ranged from <300 to 7522 ?g/L with a median peak concentration of 5239 ?g/L. The median first morphine-positive urine sample at 2000 ?g/L cutoff concentration occurred at 6.6 h (1.2-12.1), with the last positive from 2.6 to 18 h after the second dose. No specimens were positive for codeine at a cutoff concentration of 2000 ?g/L, but 20.2% exceeded 300 ?g/L, with peak concentrations of 658 ?g/L (284-1540). The Roche Opiates II immunoassay had efficiencies greater than 96% for the 2000 and 300 ?g/L cutoffs. The CEDIA 6-AM immunoassay had a specificity of 91%, while the Lin-Zhi assay had no false positive results. These data provide valuable information for interpreting urine opiate results. PMID:24887324

Smith, Michael L; Nichols, Daniel C; Underwood, Paula; Fuller, Zachary; Moser, Matthew A; LoDico, Charles; Gorelick, David A; Newmeyer, Matthew N; Concheiro, Marta; Huestis, Marilyn A

2014-08-01

147

A morphine conjugate vaccine attenuates the behavioral effects of morphine in rats  

PubMed Central

Vaccines for opioid dependence may provide a treatment that would reduce or slow the distribution of the drug to brain, thus reducing the drug's reinforcing effects. We tested whether a conjugate vaccine against morphine (keyhole limpet hemocyanin-6-succinylmorphine; KLH-6-SM) administered to rats would produce antibodies and show specificity for morphine or other heroin metabolites. The functional effects of the vaccine were tested with antinociceptive and conditioned place preference (CPP) tests. Rats were either vaccinated with KLH-6-SM and received two boosts 3 and 16 weeks later or served as controls and received KLH alone. Anti-morphine antibodies were produced in vaccinated rats; levels increased and were sustained at moderate levels through 24 weeks. Antibody binding was inhibited by free morphine and other heroin metabolites as demonstrated by competitive inhibition ELISA. Vaccinated rats showed reduced morphine CPP, tested during weeks 4 to 6, and decreased antinociceptive responses to morphine, tested at week 7. Brain morphine levels, assessed using gas-chromatography coupled to mass spectrometry (GC–MS) on samples obtained at 26 weeks, were significantly lower in vaccinated rats. This suggests that morphine entry into the brain was reduced or slowed. These results provide support for KLH-6-SM as a candidate vaccine for opioid dependence. PMID:23739535

Kosten, Therese A.; Shen, Xiaoyun Y.; O'Malley, Patrick W.; Kinsey, Berma M.; Lykissa, Ernest D.; Orson, Frank M.; Kosten, Thomas R.

2013-01-01

148

Comparison of Echinacea alkylamide pharmacokinetics between liquid and tablet preparations.  

PubMed

The relative oral bioavailability of alkylamides from two different Echinacea dosage forms (liquid and tablet) were compared in a small two-way crossover study in humans (n=3). The liquid preparation investigated contained a mixture of Echinacea purpurea root (300 mg/ml) and Echinacea angustifolia root (200 mg/ml) extracted in 60% ethanol. The tablet preparation investigated was also a mixture of E. purpurea root (675 mg/tablet) and E. angustifolia root (600 mg/tablet), but was prepared from the dried 60% ethanolic extracts of these two Echinacea species. Alkylamides were found to be rapidly absorbed and measurable in plasma from both preparations. No significant differences in the tetraene alkylamide pharmacokinetic parameters for T(1/2), AUC(t-lin) and C(max) in the two different preparations were found. T(max) increased from 20 min for the liquid to 30 min for the tablet, which is not unexpected as the tablet required time for disintegration before absorption could occur. These results suggested that there was no significant difference in the bioavailability of alkylamides from the liquid and tablet Echinacea formulations. Furthermore, the results also indicated that the absorption site and any alkylamide loss due to digestive processes were similar in both preparations. PMID:17289362

Matthias, A; Addison, R S; Agnew, L L; Bone, K M; Watson, K; Lehmann, R P

2007-09-01

149

21 CFR 862.3640 - Morphine test system.  

Code of Federal Regulations, 2012 CFR

...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3640 Morphine test system. (a) Identification. A morphine...

2012-04-01

150

21 CFR 862.3640 - Morphine test system.  

Code of Federal Regulations, 2011 CFR

...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3640 Morphine test system. (a) Identification. A morphine...

2011-04-01

151

21 CFR 862.3640 - Morphine test system.  

Code of Federal Regulations, 2010 CFR

...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3640 Morphine test system. (a) Identification. A morphine...

2010-04-01

152

21 CFR 862.3640 - Morphine test system.  

Code of Federal Regulations, 2013 CFR

...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3640 Morphine test system. (a) Identification. A morphine...

2013-04-01

153

21 CFR 862.3640 - Morphine test system.  

...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3640 Morphine test system. (a) Identification. A morphine...

2014-04-01

154

Characterization of Morphine Self-Administration Following Spinal Cord Injury  

E-print Network

spinal injury. These experiments used a clinically relevant self-administration paradigm to examine both addiction and functional recovery after morphine administration. To assess morphine administration in the acute phase of SCI, animals were placed...

Woller, Sarah Ann

2013-07-16

155

Dextromethorphan potentiates morphine antinociception at the spinal level in rats  

Microsoft Academic Search

Purpose  Morphine is an effective analgesic, but adverse effects limit its clinical use in higher doses. The non-opioid antitussive,\\u000a dextromethorphan (DM), can potentiate the analgesic effect of morphine and decrease the dose of morphine in acute postoperative\\u000a pain, but the underlying mechanism remains unclear. We previously observed that DM increases the serum concentration of morphine\\u000a in rats. Therefore, we investigated the

Lok-Hi Chow; Eagle Y.-K. Huang; Shung-Tai Ho; Tak-Yu Lee; Pao-Luh Tao

2004-01-01

156

A Bacoside containing Bacopa monnieri extract reduces both morphine hyperactivity plus the elevated striatal dopamine and serotonin turnover.  

PubMed

Bacopa monnieri (BM) has been used in Ayurvedic medicine as a nootropic, anxiolytic, antiepileptic and antidepressant. An n-butanol extract of the plant (nBt-ext BM) was analysed and found to contain Bacoside A (Bacoside A3, Bacopaside II and Bacopasaponin C). The effects of the BM extract were then studied on morphine-induced hyperactivity as well as dopamine and serotonin turnover in the striatum since these parameters have a role in opioid sensitivity and dependence. Mice were pretreated with saline or nBt-ext BM (5, 10 and 15 mg/kg, orally), 60 min before morphine administration and locomotor activity was subsequently recorded. Immediately after testing, striatal tissues were analysed for dopamine (DA), serotonin (5HT) and their metabolites using HPLC coupled with electrochemical detection. The results indicated that nBt-ext BM significantly (p < 0.001) decreased locomotor activity in both the saline and morphine treated groups. Additionally, nBt-ext BM significantly lowered morphine-induced dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-H1AA) upsurges in the striatum but failed to affect DA, 5-HT and their metabolites in the saline treated group. These findings suggest that nBt-ext BM has an antidopaminergic/serotonergic effect and may have potential beneficial effects in the treatment of morphine dependence. PMID:22105846

Rauf, Khalid; Subhan, Fazal; Sewell, Robert D E

2012-05-01

157

Biopharmaceutical evaluation of new slow release tablets obtained by hot tableting of coated pellets with tramadol hydrochloride.  

PubMed

This study was aimed at a biopharmaceutical evaluation of a new oral dosage form of tramadol hydrochloride (TH)--slow release tablets obtained by hot tableting of coated pellets, 100 mg (TP), compared to the conventional slow release tablets, Tramal Retard, 100 mg (TR). Both TP and TR formulations showed a similar release profile of TH (f2 was 71) in in vitro release studies. The in vivo study was a two-treatment, two-period, two-sequence, single-oral dose 100 mg, crossover design using rabbit model with the phases separated by a washout period of 14 days. It was shown that the amount of TH absorbed into the systemic circulation is similar for TP and TR (the 90% confidence intervals for the AUC(0-1), AUC(0-infinity) and ratios were 85-122 and 92-107%, respectively). However, after administration of slow release tablets obtained by hot tableting of coated pellets, a prolonged absorption and elimination processes and a smoother and more extended plasma profile of TH were observed. It can be assumed that the use of a new oral dosage form of TH in patients affects the extension of analgesia after single administration of the drug, with its gradual absorption into the systemic circulation. PMID:25362810

Szkutnik-Fiedler, Danuta; Sawicki, Wies?aw; Balcerkiewicz, Monika; Mazgalski, Jaros?aw; Grabowski, Tomasz; Grze?kowiak, Edmund

2014-01-01

158

Valproate attenuates the development of morphine antinociceptive tolerance.  

PubMed

Morphine is a potent opioid analgesic. Repeated administration of morphine induces tolerance, thus reducing the effectiveness of analgesic treatment. Although some adjuvant analgesics can increase morphine analgesia, the precise molecular mechanism behind their effects remains unclear. Opioids bind to the mu opioid receptor (MOR). Morphine tolerance may be derived from alterations in the intracellular signal transduction after MOR activation. Chronic morphine treatment activates glycogen synthase kinase 3? (GSK3?), whose inhibition diminishes morphine tolerance. Valproate is widely prescribed as an anticonvulsant and a mood stabilizer for bipolar disorders because it increases the amount of ?-aminobutyric acid (GABA) in the central nervous system. Although the activation of GABAergic neurons may be responsible for the chief pharmacologic effect of valproate, recent studies have shown that valproate also suppresses GSK3? activity. We examined the effect of valproate on the development of morphine antinociceptive tolerance in a mouse model of thermal injury. Mice were treated with morphine alone or with morphine and valproate twice daily for 5 days. The resulting antinociceptive effects were assessed using a hot plate test. While mice treated with morphine developed tolerance, co-administration of valproate attenuated the development of tolerance and impaired the activation of GSK3? in mice brains. Valproate alone did not show analgesic effects; nevertheless, it functioned as an adjuvant analgesic to prevent the development of morphine tolerance. These results suggest that the modulation of GSK3? activity by valproate may be useful and may play a role in the prevention of morphine tolerance. PMID:20816918

Dobashi, Tamae; Tanabe, Serabi; Jin, Hisayo; Nishino, Takashi; Aoe, Tomohiko

2010-11-19

159

The bioavailability of morphine applied topically to cutaneous ulcers  

Microsoft Academic Search

A number of studies have reported the analgesic effect of morphine when applied topically to painful skin ulcers. It has been suggested that morphine may exert a local action, as opioid receptors have been demonstrated on peripheral nerve terminals. In this study, we investigated the bioavailability of topically applied morphine to cutaneous ulcers. Six hospice inpatients with skin ulcers were

Maria D. C. Ribeiro; Simon P. Joel; Giovambattista Zeppetella

2004-01-01

160

Changes in morphine-induced activation of cerebral Na(+),K(+)-ATPase during morphine tolerance: biochemical and behavioral consequences.  

PubMed

There is ample evidence of the biological changes produced by the sustained activation of opioid receptors. We evaluated the adaptive changes of cerebral Na(+),K(+)-ATPase in response to the sustained administration of morphine (minipumps, 45mg/kg/day, 6 days) in CD-1 mice and the functional role of these changes in opioid antinociception. The antinociceptive effect of morphine as determined with tail-flick tests was reduced in morphine-tolerant mice. There were no significant changes in the density of high-affinity Na(+),K(+)-ATPase ? subunits labeled with [(3)H]ouabain in forebrain membranes from morphine-tolerant compared to those of morphine-naive animals. Western blot analysis showed that there were no significant differences between groups in the changes in relative abundance of ?(1) and ?(3) subunits of Na(+),K(+)-ATPase in the spinal cord or forebrain. However, the morphine-induced stimulation of Na(+),K(+)-ATPase activity was significantly lower in brain synaptosomes from morphine-tolerant mice (EC(50)=1.79±0.10?M) than in synaptosomes from morphine-naive mice (EC(50)=0.69±0.12?M). Furthermore, adaptive alterations in the time-course of basal Na(+),K(+)-ATPase activity were observed after sustained morphine treatment, with a change from a bi-exponential decay model (morphine-naive mice) to a mono-exponential model (morphine-tolerant mice). In behavioral studies the antinociceptive effects of morphine (s.c.) in the tail-flick test were dose-dependently antagonized by ouabain (1 and 10ng/mouse, i.c.v.) in morphine-naive mice, but not in morphine-tolerant mice. These findings suggest that during morphine tolerance, adaptive cellular changes take place in cerebral Na(+),K(+)-ATPase activity which are of functional relevance for morphine-induced antinociception. PMID:22410004

Gonzalez, Luis G; Masocha, Willias; Sánchez-Fernández, Cristina; Agil, Ahmad; Ocaña, Maria; Del Pozo, Esperanza; Baeyens, José M

2012-06-01

161

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2010 CFR

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs. (2) Administered orally to small breeds of dogs, 1/2 to 1 tablet twice daily for several...

2010-04-01

162

21 CFR 520.2150a - Stanozolol tablets.  

Code of Federal Regulations, 2010 CFR

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice...

2010-04-01

163

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2012 CFR

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs. (2) Administered orally to small breeds of dogs, 1/2 to 1 tablet twice daily for several...

2012-04-01

164

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2013 CFR

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs. (2) Administered orally to small breeds of dogs, 1/2 to 1 tablet twice daily for several...

2013-04-01

165

21 CFR 520.2150a - Stanozolol tablets.  

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice...

2014-04-01

166

21 CFR 520.2150b - Stanozolol chewable tablets.  

Code of Federal Regulations, 2011 CFR

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs. (2) Administered orally to small breeds of dogs, 1/2 to 1 tablet twice daily for several...

2011-04-01

167

21 CFR 520.2150b - Stanozolol chewable tablets.  

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs. (2) Administered orally to small breeds of dogs, 1/2 to 1 tablet twice daily for several...

2014-04-01

168

21 CFR 520.2150a - Stanozolol tablets.  

Code of Federal Regulations, 2013 CFR

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice...

2013-04-01

169

21 CFR 520.2150a - Stanozolol tablets.  

Code of Federal Regulations, 2012 CFR

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice...

2012-04-01

170

21 CFR 520.2150a - Stanozolol tablets.  

Code of Federal Regulations, 2011 CFR

...b) Sponsor. No. 000009 in § 510.600(c) of this chapter. (c) Conditions of use. (1) Used as an anabolic steroid treatment in dogs and cats. (2) Administered orally to cats and small breeds of dogs, 1/2 to 1 tablet twice...

2011-04-01

171

Morphine hydro­chloride anhydrate1  

PubMed Central

In the title mol­ecular salt [systematic name: (5?,6?)-7,8-didehydro-4,5-ep­oxy-17-methyl­morphinan-3,6-diol hydro­chloride], C17H20NO3 +·Cl?, the conformation of the morphinium ion is in agreement with the characteristics of the previously reported morphine forms [for example, Gylbert (1973 ?). Acta Cryst. B29, 1630–1635]. In the crystal, the cations and chloride anions are linked into a helical chain propagating parallel to the b-axis direction by N—H?Cl and O—H?Cl hydrogen bonds. The title salt and the morphine monohydrate [Bye (1976 ?) Acta Chem. Scand. 30, 549–554] display very similar one-dimensional packing modes of their morphine components. PMID:23476193

Gelbrich, Thomas; Braun, Doris E.; Griesser, Ulrich J.

2012-01-01

172

Calcium depletion of synaptosomes after morphine treatment.  

PubMed Central

It was confirmed that morphine administration in vivo produced a selective decrease in the calcium content of synaptosomal fractions prepared from rat cerebral cortices. This effect was prevented by naloxone. 2 After morphine or naloxone, there were no changes in the sodium, potassium and magnesium contents of any of the seven subcellular fractions tested. 3 Since the selective calcium loss was found to occur from fractions similar to those reported to exhibit opiate receptor binding, it is concluded that calcium may play a role in the action of narcotic agonist drugs. PMID:963340

Cardenas, H L; Ross, D H

1976-01-01

173

Synthetic substances with morphine-like effect  

PubMed Central

A review of effects in man of morphine-like drugs which have been brought under international narcotics control is presented in the form of individual monographs. These are based on controlled observations with quantitative data and significant reports of results obtained in medical practice. In a summarizing section, the drugs are compared with respect to effectiveness, side-effects and addiction liability. Morphine-like drugs of natural and synthetic origin now cover a wide range of potency (analgesic, antitussive), not necessarily paralleled by incidence of side-effects or addiction liability. PMID:13511135

Eddy, Nathan B.; Halbach, H.; Braenden, Olav J.

1957-01-01

174

Microstructural investigation of tablet compaction and tablet pharmacological properties  

E-print Network

In current tablet manufacturing processes, there is a knowledge gap concerning material transformation and the subsequent impact on tablet properties; this gap presents a barrier to rational formulation / process design. ...

Mao, Kangyi

2010-01-01

175

In vivo bioavailability studies of sumatriptan succinate buccal tablets  

PubMed Central

Back ground and the purpose of study Sumatriptan succinate is a Serotonin 5- HT1 receptor agonist, used in treatment of migraine. It is absorbed rapidly but incompletely when given orally and undergoes first-pass metabolism, resulting in a low absolute bioavailability of about 15%. The aim of this work was to design mucoadhesive bilayered buccal tablets of sumatriptan succinate to improve its bioavailability. Methods Mucoadhesive polymers carbopol 934 (Carbopol), HPMC K4M, HPMC K15M along with ethyl cellulose as an impermeable backing layer were used for the preparation of mucoadhesive bilayered tablets. In vivo bioavailability studies was also conducted in rabbits for optimized formulation using oral solution of sumatriptan succinate as standard. Results Bilayered buccal tablets (BBT) containing the mixture of Carbopol and HPMC K4M in the ratio 1:1 (T1) had the maximum percentage of in vitro drug release within 6 hrs. The optimized formulation (T1) followed non-Fickian release mechanism. The percentage relative bioavailability of sumatriptan succinate from selected bilayered buccal tablets (T1) was found to be 140.78%. Conclusions Bilayered buccal tablets of sumatriptan succinate was successfully prepared with improved bioavailability. PMID:22615661

Shivanand, K; Raju, SA; Nizamuddin, S; Jayakar, B

2011-01-01

176

Effects of morphine and morphine withdrawal on adrenergic neurons of the rat rostral ventrolateral medulla  

Microsoft Academic Search

In urethane anesthetized rats, iontophoretic application of morphine or ?-methylnoradrenaline (?-MNE) inhibited (80–100%) the discharges of all putative adrenergic (C1) cells of the rostral ventrolateral medulla (RVLM). The effect of morphine was blocked selectively by naloxone while that of ?-MNE was blocked selectively by the?2-adrenergic antagonist idazoxan. Putative C1 cells were inhibited (75–100%) by low i.v. doses of clonidine (10–15

Scott C. Baraban; Ruth L. Stornetta; Patrice G. Guyenet

1995-01-01

177

Time dependent antinociceptive effects of morphine and tramadol in the hot plate test: using different methods of drug administration in female rats.  

PubMed

Morphine and tramadol which have analgesic effects can be administered acutely or chronically. This study tried to investigate the effect of these drugs at various times by using different methods of administration (intraperitoneal, oral, acute and chronic). Sixty adult female rats were divided into six groups. They received saline, morphine or tramadol (20 to 125 mg/Kg) daily for 15 days. A hot plate test was performed for the rats at the 1(st), 8(th) and 15(th) days. After drug withdrawal, the hot plate test was repeated at the 17(th), 19(th), and 22(nd) days. There was a significant correlation between the day, drug, group, and their interaction (P<0.001). At 1(st) day (d1), both morphine, and tramadol caused an increase in the hot plate time comparing to the saline groups (P<0.001), while there was no correlation between drug administration methods of morphine and/or tramadol. At the 8(th) day (d8), morphine and tramadol led to the most powerful analgesic effect comparing to the other experimental days (P<0.001). At the 15(th) day (d15), their effects diminished comparing to the d8. After drug withdrawal, analgesic effect of morphine, and tramadol disappeared. It can be concluded that the analgesic effect of morphine and tramadol increases with the repeated use of them. Thereafter, it may gradually decrease and reach to a level compatible to d1. The present data also indicated that although the analgesic effect of morphine and tramadol is dose-and-time dependent, but chronic exposure to them may not lead to altered nociceptive responses later in life. PMID:25561936

Gholami, Morteza; Saboory, Ehsan; Mehraban, Sogol; Niakani, Afsaneh; Banihabib, Nafiseh; Azad, Mohamad-Reza; Fereidoni, Javid

2015-01-01

178

Time Dependent Antinociceptive Effects of Morphine and Tramadol in the Hot Plate Test: Using Different Methods of Drug Administration in Female Rats  

PubMed Central

Morphine and tramadol which have analgesic effects can be administered acutely or chronically. This study tried to investigate the effect of these drugs at various times by using different methods of administration (intraperitoneal, oral, acute and chronic). Sixty adult female rats were divided into six groups. They received saline, morphine or tramadol (20 to 125 mg/Kg) daily for 15 days. A hot plate test was performed for the rats at the 1st, 8th and 15th days. After drug withdrawal, the hot plate test was repeated at the 17th, 19th, and 22nd days. There was a significant correlation between the day, drug, group, and their interaction (P<0.001). At 1st day (d1), both morphine, and tramadol caused an increase in the hot plate time comparing to the saline groups (P<0.001), while there was no correlation between drug administration methods of morphine and/or tramadol. At the 8th day (d8), morphine and tramadol led to the most powerful analgesic effect comparing to the other experimental days (P<0.001). At the 15th day (d15), their effects diminished comparing to the d8. After drug withdrawal, analgesic effect of morphine, and tramadol disappeared. It can be concluded that the analgesic effect of morphine and tramadol increases with the repeated use of them. Thereafter, it may gradually decrease and reach to a level compatible to d1. The present data also indicated that although the analgesic effect of morphine and tramadol is dose-and-time dependent, but chronic exposure to them may not lead to altered nociceptive responses later in life. PMID:25561936

Gholami, Morteza; Saboory, Ehsan; Mehraban, Sogol; Niakani, Afsaneh; Banihabib, Nafiseh; Azad, Mohamad-Reza; Fereidoni, Javid

2015-01-01

179

Study of the clomipramine-morphine interaction in the forced swimming test in mice  

Microsoft Academic Search

Tricyclic antidepressant-morphine interactions have been extensively studied on pain tests but less often on tests predictive of antidepressant activity. The effects of clomipramine (CMI) and morphine were tested on the forced swimming test in mice after pretreatment with CMI, morphine or saline. Like CMI, though less so, morphine was significantly active. Morphine pretreatment partially inhibited the effect of CMI irrespective

A. Eschalier; J. Fialip; O. Varoquaux; M.-C. Makambila

1987-01-01

180

Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts  

PubMed Central

This double-blind, placebo-controlled study investigated effects of oral morphine (0, 45, 135 mg/70kg) and oral oxycodone (0, 15, 45 mg/70kg) in buprenorphine-maintained opioid addicts. Since a 3:1 morphine:oxycodone dose ratio had yielded equivalent subjective and physiological effects in non-dependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures, i.e. a drug vs. money and a drug vs. drug procedure, were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater compared to high-dose morphine. The study demonstrated that a 3:1 dose ratio of morphine:oxycodone was not equipotent in buprenorphine-dependent subjects. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

2014-01-01

181

Topical cannabinoid enhances topical morphine antinociception  

Microsoft Academic Search

Opioids and cannabinoids produce antinociception through both spinal and supraspinal action. Both opioids and cannabinoids also have important peripheral action. Many previous studies indicate that systemically administered cannabinoids enhance antinociceptive properties of opioids. Experiments were conducted to test the hypothesis that topical cannabinoids would enhance the topical antinociceptive effects of morphine. Antinociception was measured in the radiant tail-flick test after

Ozgur Yesilyurt; Ahmet Dogrul; Husamettin Gul; Melik Seyrek; Ozkan Kusmez; Yalcin Ozkan; Oguzhan Yildiz

2003-01-01

182

Influences of Gender on Postoperative Morphine Consumption  

PubMed Central

Background: Gender related differences on morphine consumption during postoperative period following abdominal surgeries. Materials and Methods: Four hundred and fifty ASA I & II patients of either sex (male =231, female = 219), between the age group of 18-65 y undergoing elective intra abdominal surgeries under general anaesthesia were included for the study. Patients with preexisting pain either acute or chronic preoperatively were excluded from the study. Anaesthesia and analgesia protocol during surgery was standardized. Postoperatively, a loading dose was given to achieve the visual analogue scale (VAS) of ?30 and subjects were connected to patient control analgesia (PCA) pump containing 0.4 mg/ml of morphine configured to deliver a bolus dose (1 mg) with a 5 min lock-out period. The total analgesic requirements along with VAS (visual analog scale) score were analysed between males and females in the first 24 h postoperatively. All demographic data and between group comparisons were analysed with student t-test. Within group comparisons were done by using one-way-ANOVA test and Tukey’s Honestly significant Difference test. Results: During the first 24 h, males consumed significantly higher amount of morphine (34.35 ± 6.68 mg) when compared to females (26.78 ± 7.14 mg), p < 0.001. Conclusion: We conclude that men require more morphine in the postoperative period than women.

Poovathai, Raja; Pondiyadanar, Srinivasan

2014-01-01

183

Impact of cefpodoxime proxetil and amoxicillin on the normal oral and intestinal microflora  

Microsoft Academic Search

Ten healthy volunteers were given 200 mg cefpodoxime proxetil tablets every 12 h and ten volunteers received 500 mg amoxicillin tablets every 8 h for seven days and the impact of the agents on the oral and intestinal microflora was studied. In the oral microflora, only minor alterations were observed in both groups. In subjects receiving cefpodoxime proxetil, the numbers

B. Brismar; C. Edlund; C. E. Nord

1993-01-01

184

Obtaining fast dissolving disintegrating tablets with different doses of melatonin.  

PubMed

Fast dissolving disintegrating tablets (FDDTs) containing different dosages of melatonin have been manufactured for administration to a specific target population: pediatric patients, having potential difficulties taking other oral forms. The lower dosages (3 and 5mg) are intended for epileptic children, migraine prevention, neurodevelopmental disability, sleep disorders and blindness. Dosages of 10 and 60 mg are intended for Duchenne muscular dystrophy. Two FDDT groups have been designed, one which has excipients for direct compression and others having direct compression and effervescent excipients. Tablets have been produced having disintegration times of less than 25s and with friability and hardness values that require no special storage or packaging conditions. PMID:24699354

Muñoz, H; Castan, H; Clares, B; Ruiz, M A

2014-06-01

185

Effects of morphine and morphine withdrawal on adrenergic neurons of the rat rostral ventrolateral medulla.  

PubMed

In urethane anesthetized rats, iontophoretic application of morphine or alpha-methylnoradrenaline (alpha-MNE) inhibited (80-100%) the discharges of all putative adrenergic (C1) cells of the rostral ventrolateral medulla (RVLM). The effect of morphine was blocked selectively by naloxone while that of alpha-MNE was blocked selectively by the alpha 2-adrenergic antagonist idazoxan. Putative C1 cells were inhibited (75-100%) by low i.v. doses of clonidine (10-15 micrograms/kg). Most cells (7/10) were also inhibited by morphine i.v. (81% at 7 mg/kg). Two cells were slightly excited at doses below 2 mg/kg and inhibited at higher doses. Three cells were excited only. All effects of morphine i.v. were reversed by naloxone (1 mg/kg, i.v.). Intravenous administration of naloxone to morphine-dependent rats increased significantly the firing rate of all putative C1 adrenergic cells (from 5.8 +/- 0.9 spikes/s to 12.3 +/- 1.5 spikes/s; n = 8). During withdrawal these cells could still be inhibited (80-100%) by i.v. injection of clonidine (15 micrograms/kg). C-Fos expression induced by naltrexone-precipitated withdrawal was examined in the brainstem of freely moving morphine-dependent rats pretreated with clonidine or saline before injection of the opioid antagonist. The locus coeruleus (LC) of the same rats was examined for comparison. Morphine withdrawal without clonidine treatment significantly increased the number of Fos-like-immunoreactive (Fos-LIR) cells in the RVLM and LC. Clonidine pretreatment (1 mg/kg, i.p.) reduced the number of withdrawal-activated Fos-LIR cells in LC by 81%. In the RVLM this reduction averaged 37% for all cell types and 48% for C1 adrenergic cells. Further, a very large proportion of RVLM neurons that expressed c-Fos during morphine withdrawal (83%) were immunoreactive for alpha 2A-adrenergic receptors. This study suggests that, like noradrenergic cells of the LC, C1 adrenergic neurons of the RVLM are: (i) inhibited by both opiate and alpha 2-adrenergic receptor agonists; and (ii) activated during naloxone-precipitated morphine withdrawal. Since C1 cells are considered essential to sympathetic tone generation, their inhibition by morphine may contribute to the hypotensive effects of this opioid agonist in non-dependent individuals. Their excitation during opiate withdrawal may also contribute to the autonomic activation that characterizes this syndrome. Finally, inhibition of C1 cells by clonidine may contribute to the clinically recognized efficacy of this drug to attenuate autonomic signs of opiate withdrawal. PMID:7542145

Baraban, S C; Stornetta, R L; Guyenet, P G

1995-04-10

186

Randomized controlled study transitioning opioid-dependent pregnant women from short-acting morphine to buprenorphine or methadone  

Microsoft Academic Search

This study compared the safety and withdrawal discomfort associated with transitioning pregnant opioid-dependent women from short-acting morphine onto buprenorphine or methadone under well-controlled double-blind conditions. Participants (n=18) were patients in a comprehensive treatment setting and were part of a larger randomized controlled trial comparing the neonatal abstinence syndrome in mothers treated with individualized doses of sublingual buprenorphine or oral methadone.

Hendree E. Jones; Rolley E. Johnson; Donald R. Jasinski; Lorraine Milio

2005-01-01

187

The analgesic action of morphine-N-oxide  

PubMed Central

1. The analgesic activity of morphine-N-oxide in mice and rats has been investigated and compared with that of morphine. 2. Both morphine and morphine-N-oxide were more active when given subcutaneously than when given intraperitoneally. 3. Given subcutaneously, morphine was 11-22 times more potent than morphine-N-oxide and when given intraperitoneally it was 39-89 times more potent. The potencies depended on the test situation and the species of animal used. 4. In animals pretreated with amiphenazole or tacrine, the analgesic activities of morphine and morphine-N-oxide were increased. The potencies of these analgesic drugs given intraperitoneally were increased to a greater extent than were the potencies obtained by subcutaneous administration. 5. A possible explanation for the increase in analgesic potency of morphine-N-oxide produced by pretreatment with amiphenazole or tacrine may be that morphine-N-oxide is rapidly inactivated in the liver and this inactivation is impaired by amiphenazole and tacrine. PMID:5687589

Fennessy, M. R.

1968-01-01

188

An open-label, randomized bioavailability study with alternative methods of administration of crushed ticagrelor tablets in healthy volunteers  

PubMed Central

Objective: To compare the bioavailability and safety profile of crushed ticagrelor tablets suspended in water and administered orally or via nasogastric tube, with that of whole tablets administered orally. Methods: In this single-center, open-label, randomized, three-treatment crossover study, 36 healthy volunteers were randomized to receive a single 90-mg dose of ticagrelor administered orally as a whole tablet or as crushed tablets suspended in water and given orally or via a nasogastric tube into the stomach, with a minimum 7-day wash-out between treatments. Plasma concentrations of ticagrelor and AR-C124910XX were assessed at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours post-ticagrelor dose for pharmacokinetic analyses. Safety and tolerability was assessed throughout the study. Results: At 0.5 hours postdose, plasma concentrations of ticagrelor and AR-C124910XX were higher with crushed tablets administered orally (148.6 ng/mL and 13.0 ng/mL, respectively) or via nasogastric tube (264.6 ng/mL and 28.6 ng/mL, respectively) compared with whole-tablet administration (33.3 ng/mL and 5.2 ng/mL, respectively). A similar trend was observed at 1 hour postdose. Ticagrelor tmax was shorter following crushed vs. whole-tablet administration (1 vs. 2 hours, respectively). Geometric mean ratios between treatments for AUC and Cmax were contained within the bioequivalence limits of 80 – 125% for ticagrelor and AR-C124910XX. All treatments were generally well tolerated. Conclusions: Ticagrelor administered as a crushed tablet is bioequivalent to whole-tablet administration, independent of mode of administration (oral or via nasogastric tube), and resulted in increased plasma concentrations of ticagrelor and AR-C124910XX at early timepoints. PMID:25500486

Teng, Renli; Carlson, Glenn; Hsia, Judith

2015-01-01

189

Chronic morphine treatment inhibits oxytocin synthesis in rats.  

PubMed

The changes of oxytocin content and mRNA expression in some nuclei were investigated in morphine-dependent rats using radioimmunoassay (RIA) and in situ hybridization (ISH). After chronic administration of morphine, the oxytocin content in supraoptic nucleus (SON) and nucleus accumbens (NAc) decreased, and increased in the ventral tegment area (VTA) and locus coeruleus (LC), but did not change in other nuclei including the paraventricular nucleus (PVN), lateral septum (SEPTUM), raphe magnus nucleus (NRM) and periaquaductal gray (PAG). In morphine-L dependent rats, naloxone increased the levels of oxytocin in SON and PVN, but decreased that in LC. ISH first showed that chronic morphine treatment inhibited the oxytocin synthesis in SON but not in PVN. The present study demonstrates that chronic morphine treatment alters the brain oxytocin system, suggesting that oxytocin might contribute to the behavioral and neuroendocrine responses to morphine. PMID:11043533

You, Z D; Li, J H; Song, C Y; Wang, C H; Lu, C L

2000-09-28

190

CES 2011: Tablet Crazy  

ERIC Educational Resources Information Center

Ereaders are so last year. Tablets were the watchword at this year's annual Consumer Electronics Show (CES) in Las Vegas, January 6-9. This year, the show set new records, with some 2700 companies from around the world exhibiting at the multiple exhibition halls and 30,000 attendees gawking at the products. What did they see? There were still some…

Rapp, David

2011-01-01

191

Aloe vera Aqueous Extract Effect on Morphine Withdrawal Syndrome in Morphine-Dependent Female Rats  

PubMed Central

Background: Aloe vera is a medicinal herb used as an anti-inflammatory and sedative agent. Objectives: The current study aimed to evaluate the effect of Aloe vera aqueous extract on morphine withdrawal symptoms in morphine-dependent female rats. Patients and Methods: The current research was performed on 40 female Wista-Albino rats which were made dependent on morphine using Houshyar protocol and were randomly divided into five groups (A, B, C, D, and E). Group A did not receive any agent in the period of handling but other groups (B, C, D and E) received 5, 10, 20 and 40 mg/kg of Aloe vera aqueous extract by gavage, three times daily for a week, respectively. Withdrawal symptoms, stool form, agitation, disparity, floppy eyelids, and body mass variations were checked for 10 days. The obtained data were analyzed using SPSS v.11 software, and Friedman, Kruskal-Wallis, and Mann-Whitney statistical tests. Statistical difference was considered significant (P < 0.05). Results: The results of the present study showed that agitation, disparity, and floppy eyelids in group E were significantly higher than those of others groups; however, these symptoms in group C were significantly lower than those of the other groups. Conclusions: The results of the present study revealed that the Aloe vera aqueous extract had various effects on morphine withdrawal syndrome in morphine-dependent female rats . PMID:25593890

Shahraki, Mohammad Reza; Mirshekari, Hamideh; Sabri, Azame

2014-01-01

192

Morphine-Induced Degradation of the Host Defense Barrier  

Microsoft Academic Search

The effect of morphine on intestinal ulcer formation and on the degradation of the host defense barrier was studied. Mice\\u000a receiving morphine (MRM) showed mucosal ulcer formation in the ileum and in the upper third of the colon. In in vitro studies, morphine enhanced apoptosis of cultured human colonic cells (HCC). Nitric oxide synthase (NOS) inhibitors attenuated\\u000a the proapoptotic effect

Lia Frenklakh; Rajani S. Bhat; Madhu Bhaskaran; Shilpa Sharma; Meera Sharma; Amit Dinda; Pravin C. Singhal

2006-01-01

193

The effect of morphine consumption on plasma corticosteron concentration and placenta development in pregnant rats  

PubMed Central

Background: Previous studies have shown that morphine consumption during pregnancy may delay embryo development or cause abnormal nervous system function. Objective: The present study focused on the effect of maternal morphine consumption on development of placenta and blood corticosteron concentration in addictive pregnant mothers. Materials and Methods: 24 female rats, 170-200g weight, were used. The experimental groups after pregnancy received an oral dose of 0.05 mg/ml of morphine by tap water while the control group received only tap water. On 10th and 14th day of pregnancy, rats were anesthetized and placenta removed surgically, 1ml blood was collected from each pregnant mother from retro-orbital sinus, the concentration of blood corticosteron was determined by corticosteron Elisa kit after centrifugation. The fixed tissue was processed, sectioned and stained with hematoxylin and eosin. Placenta was studied microscopically according to the thickness of layers, area of blood cisterns, and the number of cells. Results: Comparing the plasma corticosteron concentration of the treatment and the control groups, not only a severe increase in the treatment group was detected, but also the thickness of maternal and embryonic portions of the placenta at day 10th and 14th of gestation was different significantly (p?0.05). Furthermore, an increase in number of cells in maternal and embryonic portion of placenta and a decrease in blood cistern area were demonstrated in both the experimental and the control groups. Conclusion: The effects of morphine, including an increase in blood concentration of corticosteron, in dependent pregnant mothers were seen. Development of placenta in the experimental group was delayed.

Kazemi, Masoomeh; Sahraei, Hedayat; Azarnia, Mahnaz; Dehghani, Leila; Bahadoran, Hossein; Tekieh, Elaheh

2011-01-01

194

Cingulate metabolites during pain and morphine treatment as assessed by magnetic resonance spectroscopy  

PubMed Central

Background Experimental investigation of cerebral mechanisms underlying pain and analgesia are important in the development of methods for diagnosis and treatment of pain. The aim of the current study was to explore brain metabolites in response to pain and treatment with morphine. Methods Proton magnetic resonance spectroscopy of the anterior cingulate cortex was performed in 20 healthy volunteers (13 males and seven females, aged 24.9±2.6 years) during rest and acute pain before and during treatment with 30 mg of oral morphine or placebo in a randomized, double-blinded, cross-over study design. Pain was evoked by skin stimulation applied to the right upper leg using a contact heat-evoked potential stimulator. Results Data from 12 subjects were valid for analysis. Painful stimulation induced an increase in N-acetylaspartate/creatine compared with rest (F=5.5, P=0.04). During treatment with morphine, painful stimulation induced decreased glutamate/creatine (F=7.3, P=0.02), myo-inositol/creatine (F=8.38, P=0.02), and N-acetylaspartate/creatine (F=13.8, P=0.004) concentrations, whereas an increase in the pain-evoked N-acetylaspartate/creatine concentration (F=6.1, P=0.04) was seen during treatment with placebo. Conclusion This explorative study indicates that neuronal metabolites in the anterior cingulate cortex, such as N-acetylaspartate, glutamate, and myo-inositol, could be related to the physiology of pain and treatment with morphine. This experimental method has the potential to enable the study of brain metabolites involved in pain and its treatment, and may in the future be used to provide further insight into these mechanisms. PMID:24899823

Hansen, Tine Maria; Olesen, Anne Estrup; Simonsen, Carsten Wiberg; Drewes, Asbjørn Mohr; Frøkjær, Jens Brøndum

2014-01-01

195

Epidural and intravenous bolus morphine for postoperative analgesia in infants  

Microsoft Academic Search

Purpose  To compare two doses of bolus epidural morphine with bolus iv morphine for postoperative pain after abdominal or genitourinary\\u000a surgery in infants.\\u000a \\u000a \\u000a \\u000a Methods  Eighteen infants were randomly assigned to bolus epidural morphine (0.025 mg · kg?1 or 0.050 mg · kg?1) or bolus iv morphine (0.050–0.150 mg · kg?1). Postoperative pain was assessed and analgesia provided, using a modified infant pain

Charles M. Haberkern; Anne M. Lynn; Jeremy M. Geiduschek; Mary Kay Nespeca; Lawrence E. Jacobson; Susan L. Bratton; Maureen Pomietto

1996-01-01

196

The Neurodevelopmental Impact of Neonatal Morphine Administration  

PubMed Central

Medical management of newborn infants often necessitates recurrent painful procedures, which may alter nociceptive pathways during a critical developmental period and adversely effect neuropsychological outcomes. To mitigate the effects of repeated painful stimuli, opioid administration for peri-procedural analgesia and ICU (intensive care unit) sedation is common in the NICU (neonatal intensive care unit). A growing body of basic and animal evidence suggests potential long-term harm associated with neonatal opioid therapy. Morphine increases apoptosis in human microglial cells, and animal studies demonstrate long-term changes in behavior, brain function, and spatial recognition memory following morphine exposure. This comprehensive review examines existing preclinical and clinical evidence on the long-term impacts of neonatal pain and opioid therapy. PMID:24961764

Attarian, Stephanie; Tran, Lan Chi; Moore, Aimee; Stanton, George; Meyer, Eric; Moore, Robert P.

2014-01-01

197

The interaction between IL1? and morphine: possible mechanism of the deficiency of morphine-induced analgesia in diabetic mice  

Microsoft Academic Search

It is known that diabetic mice are less sensitive to the analgesic effect of morphine. Some factor(s) derived from mononuclear cells, e.g. interleukin-1? (IL-1?), may be responsible for the diminished analgesic effect of morphine in diabetic mice. Therefore, we examined direct effects of IL-1?, intracerebroventricularly (i.c.v.), on morphine-induced analgesia, subcutaneously (s.c.), in diabetic and control mice by using the tail-flick

Husamettin Gul; Oguzhan Yildiz; Ahmet Dogrul; Ozgur Yesilyurt; Askin Isimer

2000-01-01

198

Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.  

PubMed Central

1. The pharmacokinetics of ethylmorphine after administration of a single dose of the cough mixture Cosylan were investigated in 10 healthy subjects. 2. The median urinary recovery of ethylmorphine and measured metabolites was 77% over 48 h. The median tmax of unchanged ethylmorphine was 45 min, and the terminal elimination t1/2 was 2 h. Ethylmorphine-6-glucuronide was found to be the major metabolite. 3. Two subjects had significantly lower urinary recovery (0.48 h) of morphine and morphine-glucuronides than the remainder. Furthermore, these two had urinary metabolic ratios (MRO) and partial metabolic clearances (CLmO) for O-deethylation of ethylmorphine tentatively classifying them phenotypically as poor metabolisers of the debrisoquine/sparteine type. 4. Genotyping for cytochrome P450 (CYP) 2D6 alleles revealed five homozygote (wt/wt) and five heterozygote subjects. Two subjects phenotypically classified as poor metabolisers were genotypically CYP2D6A/wt and CYP2D6D/wt, respectively. 5. Serum and urine samples taken more than 8 and 24 h after administration of ethyl-morphine respectively, contained morphine and morphine-glucuronides, but no ethylmorphine, ethylmorphine-6-glucuronide or (serum only) norethylmorphine. Norethylmorphine could be detected after hydrolysis of urine samples in all subjects. The urinary recovery of the active metabolites morphine and morphine-6-glucuronide after administration of ethylmorphine varied by a factor of 9 between individuals. 6. The wide variation in recovery of morphine and morphine-glucuronides after oral administration of ethylmorphine could not be explained simply by a difference in CYP2D6 genotype. Constitutional variation in other enzymatic pathways involved in ethylmorphine metabolism is probably crucial. Ratios of morphine to parent drug cannot be used to distinguish the source of morphine after administration of ethylmorphine. Norethylmorphine should be included in urine assays for opiates in forensic toxicology, and no firm conclusions about the source of morphine are possible based on serum samples obtained more than 24 h after drug administration. PMID:7654478

Aasmundstad, T A; Xu, B Q; Johansson, I; Ripel, A; Bjørneboe, A; Christophersen, A S; Bodd, E; Mørland, J

1995-01-01

199

In vitro--in vivo evaluation of tableted caseinchitosan microspheres containing diltiazem hydrochloride.  

PubMed

Casein-chitosan microspheres containing diltiazem hydrochloride (DTZ.HCL) were prepared using aqueous coacervation technique. The formed microspheres were not suitable for tableting by direct compression due to their poor binding properties. The effect of hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), carbopol 940 and egg albumin as dry binders at different concentrations on the properties of the tablets was studied. Each blend of microspheres with dry binder and 2% w/w magnesium stearate as glidant was hand-filled into the die cavity of a single punch tablet machine to ensure constant amount of drug (90 mg) in each tablet. The compression force was adjusted to produce tablets with hardness value about 7.73 +/- 0.79 Kp. The prepared tablets showed good appearance and low friability. The tested binders HPMC (10 and 30% w/w) and EC (20 and 30% w/w) gave fast tablet disintegration with high initial drug release (burst effect) while, carbopol 940 (5 and 10% w/w) and egg albumin (30% w/w) gave non-disintegrating tablets with low initial drug release. Tableted microspheres prepared with 30% egg albumin showed drug release profile similar to one of the commercial tablets (Dilzem retard, 90 mg) and was chosen for in-vivo study. Tableted microspheres and commercial tablets were administered orally in different occasions to six beagle dogs and diltiazem was assayed in dog plasma. The pharmacokinetic parameters including maximum drug concentration (Cmax) and time to reach that maximum (Tmax) were 106.24 +/- 17.96 ng.ml-1 and 5.8 +/- 2.04 hours, respectively, for the commercial sustained release DTZ tablets while, those were 107.9 +/- 12.89 ng.ml-1 and 3.6 +/- 1.36 hours, respectively for tableted microspheres. The elimination half-lives were nearly the same for the commercial and the formulated tablets (8.22 +/- 4.19 and 7.95 +/- 4.28 hours, respectively). No statistical differences (P > 0.05) were found between the two treatments for area under the plasma concentration curve (AUC0 infinity), mean residence time (MRT) and rate of drug absorption (Cmax/AUC0 infinity) indicating comparable extent and rate of drug absorption for both formulations. It was concluded that the formulated tableted microspheres provide an acceptable delivery for DTZ over an extended period of time. PMID:12680034

al-Suwayeh, Saleh A; el-Helw, Abdel-Rehim M; al-Mesned, Abdullah F; Bayomi, Mohsen A; el-Gorashi, Abobakr S

2003-01-01

200

Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride.  

PubMed

Tizanidine hydrochloride is an orally administered prokinetic agent that facilitates or restores motility through-out the length of the gastrointestinal tract. The objective of the present investigation was to develop effervescent floating matrix tablets of tizanidine hydrochloride for prolongation of gastric residence time in order to overcome its low bioavailability (34-40 %) and short biological half life (4.2 h). Tablets were prepared by the direct compression method, using different viscosity grades of hydroxypropyl methylcellulose (HPMC K4M, K15M and K100M). Tablets were evaluated for various physical parameters and floating properties. Further, tablets were studied for in vitro drug release characteristics in 12 hours. Drug release from effervescent floating matrix tablets was sustained over 12 h with buoyant properties. DSC study revealed that there is no drug excipient interaction. Based on the release kinetics, all formulations best fitted the Higuchi, first-order model and non-Fickian as the mechanism of drug release. Optimized formulation (F9) was selected based on the similarity factor (f2) (74.2), dissolution efficiency at 2, 6 and 8 h, and t50 (5.4 h) and was used in radiographic studies by incorporating BaSO4. In vivo X-ray studies in human volunteers showed that the mean gastric residence time was 6.2 ± 0.2 h. PMID:21684848

Someshwar, Komuravelly; Chithaluru, Kalyani; Ramarao, Tadikonda; Kumar, K K Kalyan

2011-06-01

201

Mucoadhesive bilayered tablets for buccal sustained release of flurbiprofen.  

PubMed

The aim of this work was the design of sustained-release mucoadhesive bilayered tablets, using mixtures of mucoadhesive polymers and an inorganic matrix (hydrotalcite), for the topical administration of flurbiprofen in the oral cavity. The first layer, responsible for the tablet retention on the mucosa, was prepared by compression of a cellulose derivative and polyacrylic derivative blend. The second layer, responsible for buccal drug delivery, was obtained by compression of a mixture of the same (first layer) mucoadhesive polymers and hydrotalcite containing flurbiprofen. Nonmedicated tablets were evaluated in terms of swelling, mucosal adhesion, and organoleptic characteristics; in vitro and in vivo release studies of flurbiprofen-loaded tablets were performed as well. The best results were obtained from the tablets containing 20 mg of flurbiprofen, which allowed a good anti-inflammatory sustained release in the buccal cavity for 12 hours, ensuring efficacious salivary concentrations, and led to no irritation. This mucoadhesive formulation offers many advantages over buccal lozenges because it allows for reduction in daily administrations and daily drug dosage and is suitable for the treatment of irritation, pain, and discomfort associated with gingivitis, sore throats, laryngopharyngitis, cold, and periodontal surgery. Moreover, it adheres well to the gum and is simple to apply, which means that patient compliance is improved. PMID:17915804

Perioli, Luana; Ambrogi, Valeria; Giovagnoli, Stefano; Ricci, Maurizio; Blasi, Paolo; Rossi, Carlo

2007-01-01

202

21 CFR 520.581 - Dichlorophene tablets.  

Code of Federal Regulations, 2010 CFR

... § 520.581 Dichlorophene tablets. (a) Specifications. Each tablet contains 1 gram of dichlorophene...Amount. Single dose of 1 tablet (1 gram of dichlorophene...foods and milk for at least 12 hours prior to medication...

2010-04-01

203

21 CFR 520.812 - Enrofloxacin tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 false Enrofloxacin tablets. 520.812 Section 520... § 520.812 Enrofloxacin tablets. (a) Specifications. Each tablet contains either 22.7, 68...divided into 2 equal doses at 12 hour intervals,...

2010-04-01

204

21 CFR 520.455 - Clomipramine tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 false Clomipramine tablets. 520.455 Section 520... § 520.455 Clomipramine tablets. (a) Specifications. Each tablet contains 5, 20, 40, or 80...veterinarian. [64 FR 1762, Jan. 12, 1999, as amended at 72...

2010-04-01

205

Morphine, but not Trauma, Sensitizes to Systemic Acinetobacter baumannii Infection  

PubMed Central

Acinetobacter baumannii is an important nosocomial pathogen in civilian intensive care units. Recently the incidence has increased in wounded military personnel. Morphine is documented in numerous animal studies to be immunosuppressive and to sensitize to infection. The hypotheses were tested that morphine, administered for analgesia in the battlefield, predisposes to Acinetobacter infection, and that the opioid may have an additive or synergistic effect with trauma. To test these hypotheses, an intraperitoneal infection model was established in mice using several Acinetobacter strains. Morphine administered for 48 hr by implantation of a slow-release morphine pellet increased mortality compared to animals receiving a placebo pellet, an effect that was blocked by the mu-opioid receptor antagonist, naltrexone. Acinetobacter burdens in the blood, spleens, livers, and lungs of morphine-treated mice, were significantly higher than those in placebo-treated animals, confirming that mortality was due to potentiated growth of the bacteria. There were also elevated levels of pro-inflammatory cytokines in morphine-treated versus placebo-treated mice. Morphine caused a reduction in the total number of cells in the peritoneal cavity, a decrease in the percentage and total numbers of neutrophils, and a decrease in the total number of macrophages. Morphine treatment also suppressed levels of the neutrophil-inducing molecules, IL-17A and KC/CXCL1. However, IL-17A?/? mice given morphine were not sensitized to Acintobacter infection to a greater degree than similarly treated wild-type mice. Trauma alone did not sensitize to Acinetobacter infection, and there was no additive effect between morphine and trauma. These results support the hypothesis that morphine potentiates Acinetobacter infection. PMID:21826405

Breslow, Jessica M.; Monroy, M. Alexandra; Daly, John M.; Meissler, Joseph J.; Gaughan, John; Adler, Martin W.; Eisenstein, Toby K.

2014-01-01

206

Research studies on the quality of bio-mucoadhesive tablets containing miconazole nitrate.  

PubMed

Biomucoadhesive tablets are widely used to formulate topical antifungal drugs for treating acute oral candidiasis. The research focuses on the pharmaco-technological control of certain bio-mucoadhesive tablets containing miconazole nitrate, formulas developed and prepared by the authors based on the original formulas. The analyzed parameters were: macroscopic aspect, physical-chemical (pH) and pharmacotechnical properties (hardness, friability, mass uniformity, in vitro disintegration).The used methods are described in literature, most of them included in the Romanian and European Pharmacopoeia. The obtained results allow us to conclude that of the five original formulas, two (formulas IV and V) meet the criteria for oral mucosa drug by their tolerance (pH 5.77 to 5.84) and retention time (65-90 min.), the intimate contact of the tablet with the oral mucosa determining a high concentration of active substance. PMID:24505925

Birsan, Magdalena; Popovici, Iuliana; Palade, Laura; Cojocaru, Ileana

2013-01-01

207

Effects of repeated tramadol and morphine administration on psychomotor and cognitive performance in opioid-dependent volunteers  

PubMed Central

Tramadol is an atypical, mixed mechanism analgesic used to treat moderate to severe pain. Based on evidence that tramadol has relatively low abuse potential and can relieve opioid withdrawal, tramadol may be useful for treating opioid dependence. The purpose of this study was to assess the performance side-effect profile of tramadol. Nine opioid-dependent volunteers completed a performance battery following 5–7 days of subcutaneous morphine (15 mg, 4 times/day) and two doses of oral tramadol (50, 200 mg, 4 times/day) in a within subject cross-over design. Morphine was always the first condition, and the order of the two tramadol doses was randomized and double blind. Performance was significantly worse in the morphine condition relative to one or both tramadol doses on measures of psychomotor speed/coordination (circular lights task), psychomotor speed/pattern recognition (DSST speed measure) and psychomotor speed/set shifting (trail-making tasks). There were no significant differences among conditions in DSST accuracy, simple reaction time, divided attention, working memory, episodic memory, metamemory, or time estimation. Neither tramadol dose was associated with worse performance than morphine on any measure. Although practice sessions were conducted prior to the first session to reduce order effects, the possibility that residual practice effects contributed to the differences between tramadol and morphine cannot be ruled out. The high tramadol dose produced worse performance than the low dose only on the balance measure. These findings suggest that tramadol is generally a safe medication with respect to cognitive and psychomotor measures and support tramadol’s further evaluation as an opioid dependence treatment. PMID:20538418

Mintzer, Miriam Z.; Lanier, Ryan K.; Lofwall, Michelle R.; Bigelow, George E.; Strain, Eric C.

2010-01-01

208

Intrathecal morphine for analgesia in children undergoing selective dorsal rhizotomy  

Microsoft Academic Search

Selective dorsal root rhizotomy is performed for relief of spasticity in children with cerebral palsy. Postoperative pain relief can be provided by intrathecal morphine administered at the time of the procedure. We sought to define an optimal dose of intrathecal morphine in children undergoing selective rhizotomy, through a randomized, double-blinded prospective trial. After institutional approval and parental written informed consent,

Teresa E. Dews; Armin Schubert; Arno Fried; Zeyd Ebrahim; Kenneth Oswalt; Lata Paranandi

1996-01-01

209

Morphine and alternative opioids in cancer pain: the EAPC recommendations  

Microsoft Academic Search

An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical

G W Hanks; F de Conno; N Cherny; M Hanna; E Kalso; H J McQuay; S Mercadante; J Meynadier; P Poulain; C Ripamonti; L Radbruch; J Roca i Casas; J Sawe; R G Twycross; V Ventafridda

2001-01-01

210

Morphine-Induced Ventilatory Failure After Spinal Cord Compression  

Microsoft Academic Search

We describe a patient who required large doses of parenteral morphine for severe pain secondary to epidural spinal cord compression caused by metastatic cancer. The pain improved suddenly after neurological progression to a complete cord compression. Shortly afterwards, the patient developed acute respiratory depression caused by an apparent relative overdose of morphine. Our hypothesis is that the cord compression relieved

Fernando Quevedo; Declan Walsh

1999-01-01

211

Novel receptor mechanisms for heroin and morphine-6?-glucuronide analgesia  

Microsoft Academic Search

The rapid metabolism of heroin to 6-acetylmorphine and its slower conversion to morphine has led many to believe that heroin and morphine act through the same receptors and that the differences between them are due to their pharmacokinetics. We now present evidence strongly implying that heroin and two potent mu drugs, fentanyl and etonitazine, act through a unique receptor mechanism

Grace C. Rossi; George P. Brown; Liza Leventhal; Ke Yang; Gavril W. Pasternak

1996-01-01

212

Morphine reduces local cytokine expression and neutrophil infiltration after incision  

Microsoft Academic Search

BACKGROUND: Inflammation and nociceptive sensitization are hallmarks of tissue surrounding surgical incisions. Recent studies demonstrate that several cytokines may participate in the enhancement of nociception near these wounds. Since opioids like morphine interact with neutrophils and other immunocytes, it is possible that morphine exerts some of its antinociceptive action after surgical incision by altering the vigor of the inflammatory response.

J David Clark; Xiaoyou Shi; Xiangqi Li; Yanli Qiao; DeYong Liang; Martin S Angst; David C Yeomans

2007-01-01

213

Morphine as a Potential Oxidative Stress-Causing Agent  

PubMed Central

Morphine exhibits important pharmacological effects for which it has been used in medical practice for quite a long time. However, it has a high addictive potential and can be abused. Long-term use of this drug can be connected with some pathological consequences including neurotoxicity and neuronal dysfunction, hepatotoxicity, kidney dysfunction, oxidative stress and apoptosis. Therefore, most studies examining the impact of morphine have been aimed at determining the effects induced by chronic morphine exposure in the brain, liver, cardiovascular system and macrophages. It appears that different tissues may respond to morphine diversely and are distinctly susceptible to oxidative stress and subsequent oxidative damage of biomolecules. Importantly, production of reactive oxygen/nitrogen species induced by morphine, which have been observed under different experimental conditions, can contribute to some pathological processes, degenerative diseases and organ dysfunctions occurring in morphine abusers or morphine-treated patients. This review attempts to provide insights into the possible relationship between morphine actions and oxidative stress. PMID:24376392

Skrabalova, Jitka; Drastichova, Zdenka; Novotny, Jiri

2013-01-01

214

CSF distribution of morphine, methadone and sucrose after intrathecal injection.  

PubMed

The lumbar to cisternal CSF distribution of morphine and methadone were compared to C-14 sucrose, a standard marker of CSF bulk flow, after lumbar subarachnoid injections in a sheep preparation. Morphine appeared and peaked simultaneously with C-14 sucrose in cisternal CSF at 90 to 190 minutes. The mean peak cisternal CSF morphine concentrations were sustained for 30-40 minutes, and averaged 148 ng/ml, representing 0.3% of the administered dose. Methadone was not detectable in cisternal CSF up to 240-300 minutes after lumbar subarachnoid administration. The C-14 sucrose/morphine ratio was increased an average of 6.7 times in cisternal CSF as compared to the ratio of the two compounds injected into the lumbar subarachnoid space. These studies demonstrate that morphine, a hydrophilic opioid, given intrathecally moves rostrally and appears in cisternal CSF by bulk flow. Furthermore the rostral redistribution of morphine is associated with the clearance of morphine from CSF. Methadone, a lipophilic opioid, appears to be completely cleared from CSF before it reaches the cisterna magna. These pharmacokinetic studies support a contribution of supraspinal sites to the analgesic and adverse effects produced by morphine given by spinal routes of administration. In contrast methadone appears to exert its effects predominantly at spinal sites. PMID:3839885

Payne, R; Inturrisi, C E

1985-09-23

215

BDNF is a Negative Modulator of Morphine Action  

PubMed Central

Summary Brain-derived neurotrophic factor (BDNF) is a key positive regulator of neural plasticity, promoting for example, the actions of stimulant drugs of abuse such as cocaine. We discovered a surprising opposite role for BDNF in countering responses to chronic morphine. The suppression of BDNF in the ventral tegmental area (VTA) enhanced the ability of morphine to increase dopamine (DA) neuron excitability and promote reward. In contrast, optical stimulation of VTA DA terminals in nucleus accumbens (NAc) completely reversed the suppressive effect of BDNF on morphine reward. Furthermore, we identified numerous genes in NAc, a major target region of VTA DA neurons, whose regulation by BDNF in the context of chronic morphine exposure mediated this counteractive function. These findings provide insight into the molecular basis of morphine-induced neuroadaptations in the brain’s reward circuitry. PMID:23042896

Koo, Ja Wook; Mazei-Robison, Michelle S.; Chaudhury, Dipesh; Juarez, Barbara; LaPlant, Quincey; Ferguson, Deveroux; Feng, Jian; Sun, Haosheng; Scobie, Kimberly N.; Damez-Werno, Diane; Crumiller, Marshall; Ohnishi, Yoshinori N.; Ohnishi, Yoko H.; Mouzon, Ezekiell; Dietz, David M.; Lobo, Mary Kay; Neve, Rachael L.; Russo, Scott J.; Han, Ming-Hu; Nestler, Eric J.

2013-01-01

216

A study on maize proteins as a potential new tablet excipient.  

PubMed

This investigation has examined the use of zein proteins from maize as the major component in oral controlled-release tablets, such formulations often being required to improve patient compliance. Tablets containing ground zein proteins, calcium hydrogen orthophosphate, polyvinyl pyrrolidone, theophylline and magnesium stearate were produced by wet granulation and compression on a single station tablet press and were compared to directly compressed tablets based on zein proteins, calcium hydrogen orthophosphate and theophylline. Non invasive techniques such as Fourier Transform infrared spectroscopy and Fourier Transform Raman spectroscopy were employed to investigate any changes in the secondary structure of zein proteins during tablet production. Random coils, alpha helices and beta sheets predominated and their relative content remained unaffected during grinding, wet granulation and compression, indicating that formulations based on zeins will be robust, i.e. insensitive to minor changes in the production conditions. Drug release from the tablets was studied using a standard pharmacopoeial dissolution test. Dissolution profiles in water, 0.1M HCl (pH=1) and phosphate buffer (pH=6.8) show that only a limited amount of theophylline was released after 4.5h, suggesting that zein proteins could act as a potential vehicle for oral controlled drug release. Analysis of the theophylline release profiles using the Peppas and Sahlin model reveals that diffusion and polymer relaxation occurred in acidic (pH=1) and buffered (pH=6.8) conditions for wet granulated tablets, whereas diffusion was predominant in directly compressed tablets. In conclusion, the present study has shown that zeins can be successfully used as a pharmaceutical excipient, and in particular as a matrix in monolithic controlled release tablets. PMID:18294824

Georget, Dominique M R; Barker, Susan A; Belton, Peter S

2008-06-01

217

Efficiency of postoperative pain management after gynecologic oncological surgeries with the use of morphine + acetaminophen + ketoprofen versus morphine + metamizol + ketoprofen.  

PubMed

Surgical treatment used in gynecological oncology involves acute postoperative pain which requires efficient treatment. This study covered a group of 128 patients who were randomly divided into two groups. In the postoperative period patients in group I were administered morphine subcutaneously, acetaminophen intravenously and naproxen per rectum. The pain intensity level was checked by means of the pain intensity numeric rating scale (NRS). In the instances of pain rated at 5 or more, patients were additionally administered ketoprofen intravenously. Patients in group II were administered morphine, naproxen, and metamizole instead of acetaminophen and ketoprofen additionally. In group I after the administration of morphine and acetaminophen 22 patients (34.37%) needed additional doses of ketoprofen. In group II 33 women (51.56%) required ketoprofen after the administration of morphine and metamizole (N1 = 22 vs N2 = 33, p < 0.05). The use of metamizol with morphine (without ketoprofen) gave worse analgesic results than acetaminophen with morphine, but the combination of morphine, acetaminophen and ketoprofen or morphine, metamizol and ketoprofen gave satisfactory analgesic results. PMID:21614906

Samulak, D; Michalska, M; Gaca, M; Wilczak, M; Mojs, E; Chuchracki, M

2011-01-01

218

PolyMorphine: an innovative biodegradable polymer drug for extended pain relief  

PubMed Central

Morphine, a potent narcotic analgesic used for the treatment of acute and chronic pain, was chemically incorporated into a poly(anhydride-ester) backbone. The polymer termed “PolyMorphine”, was designed to degrade hydrolytically releasing morphine in a controlled manner to ultimately provide analgesia for an extended time period. PolyMorphine was synthesized via melt-condensation polymerization and its structure was characterized using proton and carbon nuclear magnetic resonance spectroscopies, and infrared spectroscopy. The weight-average molecular weight and the thermal properties were determined. The hydrolytic degradation pathway of the polymer was determined by in vitro studies, showing that free morphine is released. In vitro cytocompatibility studies demonstrated that PolyMorphine is non-cytotoxic towards fibroblasts. In vivo studies using mice showed that PolyMorphine provides analgesia for 3 days, 20 times the analgesic window of free morphine. The animals retained full responsiveness to morphine after being subjected to an acute morphine challenge. PMID:22877734

Rosario-Meléndez, Roselin; Harris, Carolyn L.; Delgado-Rivera, Roberto; Yu, Lei; Uhrich, Kathryn E.

2012-01-01

219

Postoperative morphine requirements, nausea and vomiting following anaesthesia for tonsillectomy. Comparison of intravenous morphine and non-opioid analgesic techniques.  

PubMed

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be as effective as opioid analgesia following tonsillectomy in children. Opioids are still frequently used but tonsillectomy is associated with a high incidence of vomiting. This study has attempted to assess postoperative analgesic consumption and nausea and vomiting after general anaesthesia for tonsillectomy using either paracetamol premedication, paracetamol plus a NSAID or intravenous morphine to provide postoperative analgesia. Some children required a rescue dose of morphine in the recovery room, including some who had received intravenous morphine at induction. Least supplementary morphine was required by those who had received paracetamol plus ketorolac. Postoperative nausea and vomiting was significantly less in the two groups which were not given intraoperative morphine. The number of vomiting incidents was also much less. We conclude that the preoperative administration of paracetamol alone provides satisfactory analgesia in many children but that supplementary analgesia is still required for some. PMID:7489439

Mather, S J; Peutrell, J M

1995-01-01

220

Tablet PCs: The Write Approach  

ERIC Educational Resources Information Center

This article discusses the transforming effects of tablet PCs in the classroom. As 1-to-1 computing becomes the goal on K-12 campuses, school districts are turning to this newer, pen-based technology. Saint Mary's School's new Lenovo ThinkPad X41 tablet PCs had transformed the way Saint Mary's teachers did their jobs. Teachers created outlines for…

Milner, Jacob

2006-01-01

221

Alkaloids; Strychnine, Codeine, Heroin, and Morphine  

NSDL National Science Digital Library

The featured molecules this month come from the article "The Conversion of Carboxylic Acids to Ketones: A Repeated Discovery" by John W. Nicholson and Alan D. Wilson. The authors describe the repeated discovery of this reaction and illustrate its central role in Woodward's total synthesis of strychnine. Strychnine is a member of a large class of nitrogen heterocycles known as alkaloids, a name derived from the fact that all produce basic solutions in water. Other well-known members of this class of compounds, all of which are pharmacologically active, are nicotine, atropine (deadly nightshade), quinine, lysergic acid, cocaine, and the three structurally similar compounds codeine, heroin, and morphine.

222

Regional differences of morphine on neuronal impulse activity in cervically transected rats  

E-print Network

the abstinence syndrome. In a different study (Wei, 1974) the inhibitory effects of morphine on wet shake behavior were shown to depend on the periaqueductal-fourth ventricle area, medial preoptic area, and the locus coeruleus. Bilateral lesions... cells were morphine depressed, but the cells in the ventro-median nucleus were morphine excitable. Jacobs and Lomax (1972) found that morphine depressed cingulate cortex cells. Buxbaum and Pamplin (1975) reported that morphine decreased neuronal...

Mallari, Clinton

1977-01-01

223

Morphine tolerance offers protection from radiogenic performance deficits  

SciTech Connect

When rats are exposed to a sufficiently large dose of ionizing radiation they exhibit lethargy, hypokinesia, and deficits in performance. These and other behavioral changes parallel those often observed in this species after a large dose of morphine. Since the release of endogenous opiates has been implicated in some stress reactions, we sought to determine if they might play a part in radiogenic behavioral deficits. Rats were trained to criterion on a signaled avoidance task. Some subjects were then implanted with a pellet containing 75 mg of morphine. Other animals received placebo implants. Over a number of days, morphine tolerance was evaluated by measurement of body temperature changes. Prior to 2500 rad /sup 60/Co exposure or sham irradiation, morphine (or placebo) pellets were removed. Twenty-four hours later rats were retested to assess their performance on the avoidance task. Morphine-tolerant subjects performed significantly better than the irradiated placebo-implanted group and no differently than morphine-tolerant/sham-irradiated animals. Morphine tolerance seems to provide a degree of behavioral radiation resistance. These data are consistent with the hypothesis that endogenous opiate hyperexcretion may play some part in the behavioral deficits often observed after irradiation.

Mickley, G.A. (U.S. Air Force Acamemy, Co); Stevens, K.E.; Burrows, J.M.; White, G.A.; Gibbs, G.L.

1983-02-01

224

Endogenous Cholinergic Neurotransmission Contributes to Behavioral Sensitization to Morphine  

PubMed Central

Neuroplasticity in the mesolimbic dopaminergic system is critical for behavioral adaptations associated with opioid reward and addiction. These processes may be influenced by cholinergic transmission arising from the laterodorsal tegmental nucleus (LDTg), a main source of acetylcholine to mesolimbic dopaminergic neurons. To examine this possibility we asked if chronic systemic morphine administration affects expression of genes in ventral and ventrolateral periaqueductal gray at the level of the LDTg using rtPCR. Specifically, we examined gene expression changes in the area of interest using Neurotransmitters and Receptors PCR array between chronic morphine and saline control groups. Analysis suggested that chronic morphine administration led to changes in expression of genes associated, in part, with cholinergic neurotransmission. Furthermore, using a quantitative immunofluorescent technique, we found that chronic morphine treatment produced a significant increase in immunolabeling of the cholinergic marker (vesicular acetylcholine transporter) in neurons of the LDTg. Finally, systemic administration of the nonselective and noncompetitive neuronal nicotinic antagonist mecamylamine (0.5 or 2 mg/kg) dose-dependently blocked the expression, and to a lesser extent the development, of locomotor sensitization. The same treatment had no effect on acute morphine antinociception, antinociceptive tolerance or dependence to chronic morphine. Taken together, the results suggest that endogenous nicotinic cholinergic neurotransmission selectively contributes to behavioral sensitization to morphine and this process may, in part, involve cholinergic neurons within the LDTg. PMID:25647082

Bajic, Dusica; Soiza-Reilly, Mariano; Spalding, Allegra L.; Berde, Charles B.; Commons, Kathryn G.

2015-01-01

225

Effects of secretin on acute and chronic effects of morphine.  

PubMed

The effects of intracerebroventricularly (ICV) administered secretin on the analgesic, tolerance-inducing, and dependence-inducing actions of morphine were investigated, in adult, male CFLP mice. Secretin administered doses ICV did not itself affect pain sensitivity in a heat-radiant tail flick test. However, it depressed the acute nociceptive effect of a single subcutaneous (SC) dose of morphine (4 mg/kg) after ICV (1 or 10 ng/animal) secretin administration. A dose of 10 ng secretin facilitated the development of acute morphine tolerance. On the other hand, none of the doses applied had any influence on chronic morphine tolerance, where animals were implanted SC with a morphine- containing pellet and the pain sensitivity was measured 3 days later. Morphine withdrawal signs were also evaluated by injecting naloxone. In a 100-ng dose, secretin increased the latency of the withdrawal jumping response; the peptide did not modify the other abstinence signs. These data suggest that central secretin administration can modify the analgesic effect of morphine. PMID:7667370

Babarczy, E; Szabó, G; Telegdy, G

1995-01-01

226

Mechanistic basis of altered morphine disposition in nonalcoholic steatohepatitis.  

PubMed

Morphine is metabolized in humans to morphine-3-glucuronide (M3G) and the pharmacologically active morphine-6-glucuronide (M6G). The hepatobiliary disposition of both metabolites relies upon multidrug resistance-associated proteins Mrp3 and Mrp2, located on the sinusoidal and canalicular membrane, respectively. Nonalcoholic steatohepatitis (NASH), the severe stage of nonalcoholic fatty liver disease, alters xenobiotic metabolizing enzyme and transporter function. The purpose of this study was to determine whether NASH contributes to the large interindividual variability and postoperative adverse events associated with morphine therapy. Male Sprague-Dawley rats were fed a control diet or a methionine- and choline-deficient diet to induce NASH. Radiolabeled morphine (2.5 mg/kg, 30 µCi/kg) was administered intravenously, and plasma and bile (0-150 or 0-240 minutes), liver and kidney, and cumulative urine were analyzed for morphine and M3G. The antinociceptive response to M6G (5 mg/kg) was assessed (0-12 hours) after direct intraperitoneal administration since rats do not produce M6G. NASH caused a net decrease in morphine concentrations in the bile and plasma and a net increase in the M3G/morphine plasma area under the concentration-time curve ratio, consistent with upregulation of UDP-glucuronosyltransferase Ugt2b1. Despite increased systemic exposure to M3G, NASH resulted in decreased biliary excretion and hepatic accumulation of M3G. This shift toward systemic retention is consistent with the mislocalization of canalicular Mrp2 and increased expression of sinusoidal Mrp3 in NASH and may correlate to increased antinociception by M6G. Increased metabolism and altered transporter regulation in NASH provide a mechanistic basis for interindividual variability in morphine disposition that may lead to opioid-related toxicity. PMID:25512370

Dzierlenga, Anika L; Clarke, John D; Hargraves, Tiffanie L; Ainslie, Garrett R; Vanderah, Todd W; Paine, Mary F; Cherrington, Nathan J

2015-03-01

227

Morphine enhances doxorubicin-induced cardiotoxicity in the rat.  

PubMed

Interventions to reduce the cardiotoxicity of doxorubicin are clinically relevant. Pharmacological preconditioning mimicking ischemic preconditioning has been demonstrated with morphine and represents an acceptable clinical intervention. The purpose of this study was to examine if pretreatment in vivo with morphine could reduce doxorubicin-induced cardiotoxicity ex vivo in a rat model. Wistar rats were divided into six groups and pretreated with an intraperitoneal (i.p.) injection of 3 or 10 mg/kg morphine, 1 mg/kg naloxone and saline, 1 mg/kg naloxone and 3 mg/kg morphine or saline, 60 min before excision of the heart. Biochemical indices such as troponin T (TnT) and hydrogen peroxide (H2O2) in effluate were measured together with physiological parameters in Langendorff hearts before and after doxorubicin infusion (2 mg/mL 0.05 mL/min for 45 min). Myocardial content of doxorubicin was measured at the end of infusion. Pretreatment with morphine, irrespective of dosage, produced a significant loss in left ventricular-developed pressure and an increase of TnT and H2O2 in effluate before doxorubicin infusion (p < 0.05). Morphine also produced a significant increase in left ventricular end-diastolic pressure and an increase of TnT and H2O2 in effluate (p < 0.05) at the end of doxorubicin infusion. Naloxone, a non-selective opioid receptor antagonist, abolished the effects of morphine both before and after doxorubicin infusion. Morphine, irrespective of dosage, increased myocardial content of doxorubicin compared to pretreatment with saline (p < 0.05). Pretreatment with morphine is associated with a cardiodepressive effect and enhances cardiotoxicity of doxorubicin measured by increased myocardial accumulation of doxorubicin and physiological and biochemical indices. The negative effects observed in our rat model are abolished by naloxone. PMID:24531975

Hole, Lisa Drange; Larsen, Terje Hjalmar; Fossan, Kjell Ove; Limé, Fredrik; Schjøtt, Jan

2014-09-01

228

Morphine dependence and withdrawal induced changes in cholinergic signaling  

PubMed Central

Cholinergic signaling is thought to be involved in morphine dependence and withdrawal, but the specific mechanisms involved remain unclear. The current study aimed to identify alterations in the cholinergic system that may contribute to the development of morphine dependence and withdrawal. Acetylcholinesterase (AChE) activity and [3H]-epibatidine binding were evaluated in order to determine if morphine dependence and withdrawal induces alterations in cholinergic signaling or expression of high affinity nicotinic acetylcholine receptors (nAChRs) in the midbrain (MB), medial habenula (MHb) and interpeduncular nucleus (IPN). The effect of cholinergic signaling through nAChRs on morphine-withdrawal induced jumping behavior was then determined. Lastly, the contribution of ?4-containing nAChRs receptors in the MHb to morphine-withdrawal induced jumping behavior and neuronal activity as indicated by c-fos expression was assessed. Chronic morphine administration decreased AChE activity in MB and MHb, an effect that was no longer present following precipitated withdrawal. Morphine dependent mice showed increased nicotinic acetylcholine receptor (nAChR) levels in MB. Further, nicotine (0.4 mg/kg) and lobeline (3 mg/kg) decreased jumping behavior while mecamylamine (1 mg/kg) had no effect. Knock-down of ?4 subunit-containing nAChRs in the MHb attenuated c-fos activation, but did not decrease morphine withdrawal-induced jumping. Thus, morphine withdrawal induces cholinergic signaling in the MHb, but this does not appear to be responsible for the effects of cholinergic drugs on somatic signs of opiate withdrawal, as measured by jumping behavior. PMID:23651795

Neugebauer, Nichole M.; Einstein, Emily B.; Lopez, Maria B.; McClure-Begley, Tristan D.; Mineur, Yann S.; Picciotto, Marina R.

2013-01-01

229

Recent Advances in the Synthesis of Morphine and Related Alkaloids  

NASA Astrophysics Data System (ADS)

Morphine, an alkaloid isolated from the opium poppy, has been widely used as an analgesic, and has been a fascinating synthetic target of organic chemists. After the first total synthesis reported in 1952, a number of synthetic studies toward morphine have been reported, and findings obtained in such studies have greatly contributed to the progress of synthetic organic chemistry as well as medicinal chemistry. This review provides an overview of recent studies toward the total synthesis of morphine and related alkaloids. Work reported in the literature since 2004 will be reviewed.

Chida, Noritaka

230

Effects of morphine and naloxone on feline colonic transit  

SciTech Connect

The effects of endogenous and exogenous opioid substances on feline colonic transit were evaluated using colonic transit scintigraphy. Naloxone accelerated emptying of the cecum and ascending colon, and filling of the transverse colon. Endogenous opioid peptides thus appear to play a significant role in the regulation of colonic transit. At a moderate dose of morphine cecum and ascending colon transit was accelerated, while at a larger dose morphine had no effect. Since naloxone, a relatively nonspecific opioid antagonist, and morphine, a principally mu opioid receptor agonist, both accelerate proximal colonic transit, a decelerating role for at least one of the other opioid receptors is inferred.

Krevsky, B.; Libster, B.; Maurer, A.H.; Chase, B.J.; Fisher, R.S.

1989-01-01

231

Cholescintigraphy in acute cholecystitis: use of intravenous morphine  

SciTech Connect

Conventional cholescintigraphy (60 patients) and a modified protocol (59 patients) were compared in 74 females and 45 males with acute cholecystitis. In the modified protocol, intravenous morphine was administered whenever the gallbladder was not seen 40 minutes after injection of Tc-99m-pyroxylidene-glutamate. Accuracy was 98% with morphine, compared with 88% for the conventional protocol; specificity improved from 83% to 100% with no loss of sensitivity. Low doses of morphine are well tolerated and can result in a highly accurate diagnosis of acute cholecystitis without the need for delayed imaging.

Choy, D.; Shi, E.C.; McLean, R.G.; Hoschl, R.; Murray, I.P.C.; Ham, J.M.

1984-04-01

232

Development and evaluation of glyburide fast dissolving tablets using solid dispersion technique.  

PubMed

Glyburide is a poorly water-soluble oral hypoglycemic agent, with problems of variable bioavailability and bio-inequivalence related to its poor water-solubility. This work investigated the possibility of developing glyburide tablets, allowing fast, reproducible, and complete drug dissolution, by using drug solid dispersion in polyethylene glycol. Phase-solubility studies were performed to investigate the drug-carrier interactions in solution, whereas differential scanning calorimetry, X-ray powder diffraction, and infrared spectroscopy were used to characterize the solid state of solid dispersions. The effects of several variables related to both solid dispersion preparation (cofusion or coevaporation technique, drug-to-carrier ratio, polyethylene glycol molecular weight) and tablet production (direct compression or previous wet-granulation, tablet hardness, drug, and solid dispersion particle size) on drug dissolution behavior were investigated. Tablets obtained by direct compression, with a hardness of 7-9 Kp, and containing larger sized solid dispersions (20-35 mesh, i.e., 850-500 microm) of micronized glyburide in polyethylene glycol 6000 prepared by the cofusion method gave the best results, with a 135% increase in drug dissolution efficiency at 60 min in comparison with a reference tablet formulation containing the pure micronized drug. Moreover, the glyburide dissolution profile from the newly developed tablets was clearly better than those from various commercial tablets at the same drug dosage. PMID:15244088

Valleri, M; Mura, P; Maestrelli, F; Cirri, M; Ballerini, R

2004-05-01

233

Vardenafil orodispersible tablet.  

PubMed

Vardenafil orodispersible tablet (ODT) is a supralingual formulation of vardenafil that is available for the on-demand treatment of erectile dysfunction. The pharmacokinetics of vardenafil ODT are not equivalent to those of the vardenafil film-coated tablet in that the ODT formulation provides consistently greater vardenafil systemic exposure. Therefore, the two formulations are not interchangeable. The efficacy of on-demand vardenafil ODT 10 mg was established in the POTENT I and II studies, which were 6-week, randomized, double-blind, multinational trials in men with erectile dysfunction of at least 6 months duration. In both trials, vardenafil ODT improved erectile function significantly more than placebo, as indicated by International Index of Erectile Function-Erectile Function subscale scores at week 12 and overall erection success rates during treatment according to responses to questions 2 and 3 of the Sexual Encounter Profile (coprimary endpoints). In a pooled analysis of both trials, vardenafil ODT improved erectile function regardless of age, severity of erectile dysfunction at baseline or the presence or absence of underlying medical conditions. Vardenafil ODT was generally well tolerated in clinical trials, including in men aged ?65 years, and adverse events were mostly mild or moderate in severity. PMID:22191797

Sanford, Mark

2012-01-01

234

Formulation, Characterization and Physicochemical Evaluation of Ranitidine Effervescent Tablets  

PubMed Central

Purpose: The aim of this study was to design, formulate and physicochemically evaluate effervescent ranitidine hydrochloride (HCl) tablets since they are easily administered while the elderly and children sometimes have difficulties in swallowing oral dosage forms. Methods: Effervescent ranitidine HCl tablets were prepared in a dosage of 300 mg by fusion and direct compression methods. The powder blend and granule mixture were evaluated for various pre-compression characteristics, such as angle of repose, compressibility index, mean particle size and Hausner's ratio. The tablets were evaluated for post-compression features including weight variation, hardness, friability, drug content, dissolution time, carbon dioxide content, effervescence time, pH, content uniformity and water content. Effervescent systems with appropriate pre and post-compression qualities dissolved rapidly in water were selected as the best formulations. Results: The results showed that the flowability of fusion method is more than that of direct compression and the F5 and F6 formulations of 300 mg tablets were selected as the best formulations because of their physicochemical characteristics. Conclusion: In this study, citric acid, sodium bicarbonate and sweeteners (including mannitol, sucrose and aspartame) were selected. Aspartame, mint and orange flavors were more effective for masking the bitter taste of ranitidine. The fusion method is the best alternative in terms of physicochemical and physical properties. PMID:24312854

Aslani, Abolfazl; Jahangiri, Hajar

2013-01-01

235

Microporous bilayer osmotic tablet for colon-specific delivery.  

PubMed

Microporous bilayer osmotic tablet bearing dicyclomine hydrochloride and diclofenac potassium was developed using a new oral drug delivery system for colon targeting. The tablets were coated with microporous semipermeable membrane and enteric polymer using conventional pan-coating process. The developed microporous bilayer osmotic pump tablet (OPT) did not require laser drilling to form the drug delivery orifice. The colon-specific biodegradation of pectin could form in situ delivery pores for drug release. The effect of formulation variables like inclusion of osmogen, amount of HPMC and NaCMC in core, amount of pore former in semipermeable membrane was studied. Scanning electron microscopic photographs showed formation of in situ delivery pores after predetermined time of coming in contact with dissolution medium. The number of pores was dependent on the amount of the pore former in the semipermeable membrane. In vitro dissolution results indicated that system showed acid-resistant, timed release and was able to deliver drug at an approximate zero order up to 24h. The developed tablets could be effectively used for colon-specific drug delivery to treat IBS. PMID:21255646

Chaudhary, Anil; Tiwari, Neha; Jain, Vikas; Singh, Ranjit

2011-05-01

236

Detection of morphine-3-sulfate and morphine-6-sulfate in human urine and plasma, and formation in liver cytosol.  

PubMed

Morphine is still the mainstay in treatment of severe pain and is metabolized in the liver mainly by glucuronidation, partly to the pharmacologically active morphine-6-glucuronide (M6G). The sulfation pathway has attracted much less attention but may also form active metabolites. The aim of the present study was to study two sulfate metabolites of morphine in humans. Urine and plasma from newborns, adult heroin addicts, and terminal cancer patients was analyzed for the presence of morphine-3-sulfate (M3S) and morphine-6-sulfate (M6S) by a new liquid chromatography - tandem mass spectrometry (LC-MS/MS) method. In addition, morphine sulfation was studied in vitro in human liver cytosol preparations. M3S was present in urine and plasma from all study groups although at lower concentrations than morphine-3-glucuronide (M3G). The plasma M3S/M3G ratio was 30 times higher in newborns than in adults indicating that the relative sulfation is more important at early stage of life. M6S was measurable in only one plasma sample from a newborn patient, and in one of the urine sample from the drug testing group. The incubation of morphine with liver cytosol extracts resulted in approximately equal rate of formation of both M3S and M6S. In conclusion, sulfation of morphine is catalyzed in human liver but this minor metabolic pathway probably lacks clinical significance. The M6S metabolite is formed at a low rate, making it undetectable in most individuals. PMID:25505615

Andersson, Maria; Björkhem-Bergman, Linda; Ekström, Lena; Bergqvist, Lena; Lagercrantz, Hugo; Rane, Anders; Beck, Olof

2014-12-01

237

Pharmacokinetics of the combination hydrochlorothiazide and bisoprolol tablet in Chinese healthy young male and female volunteers  

Microsoft Academic Search

The pharmacokinetics of bisoprolol\\/hydrochlorothiazide compound formulation (A: 2.5\\/6.25, B: 5\\/6.25, or C: 10\\/6.25 mg in each tablet) was studied after oral administration in Chinese healthy volunteers that was divided into 3 groups of 8 males and 8 females per group. Each subject was randomized to receive a single oral dose of the compound either A, B or C in a

Ke Xu; Chen Hui; Xu Rong; Wang Ping; Gu Shifen; Ru Lin; Zeng Fandian

238

Development, characterization and permeability assessment based on caco-2 monolayers of self-microemulsifying floating tablets of tetrahydrocurcumin.  

PubMed

Novel self-microemulsifying floating tablets were developed to enhance the dissolution and oral absorption of the poorly water-soluble tetrahydrocurcumin (THC). Their physicochemical properties and THC permeability across Caco-2 cell monolayers were assessed. The self-microemulsifying liquid containing THC was adsorbed onto colloidal silicon dioxide, mixed with HPMC, gas-generating agents (sodium bicarbonate and tartaric acid), lactose and silicified-microcrystalline cellulose and transformed into tablets by direct compression. The use of different types/concentrations of HPMC and sodium bicarbonate in tablet formulations had different effects on the floating characteristics and in vitro THC release. The optimum tablet formulation (F2) provided a short floating lag time (?23 s) together with a prolonged buoyancy (>12 h). About 72% of THC was released in 12 h with an emulsion droplet size in aqueous media of 33.9±1.0 nm while that of a self-microemulsifying liquid was 29.9±0.3 nm. The tablet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. The THC released from the self-microemulsifying liquid and tablet formulations provided an approximately three- to fivefold greater permeability across the Caco-2 cell monolayers than the unformulated THC and indicated an enhanced absorption of THC by the formulations. The self-microemulsifying floating tablet could provide a dosage form with the potential to improve the oral bioavailability of THC and other hydrophobic compounds. PMID:23319299

Sermkaew, Namfa; Wiwattanawongsa, Kamonthip; Ketjinda, Wichan; Wiwattanapatapee, Ruedeekorn

2013-03-01

239

Does chronic nociceptive stimulation alter the development of morphine tolerance?  

PubMed

Conflicting results exist concerning the issues of whether chronic nociceptive stimulation (a) increases or decreases the effectiveness of morphine analgesia, and (b) facilitates or inhibits the development of narcotic tolerance. We carried out a series of experiments with appropriate controls in order to examine these two issues and their possible relationship. In experiment 1, rats received complete Freund's adjuvant (CFA), a chronic nociceptor, injected into a single hind paw or anesthesia without injection, together with morphine or placebo pellets in a 2 x 2 study design. The data indicate that the presence of the chronic nociceptive stimulus significantly facilitated the development of tolerance to morphine analgesia as measured using tail-flick latency (TFL) testing. Experiment 2 was designed to compare the analgetic effectiveness of an acute injection of morphine in rats experiencing chronic nociceptive stimulation and in controls. CFA was injected in the right hindpaw, and nine days later TFLs were tested after morphine doses of 1 and 2 mg/kg s.c. The data obtained showed that chronic nociceptive stimulation significantly reduced the effectiveness of morphine at the 1 mg/kg dose. However, baseline TFLs appeared to be shorter in rats treated with CFA, suggesting that the decrease in morphine effectiveness could be due to a general increase in pain sensitivity. Therefore, a third experiment was performed, using a less intense thermal stimulus to prolong baseline TFLs and accentuate any potential differences. Sixteen rats either received CFA or served as controls. TFLs were then measured at baseline and one hour after a 0.5 mg/kg dose of morphine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7663975

Gutstein, H B; Trujillo, K A; Akil, H

1995-05-22

240

The Impact of Morphine After a Spinal Cord Injury  

PubMed Central

Nociceptive stimulation, at an intensity that elicits pain-related behavior, attenuates recovery of locomotor and bladder functions, and increases tissue loss after a contusion injury. These data imply that nociceptive input (e.g., from tissue damage) can enhance the loss of function after injury, and that potential clinical treatments, such pretreatment with an analgesic, may protect the damaged system from further secondary injury. The current study examined this hypothesis and showed that a potential treatment (morphine) did not have a protective effect. In fact, morphine appeared to exacerbate the effects of nociceptive stimulation. Experiment 1 showed that after spinal cord injury 20 mg/kg of systemic morphine was necessary to induce strong antinociception and block behavioral reactivity to shock treatment, a dose that was much higher than that needed for sham controls. In Experiment 2, contused rats were given one of three doses of morphine (Vehicle, 10, 20 mg/kg) prior to exposure to uncontrollable electrical stimulation or restraint alone. Despite decreasing nociceptive reactivity, morphine did not attenuate the long-term consequences of shock. Rats treated with morphine and shock had higher mortality rates, and displayed allodynic responses to innocuous sensory stimuli three weeks later. Independent of shock, morphine per se undermined recovery of sensory function. Rats treated with morphine alone also had significantly larger lesions than those treated with saline. These results suggest that nociceptive stimulation affects recovery despite a blockade of pain-elicited behavior. The results are clinically important because they suggest that opiate treatment may adversely affect the recovery of function after injury. PMID:17383022

Hook, Michelle A.; Liu, Grace T.; Washburn, Stephanie N.; Ferguson, Adam R.; Bopp, Anne C.; Huie, John R.; Grau, James W.

2007-01-01

241

Analgesic Efficacy of Morphine Applied Topically to Painful Ulcers  

Microsoft Academic Search

The analgesic effects of morphine applied topically to painful ulcers was assessed in a randomized, double-blind, placebo-controlled, crossover pilot study of five patients with painful sacral sores. Patients were treated for two days with either 10 mg morphine sulfate or placebo (water for injection) applied topically to the ulcer. After a two-day wash-out period, patients were crossed over for a

Giovambattista Zeppetella; James Paul; Maria D. C Ribeiro

2003-01-01

242

Persistent pain model reveals sex difference in morphine potency.  

PubMed

Central or systemic administration of agonists directed at the mu or delta opiate receptors generally produce a greater degree of analgesia in males than in females. To date, most studies examining sex-based differences in opioid analgesia have used acute noxious stimuli (i.e., tail-flick and hot plate test); thus the potential dimorphic response of centrally acting opiates in the alleviation of persistent inflammatory pain is not well established. In the present study, right hind paw withdrawal latency (PWL) to radiant thermal stimuli was measured in intact male and cycling female Sprague-Dawley rats before and after unilateral hind paw injection of the inflammatory agent complete Freund's adjuvant (CFA). Control animals received intraplantar injection of saline. Twenty four hours after CFA or saline injection, animals received either saline or morphine bisulfate (0.5-15 mg/kg sc). Separate groups of control or inflamed animals were tested on their responsiveness to morphine at 7, 14, and 21 days post-CFA or saline. No sex differences were noted for baseline PWLs, and females displayed slightly less thermal hyperalgesia at 24 h post-CFA. At all morphine doses administered, both the antihyperalgesic effects of morphine in the inflamed animals and the antinociceptive effects of morphine in control animals were significantly greater in males compared with females. Similarly, in males, the antihyperalgesic effects of morphine increased significantly at 7-21 days post-CFA; no significant shift in morphine potency was noted for females. These studies demonstrate sex-based differences in the effects of morphine on thermal hyperalgesia in a model of persistent inflammatory pain. PMID:16497818

Wang, Xiaoya; Traub, Richard J; Murphy, Anne Z

2006-08-01

243

Enhanced Immune Sensitivity to Stress Following Chronic Morphine Exposure  

Microsoft Academic Search

Chronic administration of escalating doses ofmorphine leads to neuroadaptive changes precipitating development of tolerance\\u000a to many of the acute effects of morphine, such as analgesia, activation of the hypothalamic–pituitary–adrenal (HPA) axis and\\u000a suppression of immune cell activities. Interestingly, morphine tolerance has also been shown to be accompanied by heightened\\u000a immunosuppressive effects of restraint stress using a rodent model. These observations

Kimberly A. Ballard; Trisha C. Pellegrino; Norma C. Alonzo; Alexandria L. Nugent; Barbara M. Bayer

2006-01-01

244

Endogenous morphine: up-to-date review 2011.  

PubMed

Positive evolutionary pressure has apparently preserved the ability to synthesize chemically authentic morphine, albeit in homeopathic concentrations, throughout animal phyla. Despite the establishment of a progressively rigorous and mechanistically focused historical literature extending from the mid 1970s to the mid 1980s that supported the expression of chemically authentic morphine by animal cellular and organ systems, prejudicial scepticism and early dismissal by scientists and clinicians most often obscured widespread acceptance of the biological importance and medical implications of endogenous morphine. The current critical paper presents and evaluates key recent coordinated studies in endogenous morphine research, highlighting those that have advanced our understanding of the functional roles of cognate alkaloid-selective ?(3) and ?(4) opiate receptors. We propose that the expression of endogenous morphine by animal and human cells is designed to mediate homeopathic regulation of metabolic activity via activation of cognate ?(3) and ?(4) receptors that serve as transductive conduits for shortcircuit Ca(++) fluxes. The implications of endogenous morphine coupling to nitric oxide regulation of mitochondrial function, with special reference to the cardiovascular system, are now formulated after many years of neglect. PMID:22578954

Stefano, G B; Ptá?ek, R; Kuželová, H; Kream, R M

2012-01-01

245

Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish  

PubMed Central

A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway. PMID:22205946

Khor, Beng-Siang; Amar Jamil, Mohd Fadzly; Adenan, Mohamad Ilham; Chong Shu-Chien, Alexander

2011-01-01

246

Acute morphine alters GABAergic transmission in the central amygdala during naloxone-precipitated morphine withdrawal: role of cyclic AMP  

PubMed Central

The central amygdala (CeA) plays an important role in opioid addiction. Therefore, we examined the effects of naloxone-precipitated morphine withdrawal (WD) on GABAergic transmission in rat CeA neurons using whole-cell recordings with naloxone in the bath. The basal frequency of miniature inhibitory postsynaptic currents (mIPSCs) increased in CeA neurons from WD compared to placebo rats. Acute morphine (10 ? M) had mixed effects (?20% change from baseline) on mIPSCs in placebo and WD rats. In most CeA neurons (64%) from placebo rats, morphine significantly decreased mIPSC frequency and amplitude. In 32% of placebo neurons, morphine significantly increased mIPSC amplitudes but had no effect on mIPSC frequency. In WD rats, acute morphine significantly increased mIPSC frequency but had no effect on mIPSC amplitude in 41% of CeA neurons. In 45% of cells, acute morphine significantly decreased mIPSC frequency and amplitude. Pre-treatment with the cyclic AMP inhibitor (R)-adenosine, cyclic 3',5'-(hydrogenphosphorothioate) triethylammonium (RP), prevented acute morphine-induced potentiation of mIPSCs. Pre-treatment of slices with the Gi/o G-protein subunit inhibitor pertussis toxin (PTX) did not prevent the acute morphine-induced enhancement or inhibition of mIPSCs. PTX and RP decreased basal mIPSC frequencies and amplitudes only in WD rats. The results suggest that inhibition of GABAergic transmission in the CeA by acute morphine is mediated by PTX-insensitive mechanisms, although PTX-sensitive mechanisms cannot be ruled out for non-morphine responsive cells; by contrast, potentiation of GABAergic transmission is mediated by activated cAMP signaling that also mediates the increased basal GABAergic transmission in WD rats. Our data indicate that during the acute phase of WD, the CeA opioid and GABAergic systems undergo neuroadaptative changes conditioned by a previous chronic morphine exposure and dependence. PMID:24926240

Bajo, Michal; Madamba, Samuel G.; Roberto, Marisa; Siggins, George R.

2014-01-01

247

Behavioral effects of fatty acid amide hydrolase inhibition on morphine withdrawal symptoms.  

PubMed

Chronic morphine exposure causes tolerance and dependence. The cessation of morphine consumption induces a withdrawal syndrome that may involve cannabinoids and is characterized by undesirable psychological and physical signs. The present study examined whether augmentation of the endocannabinoid system by inhibition of fatty acid amide hydrolase could suppress the morphine withdrawal syndrome in morphine-addicted rats. Morphine dependency was induced by 7 consecutive days of morphine injection. The morphine-addicted rats received URB597 (1, 0.5, 0.3, 0.1, 0.03 mg/kg), a fatty acid amide hydrolase inhibitor, before the precipitation of morphine withdrawal syndromes by naloxone. Withdrawal symptoms including jumping, teeth chattering, paw tremor, wet dog shakes, face grooming, penis licking, standing, rearing, sniffing and percent of weight loss were recorded during 30 min after naloxone injection. The results showed that the morphine withdrawal precipitated rats had significantly more withdrawal symptoms than naive control rats and the administration of URB597 (all doses except 0.03 mg/kg) reduced most of the morphine withdrawal symptoms. We conclude that the administration of URB597 modulated morphine withdrawal symptoms. This finding shows that endocannabinoids interact with the opioid system during the morphine withdrawal period and that potentiation of the endogenous cannabinoid system by URB597 may be a new target strategy for the management of morphine addiction. PMID:21763761

Shahidi, Siamak; Hasanein, Parisa

2011-08-10

248

Trans-stilbene oxide administration increased hepatic glucuronidation of morphine but decreased biliary excretion of morphine glucuronide in rats  

SciTech Connect

The effect of the inducing agent trans-stilbene oxide (TSO) on the metabolism and biliary excretion of (/sup 14/C)morphine was studied in the isolated in situ perfused rat liver. After administration of morphine by intraportal injection or by the segmented retrograde intrabiliary injection technique, the TSO-treated group showed a marked decrease in the biliary recovery of morphine as its glucuronide conjugate (morphine-3-glucuronide (MG)). However, recovery of MG in the venous outflow of the single pass perfusate was greatly increased. These findings suggested that TSO treatment enhanced the formation of MG from morphine and changed the primary route of hepatic elimination of MG. TSO treatment also decreased the excretion of morphine (as MG) in the bile of anesthetized renal-ligated rats. This decreased biliary function required several days to develop and appeared closely associated with the inductive effect of TSO. After i.v. administration of (/sup 14/C)MG itself, biliary recovery was also markedly decreased in TSO-treated rats. It is postulated that the effect of the TSO treatment led to either a decrease in canalicular transport of MG into bile or an increase in the efficiency of transfer of MG to the blood at the sinusoidal side of the hepatocyte. Regardless of the mechanism, the results indicate the need to study compartmentalization of drug transport and metabolism functions.

Fuhrman-Lane, C.; Fujimoto, J.M.

1982-09-01

249

Combined morphine-bupivacaine caudals for reconstructive penile surgery in children: systemic absorption of morphine and postoperative analgesia.  

PubMed

We wished to determine if the addition of a small dose of morphine (0.05 mg.kg-1) to a caudal solution of 0.25% bupivacaine could extend the duration of analgesia after major reconstructive penile surgery and also to measure the systemic absorption of morphine after caudal injection. Thirty children undergoing reconstructive penile surgery received a caudal injection of 0.25% bupivacaine 0.75 ml.kg-1 with or without morphine 0.05 mg.kg-1. All patients awoke pain-free, but eight of the fifteen patients receiving bupivacaine alone required supplementary injections of opioid postoperatively, whereas none of the patients receiving the bupivacaine-morphine mixture required additional opioids. The incidence of side-effects was similar for the two groups. Morphine was absorbed rapidly after caudal injection to reach a peak plasma level of 21.2 (+/- 4.8) ng.ml-1 at ten minutes and then fell to 10.1 (+/- 3.8) ng.ml-1 at one hour and 4.1 (+/- 2.6) ng.ml-1 at three hours. These levels are low compared with plasma levels associated with systemic analgesia. We conclude that the extended duration of analgesia from morphine 0.05 mg/kg given caudally is due at least in part to specific spinal analgesia. PMID:2012289

Wolf, A R; Hughes, D; Hobbs, A J; Prys-Roberts, C

1991-02-01

250

A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects  

PubMed Central

Background In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. Methods A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. Results The plasma DPP-4 activity–time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97–1.04) and 0.92 (0.82–1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration–time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80–1.25. Both the FDC and separate tablets were well tolerated. Conclusion The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach.

Park, Sang-In; Lee, Howard; Oh, Jaeseong; Lim, Kyoung Soo; Jang, In-Jin; Kim, Jeong-Ae; Jung, Jong Hyuk; Yu, Kyung-Sang

2015-01-01

251

Oral health Oral health  

E-print Network

Prams asks about the care of teeth during pregnancy: whether the mother had a dental problem, went to a dentist or dental clinic or discussed oral hygiene with a dentist or other healthcare worker. Public health importance A pregnant woman’s oral health affects the woman, her fetus and infant. In pregnant women, periodontal disease, which affects the gums and adjacent bone, is associated with pre-term and/or low birth-weight delivery. 1, 2, 3 After delivery, infants or young children may develop cavities from maternal oral bacteria. 4 All health care providers can promote oral health through oral examinations; advising patients about oral hygiene, diet and smoking cessation; and by making referrals to oral health practitioners. 5 Access to oral health services during pregnancy may be constrained by the American Dental Association recommendations to avoid elective dental care during the first trimester and last half of the third trimester. 6 In four PRAMS states, among mothers who reported having a dental problem, about one-half did not go for care. 7 NM PRAMS findings In 2002, 25 % of mothers recalled discussion of oral hygiene during prenatal care (Table 56 / Figure 28), 13% had a dental problem and 33 % had dental care (Table 57 / Figure 29). Among women with a dental problem, 56% had dental care (Table 58 / Figure 30). In 2001-2002, women who were more likely to have dental care included those with insurance, without public assistance or with more than high school education. Use of oral health

unknown authors

252

Endogenous formation of morphine in human cells Chotima Poeaknapo*, Ju rgen Schmidt  

E-print Network

origin because morphine has been reported to occur in hay, lettuce, human milk, and cow milk, as well morphine (and any intermediate in the biosynthetic process as well) in specific positions. In this study

Kharasch, Evan

253

E-Books and the Tablet PC.  

ERIC Educational Resources Information Center

Highlights the emerging technologies of e-books, electronic versions of texts, and the Tablet PC, a new hybrid laptop computer and personal digital assistant that features a writing tablet and stylus-based input/navigation. (Author/VWL)

Goodwin-Jones, Bob

2003-01-01

254

21 CFR 520.1310 - Marbofloxacin tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Marbofloxacin tablets. 520.1310 Section 520...FORM NEW ANIMAL DRUGS § 520.1310 Marbofloxacin tablets. (a) Specifications ...50, 100, or 200 milligrams (mg) marbofloxacin. (b) Sponsor. See No....

2010-04-01

255

21 CFR 520.1380 - Methocarbamol tablets.  

...DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy)-1,2-propanediol 1-carbamate. (b) Specifications. Each tablet contains 500 milligrams of methocarbamol. (c) Sponsor. See No. 000856...

2014-04-01

256

21 CFR 520.1380 - Methocarbamol tablets.  

Code of Federal Regulations, 2010 CFR

...DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy)-1,2-propanediol 1-carbamate. (b) Specifications. Each tablet contains 500 milligrams of methocarbamol. (c) Sponsor. See No. 000856...

2010-04-01

257

21 CFR 520.1380 - Methocarbamol tablets.  

Code of Federal Regulations, 2013 CFR

...DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy)-1,2-propanediol 1-carbamate. (b) Specifications. Each tablet contains 500 milligrams of methocarbamol. (c) Sponsor. See No. 000856...

2013-04-01

258

21 CFR 520.1380 - Methocarbamol tablets.  

Code of Federal Regulations, 2011 CFR

...DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy)-1,2-propanediol 1-carbamate. (b) Specifications. Each tablet contains 500 milligrams of methocarbamol. (c) Sponsor. See No. 000856...

2011-04-01

259

21 CFR 520.1380 - Methocarbamol tablets.  

Code of Federal Regulations, 2012 CFR

...DRUGS § 520.1380 Methocarbamol tablets. (a) Chemical name. 3-(O-Methoxyphenoxy)-1,2-propanediol 1-carbamate. (b) Specifications. Each tablet contains 500 milligrams of methocarbamol. (c) Sponsor. See No. 000856...

2012-04-01

260

21 CFR 520.312 - Carnidazole tablets.  

Code of Federal Regulations, 2010 CFR

...Conditions of use —(1) Amount. Adult pigeons: 1 tablet (10 milligrams); newly weaned pigeons: 1/2 tablet (5 milligrams). (2...trichomoniasis (canker) in ornamental and homing pigeons. (3) Limitations. Not for...

2010-04-01

261

21 CFR 520.312 - Carnidazole tablets.  

Code of Federal Regulations, 2011 CFR

...Conditions of use —(1) Amount. Adult pigeons: 1 tablet (10 milligrams); newly weaned pigeons: 1/2 tablet (5 milligrams). (2...trichomoniasis (canker) in ornamental and homing pigeons. (3) Limitations. Not for...

2011-04-01

262

21 CFR 520.2088 - Roxarsone tablets.  

Code of Federal Regulations, 2012 CFR

...Conditions of use —(i) Growing chickens and growing turkeys—(a ) Amount. Dissolve 2 tablets in each gallon of... (4) Conditions of use in growing chickens and growing turkeys —(i) Amount . 1 tablet in each gallon of drinking...

2012-04-01

263

21 CFR 520.2088 - Roxarsone tablets.  

Code of Federal Regulations, 2010 CFR

...Conditions of use —(i) Growing chickens and growing turkeys—(a ) Amount. Dissolve 2 tablets in each gallon of... (4) Conditions of use in growing chickens and growing turkeys —(i) Amount . 1 tablet in each gallon of drinking...

2010-04-01

264

21 CFR 520.2088 - Roxarsone tablets.  

Code of Federal Regulations, 2013 CFR

...Conditions of use —(i) Growing chickens and growing turkeys—(a ) Amount. Dissolve 2 tablets in each gallon of... (4) Conditions of use in growing chickens and growing turkeys —(i) Amount . 1 tablet in each gallon of drinking...

2013-04-01

265

21 CFR 520.2088 - Roxarsone tablets.  

Code of Federal Regulations, 2011 CFR

...Conditions of use —(i) Growing chickens and growing turkeys—(a ) Amount. Dissolve 2 tablets in each gallon of... (4) Conditions of use in growing chickens and growing turkeys —(i) Amount . 1 tablet in each gallon of drinking...

2011-04-01

266

Bioequivalence study of 400 and 100 mg imatinib film-coated tablets in healthy volunteers.  

PubMed

The aim of the study was to investigate the bioavailability of a generic product of 100 mg and 400 mg imatinib film-coated tablets (test) as compared to that of a branded product (reference) at the same strength to determine bioequivalence. The secondary objective of the study was to evaluate tolerability of both products. An open-label, randomized, crossover, two-period, single-dose, comparative study was conducted in 43 (Imatynib-Biofarm 100 mg film-coated tablet) and in 42 (Imatynib-Biofarm 400 mg film-coated tablet), brand name Imatenil, Caucasian healthy volunteers in fed conditions. A single oral dose administration of the test or reference product was separated by 14-day washout period. The imatinib and its metabolite N-desmethyl imatinib concentrations were determined using a validated LC MS/MS method. The results of the single-dose study in healthy volunteers indicated that the film-coated tablets of Imatynib-Biofarm 100 mg and 400 mg film-coated tablets manufactured by Biofarm Sp. z o.o. (test products) are bioequivalent to those of Glivec 100 mg and 400 mg film-coated tablets manufactured by Novartis Pharma GmbH (reference products). Both products in the two doses of imatinib were well tolerated. PMID:25362813

Ostrowicz, Andrzej; Miko?ajczak, Przemys?aw L; Wierzbicka, Marzena; Boguradzki, Piotr

2014-01-01

267

Quantitative analysis of visible surface defect risk in tablets during film coating using terahertz pulsed imaging.  

PubMed

Tablets are the most common form of solid oral dosage produced by pharmaceutical industries. There are several challenges to successful and consistent tablet manufacturing. One well-known quality issue is visible surface defects, which generally occur due to insufficient physical strength, causing breakage or abrasion during processing, packaging, or shipping. Techniques that allow quantitative evaluation of surface strength and the risk of surface defect would greatly aid in quality control. Here terahertz pulsed imaging (TPI) was employed to evaluate the surface properties of core tablets with visible surface defects of varying severity after film coating. Other analytical methods, such as tensile strength measurements, friability testing, and scanning electron microscopy (SEM), were used to validate TPI results. Tensile strength and friability provided no information on visible surface defect risk, whereas the TPI-derived unique parameter terahertz electric field peak strength (TEFPS) provided spatial distribution of surface density/roughness information on core tablets, which helped in estimating tablet abrasion risk prior to film coating and predicting the location of the defects. TPI also revealed the relationship between surface strength and blending condition and is a nondestructive, quantitative approach to aid formulation development and quality control that can reduce visible surface defect risk in tablets. PMID:24300215

Niwa, Masahiro; Hiraishi, Yasuhiro

2014-01-30

268

Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine  

Microsoft Academic Search

Introduction: There is considerable and unexplained individual variability in the morphine dose-effect relationship. The efflux pump P-glycoprotein regulates brain access and intestinal absorption of numerous drugs. Morphine is a P-glycoprotein substrate in vitro, and P-glycoprotein affects morphine brain access and pharmacodynamics in animals. However, the role of P-glycoprotein in human morphine disposition and clinical effects is unknown. This investigation tested

Evan D. Kharasch; Christine Hoffer; Dale Whittington; Pam Sheffels

2003-01-01

269

Extended-release morphine sulfate in treatment of severe acute and chronic pain  

PubMed Central

Morphine is the archetypal opioid analgesic. Because it is a short-acting opioid, its use has been limited to the management of acute pain. The development of extended-release formulations have resulted in the increased utilization of morphine in chronic pain conditions. This review documents the history of morphine use in pain treatment, and describes the metabolism, pharmacodynamics, formulations, and efficacy of the currently available extended-release morphine medications. PMID:21197323

Balch, Robert J; Trescot, Andrea

2010-01-01

270

Combining diclofenac with acetaminophen or acetaminophen-codeine after oral surgery: A randomized, double-blind single-dose study  

Microsoft Academic Search

In a randomized double-blind study, 120 patients with moderate to strong pain after surgical removal of wisdom teeth were given the following in single oral doses: 100-mg enteric-coated diclofenac tablets; 1 g acetaminophen (INN, paracetamol); 1 g acetaminophen plus 60 mg codeine; 100-mg enteric-coated diclofenac tablets plus 1 g acetaminophen; or 100-mg enteric-coated diclofenac tablets plus 1 g acetaminophen plus

Else Kristine Breivik; Pål Barkvoll; Eva Skovlund

1999-01-01

271

Novel gastroretentive sustained-release tablet of tacrolimus based on self-microemulsifying mixture: in vitro evaluation and in vivo bioavailability test  

PubMed Central

Aim: To develop a novel gastroretentive drug delivery system based on a self-microemulsifying (SME) lipid mixture for improving the oral absorption of the immunosuppressant tacrolimus. Methods: Liquid SME mixture, composed of Cremophor RH40 and monocaprylin glycerate, was blended with polyethylene oxide, chitosan, polyvinylpyrrolidone and mannitol, and then transformed into tablets via granulation, with ethanol as the wetting agent. The tablets were characterized in respect of swelling, bioadhesive and SME properties. In vitro dissolution was conducted using an HCl buffer at pH 1.2. Oral bioavailability of the tablets was examined in fasted beagle dogs. Results: The tablet could expand to 13.5 mm in diameter and 15 mm in thickness during the initial 20 min of contact with the HCl buffer at pH 1.2. The bioadhesive strength was as high as 0.98±0.06 N/cm2. The SME gastroretentive sustained-release tablets preserved the SME capability of the liquid SME formations under transmission electron microscope. The drug-release curve was fit to the zero-order release model, which was helpful in reducing fluctuations in blood concentration. Compared with the commercially available capsules of tacrolimus, the relative bioavailability of the SME gastroretentive sustained-release tablets was 553.4%±353.8%. Conclusion: SME gastroretentive sustained-release tablets can enhance the oral bioavailability of tacrolimus with poor solubility and a narrow absorption window. PMID:21927013

Wang, Yan-ping; Gan, Yong; Zhang, Xin-xin

2011-01-01

272

Identification of Morphine Accumulation in the Rat Embryo Central Nervous System: A C14-Morphine Administration Study  

PubMed Central

Background: Previous studies have shown that morphine consumption during pregnancy may cause delay or defect of embryo development or abnormal nervous system function in the human and animal models. In the present study, the highest density of morphine accumulation in the central nervous system of rat embryos was evaluated using C14-morphine. Methods: Female Wistar rats (W 170-200 g) used and were crossed with male rats and coupling time was recorded (Embryonic day 0-E0). Experimental groups received 0.05 mg/ml of C14-morphine in drinking water daily. On the 10th and 17th days of pregnancy, pregnant rats were anesthetized and the embryos with these uterus and placenta were surgically removed and were fixed in formalin 10% for 4 week. Then the embryos were processed, sectioned in 25 ?m and 5 ?m thicknesses, fixed on the glasses for further evaluations. The sectioned in 25, the glasses were fixed on the Blanc black and white film for 6 h. Then, the films were appeared and their negatives were prepared. The sectioned in five staining hematoxylin and eosin by light microscope and MOTIC software. Results: Our results indicated that the highest C14-morphine accumulation was observed in the vesicles and the ventricular choroid plexus (CP) of (E17) embryos, whereas, in the (E10) embryos. Highest concentration was observed in the brain vesicles and the ventricular CP. In addition, this study showed the surface area of lateral, 3rd and 4th ventricular CP in the experimental groups were increased in compared to control groups. Conclusions: Our results indicated that effects of morphine on reduction of embryos brain development may be due to the highest accumulation of C14-morphine in the CP and brain vesicles. PMID:23776728

Sahraei, Hedayat; Rostamkhani, Fatemeh; Tekieh, Elaheh; Dehghani, Leila; Poorazizi, Elahe; Meamar, Rokhsareh; Kazemi, Masoomeh

2013-01-01

273

21 CFR 520.816 - Epsiprantel tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Epsiprantel tablets. 520.816 Section 520.816 Food...ANIMAL DRUGS § 520.816 Epsiprantel tablets. (a) Specifications . Each tablet contains either 12.5, 25, 50, or 100 milligrams of...

2010-04-01

274

Scaffolding Equals Success in Teaching Tablet PCs  

ERIC Educational Resources Information Center

After many years of using the mouse and keyboard as the primary means of computer input, people are seeing a strong surge into a new generation of input technologies such as tablet PCs. As more professionals adopt tablet PCs for use in the workplace, there is a subsequent increased demand for tablet PC instruction in the classroom. Examples of…

Dickerson, Jeremy; Williams, Scott; Browning, J. B.

2009-01-01

275

Onsite Wastewater Treatment Systems: Tablet Chlorination  

E-print Network

the basin. As that tablet dissolves and/or erodes, the tablet above it falls by gravity to replace it. A tablet can dissolve quickly or slowly, depending on the amount of wastewater coming into contact Richard Weaver and Bruce Lesikar Professor in Soil...

Lesikar, Bruce J.

2008-10-23

276

Paradoxical Effects after Microinjection of Morphine in the Periaqueductal Gray Matter in the Rat  

Microsoft Academic Search

Paradoxical, concurrent hyper- and hyporeactivity of a profound nature to specific stimuli occurred when 10 micrograms of morphine was microinjected bilaterally into the periaqueductal gray matter of the rat brain. Both effects at this site were dose-dependent. The hyperreactivity (to previously neutral auditory and visual stimuli) was obtained only with intracerebrally injected morphine and never with intraperitoneally injected morphine or

Yasuko F. Jacquet; Abel Lajtha

1974-01-01

277

BIOTRANSFORMATIONS OF MORPHINE ALKALOIDS BY FUNGI: N-DEMETHYLATIONS, OXIDATIONS, AND REDUCTIONS  

E-print Network

BIOTRANSFORMATIONS OF MORPHINE ALKALOIDS BY FUNGI: N-DEMETHYLATIONS, OXIDATIONS, AND REDUCTIONS on the occasion of his 85th birthday. Morphine alkaloids and some of its derivatives (morphine, codeine, thebaine. The alkaloids were transformed to a variety of products via biological oxidations, reductions, and oxidative

Hudlicky, Tomas

278

Ondansetron for treatment of intrathecal morphine-induced pruritus after cesarean delivery  

Microsoft Academic Search

Background and Objectives: Pruritus induced by intrathecal morphine is a concern in many obstetric patients after cesarean delivery and may detract from the benefit of postoperative pain relief. This study was performed to investigate the efficacy of ondansetron (5-HT3 receptor antagonist) in treatment of pruritus following intrathecal morphine. Methods: Eighty parturients developing moderate to severe pruritus following intrathecal morphine were

S. Charuluxananan; W. Somboonviboon; O. Kyokong; K. Nimcharoendee

2000-01-01

279

Morphine and Heroin Differentially Modulate In Vivo Hippocampal LTP in Opiate-Dependent Rat  

E-print Network

Morphine and Heroin Differentially Modulate In Vivo Hippocampal LTP in Opiate-Dependent Rat Guobin in heroin-dependent rats, but heroin could not restore the reduced LTP, in morphine-dependent rats-exposure of morphine but not that of heroin, suggesting a likely underlying mechanism of the differential modulation

Tian, Weidong

280

Metronidazole Oral  

MedlinePLUS

Metronidazole eliminates bacteria and other microorganisms that cause infections of the reproductive system, gastrointestinal tract, skin, vagina, ... Metronidazole comes as a tablet to take by mouth. It is usually taken two or three times ...

281

Effect of morphine on sympathetic nerve activity in humans  

NASA Technical Reports Server (NTRS)

There are conflicting reports for the role of endogenous opioids on sympathetic and cardiovascular responses to exercise in humans. A number of studies have utilized naloxone (an opioid-receptor antagonist) to investigate the effect of opioids during exercise. In the present study, we examined the effect of morphine (an opioid-receptor agonist) on sympathetic and cardiovascular responses at rest and during isometric handgrip (IHG). Eleven subjects performed 2 min of IHG (30% maximum) followed by 2 min of postexercise muscle ischemia (PEMI) before and after systemic infusion of morphine (0.075 mg/kg loading dose + 1 mg/h maintenance) or placebo (saline) in double-blinded experiments on separate days. Morphine increased resting muscle sympathetic nerve activity (MSNA; 17 +/- 2 to 22 +/- 2 bursts/min; P < 0.01) and increased mean arterial pressure (MAP; 87 +/- 2 to 91 +/- 2 mmHg; P < 0.02), but it decreased heart rate (HR; 61 +/- 4 to 59 +/- 3; P < 0.01). However, IHG elicited similar increases for MSNA, MAP, and HR between the control and morphine trial (drug x exercise interaction = not significant). Moreover, responses to PEMI were not different. Placebo had no effect on resting, IHG, and PEMI responses. We conclude that morphine modulates cardiovascular and sympathetic responses at rest but not during isometric exercise.

Carter, Jason R.; Sauder, Charity L.; Ray, Chester A.

2002-01-01

282

Evaluation of some compression aids in tableting of roller compacted swellable core drug layer.  

PubMed

Swellable core technology (SCT) represents a broadly applicable oral osmotic drug delivery platform for the controlled release of drugs. SCT tablets control drug delivery by using osmosis to regulate the influx of water into the tablet's core. The tablet consists of two layers; drug layer and sweller layer, with a semi-permeable membrane coating and delivery port located in the drug layer side of the tablet. The key component of SCT formulations is polyethylene oxide (PEO), which is typically wet granulated with organic solvents to prevent rapid gel hydration observed during contact with aqueous environments. However, the use of organic solvents has their own environmental and cost considerations which make this form of processing undesirable. To overcome this issue, dry granulation can be employed. However, PEO is a very plastic material and problems may be encountered during the tableting process, when work hardening occurs upon double compression. The addition of compression aids to the drug layer will help to increase the roll force when generating ribbons - reducing fines and segregation potential - while also reducing work hardening effects which impact tablet friability. The five compression aids used in this study were microcrystalline cellulose (MCC), xylitol, di-calcium phosphate (anhydrous), lactose monohydrate and starch. The work undertaken here studies the compression properties of the drug layer blends with different levels of the five compression aids as part of the formulation. Roller compaction properties are also varied to provide granules with differing solid fractions. The results of this study indicate that addition of microcrystalline cellulose in the formulation in levels between 10% and 30% significantly improve the tablet hardness at lower tablet compression forces. Further work is required to investigate the impact on dissolution. PMID:23796839

Golchert, D; Bines, E; Carmody, A

2013-09-10

283

?-Opioid receptor desensitization: Is morphine different?  

PubMed Central

Opioid tolerance and dependence are important phenomena. The contribution of acute ?-opioid receptor regulatory mechanisms to the development of analgesic tolerance or physical dependence are unknown, and even the mechanisms underlying relatively rapid receptor desensitization in single cells are unresolved. To a large degree, the uncertainty surrounding the mechanisms and consequences of short-term regulation of ?-opioid receptors in single cells arises from the limitations in the experimental design in many of the studies that have investigated these events. Receptor overexpression and use of assays in which regulatory mechanisms are likely to blunt control determinations have led to measurements of opioid receptor activity that are likely to be insensitive to receptor uncoupling. Together with uncertainties concerning molecular details of ?-opioid receptor interactions with potential regulatory molecules such as G protein-coupled receptor kinases and arrestins, we are left with an incomplete picture crudely copied from the well-worked-out regulatory schema for ?2-adrenoceptors. As a consequence, suggestions that clinically relevant ?-opioid receptor agonists may have different propensities to produce tolerance and dependence that arise from their differential recruitment of regulatory mechanisms are premature, and have not yet been appropriately assessed, nor explained in the context of a thoroughly established regulatory scheme. In this commentary, we outline the experimental limitations that have given rise to conflicting ideas about how ?-opioid receptors are regulated, and identify the issues we feel still need to be addressed before we can understand why morphine promotes receptor trafficking differently to other opioids. PMID:15504746

Connor, Mark; Osborne, Peregrine B; Christie, MacDonald J

2004-01-01

284

Comprehensive review on oral disintegrating films.  

PubMed

Fast-dissolving drug-delivery systems were first developed in the late 1970s as an alternative to tablets, capsules, and syrups for pediatric and geriatric patients who experience difficulties swallowing traditional oral solid dosage forms. In response to this need, a variety of orally disintegrating tablet (ODT) formats were commercialized, which disintegrate within 1 min when placed in the mouth without drinking water or chewing. Oral drug delivery technology has improved from conventional dosage forms to modified release dosage forms to ODT to the recent oral disintegrating films (ODF). Oral disintegrating film or strip that employs a water dissolving polymer which allows the dosage form to quickly hydrate by saliva, adhere to mucosa, and disintegrate within a few seconds, dissolve and releases medication for oromucosal absorption when placed on the tongue or oral cavity. Oral strip technology provides an alternate route for drugs with first pass metabolism. This review give details of materials used in ODF, manufacturing aspects, technologies, evaluation tests and marketed products. PMID:22920576

Nagaraju, T; Gowthami, R; Rajashekar, M; Sandeep, S; Mallesham, M; Sathish, D; Kumar, Y Shravan

2013-02-01

285

[Effectiveness of switching opioids from fentanyl patch to morphine injection].  

PubMed

Patients endure the switching of opioids from fentanyl patch to morphine injection to improve inadequate pain relief. We retrospectively examined the differences between the maintenance dose of morphine injection after switching, its estimated dose prior to switching, and some other factors. As a result, 8 out of 9 patients had pain control after switching. Also, patients who increased the dose of the fentanyl patch more than twice in a month before switching required a significantly lower maintenance dose for the estimated dose after switching (p < 0.05) than those who took less. In conclusion, switching opioids to morphine injection is very effective, both from the viewpoint of pain control and the reduction of the amount of opioids used for patients with poor pain control, who frequently increase their use of the fentanyl patch. PMID:23848029

Sako, Azumi; Kikuchi, Norihiro; Wada, Yoshichika; Wakabayashi, Satoshi

2013-04-01

286

Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity  

SciTech Connect

The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.

Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

1984-04-01

287

Preparation and evaluation of sublingual tablets of zolmitriptan  

PubMed Central

Aim: Zolmitriptan is a 5-HT receptor agonist (1B/1D). It is used in the acute treatment of migraine having low bioavailability about 40% orally due to hepatic first pass metabolism. The purpose of the present research was to formulate fast acting sublingual tablets of zolmitriptan. Materials and Methods: Sublingual tablets were prepared using ispaghula husk powder, gellan gum, sodium alginate as super disintegrating polymers and citric acid, tartaric acid and camphor as permeation enhancers by direct compressible technique and evaluated for weight variation, thickness, friability, content uniformity, hardness, disintegration time, wetting time, in-vitro drug release, in-vitro and ex-vivo permeation study. Stability study of optimized formulation was performed as per ICH (International Conference on Harmonisation) guideline. Results: The in-vitro disintegration time of the optimized formulation (D5) was 9 ± 2 s and all formulations showed 100% of dissolution within 6 ± 2 min. Formulation containing 4% of gellan gum (D5) showed highest disintegration and 2% of citric acid formulation (P3) showed highest permeation 88% within 30 min and ex-vivo permeation was 52% within 30 min. Optimized formulation was stable for 1 month during stability study as per ICH guideline. Conclusion: The sublingual tablet formulation gives better results using natural super disintegrant for fast onset of action. PMID:24678459

Prajapati, Shailesh T; Patel, Manoj V; Patel, Chhaganbhai N

2014-01-01

288

Prolonged morphine treatment alters ? opioid receptor post-internalization trafficking  

PubMed Central

BACKGROUND AND PURPOSE The ? opioid receptor (DOP receptor) undergoes internalization both constitutively and in response to agonists. Previous work has shown that DOP receptors traffic from intracellular compartments to neuronal cell membranes following prolonged morphine treatment. Here, we examined the effects of prolonged morphine treatment on the post-internalization trafficking of DOP receptors. EXPERIMENTAL APPROACH Using primary cultures of dorsal root ganglia neurons, we measured the co-localization of endogenous DOP receptors with post-endocytic compartments following both prolonged and acute agonist treatments. KEY RESULTS A departure from the constitutive trafficking pathway was observed following acute DOP receptor agonist-induced internalization by deltorphin II. That is, the DOP receptor underwent distinct agonist-induced post-endocytic sorting. Following prolonged morphine treatment, constitutive DOP receptor trafficking was augmented. SNC80 following prolonged morphine treatment also caused non-constitutive DOP receptor agonist-induced post-endocytic sorting. The ? opioid receptor (MOP receptor) agonist DAMGO induced DOP receptor internalization and trafficking following prolonged morphine treatment. Finally, all of the alterations to DOP receptor trafficking induced by both DOP and MOP receptor agonists were inhibited or absent when those agonists were co-administered with a DOP receptor antagonist, SDM-25N. CONCLUSIONS AND IMPLICATIONS The results support the hypothesis that prolonged morphine treatment induces the formation of MOP–DOP receptor interactions and subsequent augmentation of the available cell surface DOP receptors, at least some of which are in the form of a MOP/DOP receptor species. The pharmacology and trafficking of this species appear to be unique compared to those of its individual constituents. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24819092

Ong, E W; Xue, L; Olmstead, M C; Cahill, C M

2015-01-01

289

Effect of cinitapride in isolated ileum obtained from guinea-pigs treated with morphine.  

PubMed

1. Cinitapride enhanced the contractile response induced by electrical stimulation in the guinea-pig myenteric plexus-longitudinal muscle strip preparations. 2. The contractile force was significantly increased in strips pretreated with morphine "in vitro" and in tolerant strips. 3. However when tissues were obtained from tolerant guinea-pigs and morphine was not added to the organ bath (morphine-abstinence), the cinitapride effect was significantly decreased. 4. Although further work is required to explain the changes in the effect of cinitapride after acute morphine treatment and in morphine tolerant tissues, the changes observed suggest that some of the cinitapride effects could be linked with the peripheral opioid system. PMID:1662171

Colado, M I; Alfaro, M J; del Val, V L; Martín, M I

1991-01-01

290

In situ, real time observation of the disintegration of paracetamol tablets in aqueous solution by magnetic resonance imaging.  

PubMed

The disintegration behavior of paracetamol tablets was studied by magnetic resonance imaging (MRI) using the Snapshot FLASH method. The total time of the single experiment is 425 ms and allows the study of the disintegration process in real time. The study was carried out in vitro under acidic gastric pH conditions and may help to predict the behavior of paracetamol tablets in the stomach after oral administration. It was shown that in spite of identical conditions, the disintegration of the tablets under study was different. The distribution of protons of 4-(N-acetyl)aminophenol within the paracetamol tablet was shown to be homogeneous. The study was carried out in a non-destructive way by the SPI MRI method. PMID:11988395

Tritt-Goc, Jadwiga; Kowalczuk, Joanna

2002-05-01

291

Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects  

PubMed Central

Background Efforts to ease administration and enhance acceptability of the oral anti-malarial artemether-lumefantrine (A-L) crushed tablet to infants and children triggered the development of a novel dispersible tablet of A-L. During early development of this new formulation, two studies were performed in healthy subjects, one to evaluate the palatability of three flavours of A-L, and a second one to compare the bioavailability of active principles between the dispersible tablet and the tablet (administered crushed and intact). Methods Study 1 was performed in 48 healthy schoolchildren in Tanzania. Within 1 day, all subjects tasted a strawberry-, orange- and cherry-flavoured oral A-L suspension for 10 seconds (without swallowing) in a randomized, single-blind, crossover fashion. The palatability of each formulation was rated using a visual analogue scale (VAS). Study 2 was an open, randomized crossover trial in 48 healthy adults given single doses of A-L (80 mg artemether + 480 mg lumefantrine) with food. The objectives were to compare the bioavailability of artemether, dihydroartemisinin (DHA) and lumefantrine between the dispersible tablet and the tablet administered crushed (primary objective) and intact (secondary objective). Results Study 1 showed no statistically significant difference in VAS scores between the three flavours but cherry had the highest score in several ratings (particularly for overall liking). Study 2 demonstrated that the dispersible and crushed tablets delivered bioequivalent artemether, DHA and lumefantrine systemic exposure (area under the curve [AUC]); mean ± SD AUC0-tlast were 208 ± 113 vs 195 ± 93 h.ng/ml for artemether, 206 ± 81 vs 199 ± 84 h.ng/ml for DHA and 262 ± 107 vs 291 ± 106 h.?g/ml for lumefantrine. Bioequivalence was also shown for peak plasma concentrations (Cmax) of DHA and lumefantrine. Compared with the intact tablet, the dispersible tablet resulted in bioequivalent lumefantrine exposure, but AUC and Cmax values of artemether and DHA were 20-35% lower. Conclusions Considering that cherry was the preferred flavour, and that the novel A-L dispersible tablet demonstrated similar pharmacokinetic performances to the tablet administered crushed, a cherry-flavoured A-L dispersible tablet formulation was selected for further development and testing in a large efficacy and safety study in African children with malaria. PMID:20815879

2010-01-01

292

Increased Clearance of Morphine in Sickle Cell Disease: Implications for Pain Management  

PubMed Central

Acute vaso-occlusive painful episodes associated with sickle cell disease (SCD) are frequently treated with morphine. Many SCD individuals require relatively higher doses of morphine to achieve optimal analgesia. We studied pharmacokinetics of morphine in SCD to explore if altered disposition could be a factor for increased requirement of morphine in this population. The study subjects were in steady state of health to avoid the effect of hemodynamic changes associated with vaso-occlusion on morphine disposition. The plasma concentrations of morphine and its major metabolites were measured at timed intervals in 21 SCD subjects after they received a single 0.1 mg/ Kg infusion of morphine sulfate. USCPACK software was used to fit candidate pharmacokinetic models. Non-compartmental pharmacokinetic parameters for morphine were calculated. Morphine clearance was 2.4 – 3.6 L/h, half-life was 0.3 – 0.7 hours, AUC0?? was 27.7 – 42.5 ng*h/mL, and volume of distribution was 0.96 – 3.38 L/kg. Clearance of morphine in the study population was 3 – 10 folds higher than published estimates in the non-SCD population, with correspondingly lower AUC and half-life. Volume of distribution was similar. This observation suggests that due to increased clearance SCD individuals may require higher dose and frequency of morphine to achieve comparable plasma levels. PMID:21277838

Darbari, Deepika S.; Neely, Michael; van den Anker, John; Rana, Sohail

2010-01-01

293

The effects of morphine on basal neuronal activities in the lateral and medial pain pathways  

PubMed Central

Numerous studies indicate that morphine suppresses pain-evoked activities in both spinal and supraspinal regions. However, little is known about the effect of morphine on the basal brain activity in the absence of pain. The present study was designed to assess the effects of single-dose morphine on the spontaneous discharge of many simultaneously recorded single units, as well as their functional connections, in the lateral pain pathway, including the primary somatosensory cortex (SI) and ventral posterolateral thalamus (VPL), and medial pain pathway, including the anterior cingulate cortex (ACC) and medial dorsal thalamus (MD), in awake rats. Morphine (5mg/kg) was administered intraperitoneally before the recording. Naloxone plus morphine and normal saline injections were performed respectively as controls. The results showed that morphine administration produced significant changes in the spontaneous neuronal activity in more than one third of the total recorded neurons, with primary activation in the lateral pathway while both inhibition and activation in the medial pathway. Naloxone pretreatment completely blocked the effects induced by morphine. In addition, the correlated activities between and within both pain pathways was exclusively suppressed after morphine injection. These results suggest that morphine may play different roles in modulating neural activity in normal versus pain states. Taken together, this is the first study investigating the morphine modulation of spontaneous neuronal activity within parallel pain pathways. It can be helpful for revealing neuronal population coding for the morphine action in the absence of pain, and shed light on the supraspinal mechanisms for preemptive analgesia. PMID:22841696

Su, Yuan-Lin; Huang, Jin; Wang, Ning; Wang, Jin-Yan; Luo, Fei

2012-01-01

294

Crystallization of excipients in tablets.  

PubMed

Whisker-like crystals appeared on the surface of tablets that contained lactose or mannitol, a hygroscopic material such as docusate sodium, magnesium chloride, or potassium acetate, and other ingredients stored in an atmosphere of high relative humidity. The crystals were observed under a scanning electron microscope and were measured using differential scanning calorimetry and TLC. The crystals contained lactose or mannitol. PMID:3921688

Ando, H; Watanabe, S; Ohwaki, T; Miyake, Y

1985-02-01

295

Morphine with adjuvant ketamine versus higher dose of morphine alone for acute pain: a meta-analysis  

PubMed Central

Purpose: Ketamine is currently the N-methyl-D-aspartate receptor channel blocker in clinical use. Morphine in pain management is usually limited by adverse effect such as nausea and vomiting. Adjuvant treatment with ketamine may be value in giving better analgesia with fewer adverse effects. The purpose of this meta-analysis was to evaluate the differences when patients received morphine with adjuvant ketamine (MK) compared with higher dose of morphine (MO) for acute pain. Methods: The PubMed, EMBASE and the Cochrane Library databases were searched (Last search performed on July 1, 2014) by two reviewers independently. Data were extracted independently by the same two individuals who searched the studies. Results: A total of 7 trials involving 492 patients were included in the current analysis. We found pain scores were lower in the MK group compared to the MO group [MD 2.19, 95% CI (1.24, 3.13) P<0.00001]. And more patients in the MO required diclofenac [OR 1.97, 95% CI (1.06, 3.67) P=0.03]. Furthermore, morphine plus ketamine can reduced post-operative nausea and vomiting (PONV) [OR 3.71, 95% CI (2.37, 5.80) P<0.00001]. Importantly, the wakefulness scores for the MK group were consistently and significantly better than those for the MO group [MD -1.53, 95% CI (-2.67, -0.40) P=0.008]. Conclusion: The use of ketamine plus 1/4~2/3 the dose of morphine is better than higher dose of morphine alone in reducing pain scores, and rescuing analgesic requirement. It also improved PONV and wakefulness. PMID:25356103

Ding, Xibing; Jin, Shuqing; Niu, Xiaoyin; Wang, Tingting; Zhao, Xiang; Ren, Hao; Tong, Yao; Li, Quan

2014-01-01

296

Effects of voluntary exercise on anxiety-like behavior and voluntary morphine consumption in rat pups borne from morphine-dependent mothers during pregnancy.  

PubMed

Exposure to morphine during pregnancy produced long-term effects in offspring behaviors. Recent studies have shown that voluntary exercise decreases the severity of anxiety behaviors in both morphine-dependent and withdrawn rats. Thus, the aims of the present study were to examine whether maternal exercise decreases prenatal dependence-induced anxiety and also, voluntary consumption of morphine in animal models of craving in rat pups. Pregnant rats were made dependent by chronic administration of morphine in drinking water simultaneously with access to a running wheel that lasted at least 21 days. Then, anxiety-like behaviors using the elevated plus-maze (EPM) and voluntary consumption of morphine using a two-bottle choice paradigm (TBC) were tested in male rat pups. The results showed that the rat pups borne from exercising morphine-dependent mothers exhibited an increase in EPM open arm time (P<0.0001) and entries (P<0.05) as compared with the sedentary groups. In animal models of craving showed that voluntary consumption of morphine in the rat pups borne from exercising morphine-dependent mothers was less in the second (P<0.032) and third (P<0.014) periods of intake as compared with the sedentary group. This study showed that maternal exercise decreases the severity of the anxiogenic-like behaviors and voluntary consumption of morphine in rat pups. PMID:24973610

Haydari, Sakineh; Miladi-Gorji, Hossein; Mokhtari, Amin; Safari, Manouchehr

2014-08-22

297

Magnetic images of the disintegration process of tablets in the human stomach by ac biosusceptometry  

NASA Astrophysics Data System (ADS)

Oral administration of solid dosage forms is usually preferred in drug therapy. Conventional imaging methods are essential tools to investigate the in vivo performance of these formulations. The non-invasive technique of ac biosusceptometry has been introduced as an alternative in studies focusing on gastrointestinal motility and, more recently, to evaluate the behaviour of magnetic tablets in vivo. The aim of this work was to employ a multisensor ac biosusceptometer system to obtain magnetic images of disintegration of tablets in vitro and in the human stomach. The results showed that the transition between the magnetic marker and the magnetic tracer characterized the onset of disintegration (t50) and occurred in a short time interval (1.1 ± 0.4 min). The multisensor ac biosusceptometer was reliable to monitor and analyse the in vivo performance of magnetic tablets showing accuracy to quantify disintegration through the magnetic images and to characterize the profile of this process.

Corá, L. A.; Andreis, U.; Romeiro, F. G.; Américo, M. F.; Oliveira, R. B.; Baffa, O.; Miranda, J. R. A.

2005-12-01

298

Technology of dispensing check based-on tablet features  

Microsoft Academic Search

This paper designs and realizes a bagged tablets checking system. First, according to tablet characteristics, color feature library and shape feature library are created. Second, the tablet image is clustered by K-means algorithm. And threshold segmentation for the tablet image use Ostu method. Finally, the recognition result of sorts of tablets in bag will compare with prescription in database written

Dong Yin; Jun Xu; Song Wang

2011-01-01

299

Novel gastroretentive sustained-release tablet of tacrolimus based on self-microemulsifying mixture: in vitro evaluation and in vivo bioavailability test  

Microsoft Academic Search

Aim:To develop a novel gastroretentive drug delivery system based on a self-microemulsifying (SME) lipid mixture for improving the oral absorption of the immunosuppressant tacrolimus.Methods:Liquid SME mixture, composed of Cremophor RH40 and monocaprylin glycerate, was blended with polyethylene oxide, chitosan, polyvinylpyrrolidone and mannitol, and then transformed into tablets via granulation, with ethanol as the wetting agent. The tablets were characterized in

Yan-ping Wang; Yong Gan; Xin-xin Zhang

2011-01-01

300

Pharmaceutical and analytical evaluation of triphalaguggulkalpa tablets  

PubMed Central

Aim of the Study: Development of standardized, synergistic, safe and effective traditional herbal formulations with robust scientific evidence can offer faster and more economical alternatives for the treatment of disease. The main objective was to develop a method of preparation of guggulkalpa tablets so that the tablets meet the criteria of efficacy, stability, and safety. Materials and Methods: Triphalaguggulkalpa tablet, described in sharangdharsanhita and containing guggul and triphala powder, was used as a model drug. Preliminary experiments on marketed triphalaguggulkalpa tablets exhibited delayed in vitro disintegration that indicated probable delayed in vivo disintegration. The study involved preparation of triphalaguggulkalpa tablets by Ayurvedic text methods and by wet granulation, dry granulation, and direct compression method. The tablets were evaluated for loss on drying, volatile oil content, % solubility, and steroidal content. The tablets were evaluated for performance tests like weight variation, disintegration, and hardness. Results: It was observed that triphalaguggulkalpa tablets, prepared by direct compression method, complied with the hardness and disintegration tests, whereas tablets prepared by Ayurvedic text methods failed. Conclusion: Direct compression is the best method of preparing triphalaguggulkalpa tablets. PMID:21731383

Savarikar, Shreeram S.; Barbhind, Maneesha M.; Halde, Umakant K.; Kulkarni, Alpana P.

2011-01-01

301

Intrathecal Morphine for Coronary Artery Bypass Grafting and Early Extubation  

Microsoft Academic Search

Aggressive control of pain during the immediate post- operative period after cardiac surgery with early tra- cheal extubation may decrease morbidity and mortal- ity. This prospective, randomized, double-blinded, placebo-controlled clinical study examined the use of intrathecal morphine in patients undergoing cardiac surgery and its influence on early tracheal extubation and postoperative analgesic requirements. Patients were randomized to receive either 10

Mark A. Chaney; Patricia A. Furry; Elaine M. Fluder; Stephen Slogoff

1997-01-01

302

Morphine-augmented cholescintigraphy in the diagnosis of acute cholecystitis  

SciTech Connect

Cholescintigraphy is a sensitive procedure for diagnosing or excluding acute cholecystitis. However, when rapid diagnosis is critical, the requirement for delayed images (4 hr or more after injection) to minimize the false-positive rate diminishes its utility. We prospectively evaluated 40 cholescintigraphic examinations that did not visualize the gallbladder 1 hr after injection of 99mTc diisopropyliminodiacetic acid. These examinations were then augmented by administration of IV morphine, followed by an additional 30 min of imaging. After the morphine, 18 of these examinations demonstrated visualization of the gallbladder; none subsequently required surgical exploration. Of the remaining 22, who demonstrated persistent nonvisualization of the gallbladder post-morphine, 11 were explored surgically and found to be abnormal. The 11 others were treated medically. Low-dose morphine administered when the gallbladder fails to visualize after 1 hr is a useful adjunct to conventional cholescintigraphy because it reduces the time required to obtain a diagnostic result and decreases the number of false-positive results.

Kim, E.E.; Pjura, G.; Lowry, P.; Nguyen, M.; Pollack, M.

1986-12-01

303

Use of morphine in cholescintigraphy for obstructive cholecystitis  

SciTech Connect

Non-visualization of the gallbladder (GB) during the first hour of cholescintigraphy is observed in cystic duct obstruction (e.g. in acute cholecystitis) but may also occur in chronic cholecystitis, hepatocellular disease, alcoholism and prolonged total parenteral nutrition. Low dose morphine is shown to improve the specificity of the diagnosis of acute cholecystitis (from 85% to 100%) with no loss in sensitivity (98%) at a small cost in terms of additional study time. The authors reviewed 27 selected cholescintigraphic examinations augmented by intravenous (IV) morphine (0.04 mg/Kg). Of the 16 cases with persistent nonvisualization of the GB, ultrasound revealed gallstones in 5 cases, sludge in 4, acalculous cholecystitis in 3, one distended GB, one contracted GB and 2 normal GB's. Of the 4 patients taken to surgery, one with gallstones and one with acalculous cholecystitis were confirmed to have acute cholecystitis while another with gallstones had chronic cholecystitis and the final patient, who was sonographically normal, presented a single common duct stone. The authors conclude that the use of IV morphine is an effective adjunct to cholescintigraphy in the evaluation of gallbladder disease, especially when visualization post morphine rules out acute cholecystitis.

Kim, E.E.; Nguyen, M.; Pjura, G.; Pollack, M.; Gobuty, A.

1985-05-01

304

Electroacupuncture Treatment Normalized Sleep Disturbance in Morphine Withdrawal Rats  

Microsoft Academic Search

Sleep disturbance is considered as an important symptom of acute and protracted opiate with- drawal. Current results suggest that sleep disturbance may be taken as a predictor of relapse. Appropriate sleep enhancement therapy will be in favor of the retention in treatment for opiate addicts. Our previous studies have shown that electroacupuncture (EA) is effective in suppres- sing morphine withdrawal

Yi-Jing Li; Fei Zhong; Peng Yu; Ji-Sheng Han; Cai-Lian Cui; Liu-Zhen Wu

305

Morphine-Dependent Rats: Blockade of Precipitated Abstinence by Tetrahydrocannabinol  

Microsoft Academic Search

Male rats were implanted subcutaneously with a pellet containing 75 milligrams of morphine base or placebo, and naloxone hydrochloride (4 milligrams per kilogram of body weight) was administered 72 hours later. Treatment with Delta 9-tetrahydrocannabinol (2, 5, or 10 milligrams per kilogram) 1 hour before naloxone administration significantly reduced the intensity of abstinence; the two higher doses blocked the appearance

B. Hine; E. Friedman; M. Torrelio; S. Gershon

1975-01-01

306

Site and mechanism of morphine tolerance in the gastrointestinal tract.  

PubMed

Opioid-induced constipation is a major clinical problem. The effects of morphine, and other narcotics, on the gastrointestinal tract persist over long-term use thus limiting the clinical benefit of these excellent pain relievers. The effects of opioids in the gut, including morphine, are largely mediated by the ?-opioid receptors at the soma and nerve terminals of enteric neurons. Recent studies demonstrate that regional differences exist in both acute and chronic morphine along the gastrointestinal tract. While tolerance develops to the analgesic effects and upper gastrointestinal motility upon repeated morphine administration, tolerance does not develop in the colon with chronic opioids resulting in persistent constipation. Here, we review the mechanisms by which tolerance develops in the small but not the large intestine. The regional differences lie in the signaling and regulation of the ?-opioid receptor in the various segments of the gastrointestinal tract. The differential role of ?-arrestin2 in tolerance development between central and enteric neurons defines the potential for therapeutic approaches in developing ligands with analgesic properties and minimal constipating effects. PMID:25257923

Akbarali, H I; Inkisar, A; Dewey, W L

2014-10-01

307

75 FR 11549 - Determination That PRO-BANTHINE (Propantheline Bromide) Tablets and 14 Other Drug Products Were...  

Federal Register 2010, 2011, 2012, 2013

...Moore Dr., P.O. Box Equivalent to (EQ) 300 13398, Research mg base/5 mL Triangle...HCl) Eli Lilly and Co., Oral Solution, EQ 20 Lilly Corporate mg base/5 mL Center...ibandronate Hoffmann LaRoche, sodium) Tablet, EQ 2.5 Inc., 340 Kingsland mg base...

2010-03-11

308

Evaluation of monolithic osmotic tablet system for nifedipine delivery in vitro and in vivo.  

PubMed

The aim of this study was to evaluate the monolithic osmotic tablet system (MOTS) containing a solid dispersion with the practically water-insoluble drug nifedipine in vitro and in vivo. In the drug release study in vitro, the release profiles of this system had almost zero-order kinetics. The influences of tablet formulation variables, sizes of the delivery orifice, membrane variables, and values of pH in the dissolution medium on nifedipine release from MOTS have been investigated. The results provided evidence that the tablet core played an important role in MOTS. While orifice sizes and membrane variables affected the nifedipine release rate, MOTS was independent of the dissolution medium. The appropriate orifice size was found to be in the range of 0.5-1.0 mm. The coating membrane incorporating hydrophilic polyethylene glycol (PEG) formed a porous structure. The human pharmacokinetics and relative bioavailability of MOTS containing nifedipine were compared with a commercial Adalat osmotic tablet system containing an equivalent dose of nifedipine following an oral single dose of 30 mg given to each of 11 healthy volunteers in an open, randomized crossover study in vivo. The relative bioavailability for MOTS was 112%. There was no statistically significant difference in the pharmacokinetic parameters between two dosage forms. It is concluded that the monolithic osmotic tablet controlled release system is feasible for a long-acting preparation as a once-daily treatment. PMID:12906339

Liu, Xing; Chen, Dawei; Zhang, Ruhua

2003-08-01

309

Development and evaluation of gastroretentive floating tablets of an antihypertensive drug using hydrogenated cottonseed oil.  

PubMed

The aim of the present work was to develop a gastroretentive floating tablet of Atenolol and investigate the effects of both hydrophilic and hydrophobic retardant on in vitro release. Atenolol is an antihypertensive drug with an oral bioavailability of only 50% because of its poor absorption from lower gastrointestinal tract. The floating tablets of Atenolol were prepared to increase the gastric retention, to extend the drug release, and to improve the bioavailability of the drug. The floating tablets were formulated using hydrophilic polymers as Hydroxy propyl methyl cellulose (HPMC K4M and HPMC K15M), hydrophobic retardant as a hydrogenated cottonseed oil (HCSO), and sodium bicarbonate as a gas generating agent to reduce floating lag time. The formulated tablets were evaluated for the quality control tests such as weight variation, hardness, friability, swelling index, floating lag time, and total floating time. The in vitro release study of the tablets was performed in 0.1?N HCl as a dissolution media. The results of the present study clearly indicates the promising potential of Atenolol floating system as an alternative to the conventional dosage and other sustained release formulations. The study also revealed the effectiveness of HCSO as retardant in combination with HPMC. PMID:24455312

Pawar, Harshal Ashok; Gharat, Pooja Ramchandra; Dhavale, Rachana Vivek; Joshi, Pooja Rasiklal; Rakshit, Pushpita Pankajkumar

2013-12-18

310

Increase in Plasma Concentrations of Geranylgeranoic Acid after Turmeric Tablet Intake by Healthy Volunteers  

PubMed Central

Geranylgeranoic acid (GGA) is one of the most potent cancer-preventive acyclic retinoids. GGA has been shown to induce cell death in human hepatoma-derived HuH-7 cells. We have recently reported the natural occurrence of GGA and its related compounds in several medicinal herbs such as turmeric, basil, rosehip, cinnamon and others [Shidoji and Ogawa, J. Lipid Res., 45: 1092–1103, 2004]. In the present study, we performed oral administration of turmeric tablets to healthy volunteers in order to investigate bioavailability of natural GGA. By using liquid chromatography/mass spectrometry, authentic GGA was eluted at a retention time of around 18 min as a negative ion of m/z 303.4. With healthy volunteers, plasma GGA was detected prior to the tablet intake and its concentrations were increased at 2 h after its intake and maintained at higher level until 4 h, suggesting an efficient bioavailability of preformed GGA in the turmeric tablets through oral administration. These results indicated that GGA in the turmeric tablet was absorbed as an intact form from intestinal mucosa. The present study provides a clue to conduct a research for cancer preventive roles of GGA in a number of spices. PMID:20490321

Mitake, Maiko; Ogawa, Hiroko; Uebaba, Kazuo; Shidoji, Yoshihiro

2010-01-01

311

21 CFR 520.1696d - Penicillin V potassium tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Penicillin V potassium tablets. 520.1696d...ANIMAL DRUGS § 520.1696d Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to...

2011-04-01

312

21 CFR 520.1696d - Penicillin V potassium tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Penicillin V potassium tablets. 520.1696d...ANIMAL DRUGS § 520.1696d Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to...

2012-04-01

313

21 CFR 520.1696d - Penicillin V tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Penicillin V tablets. 520.1696d Section...NEW ANIMAL DRUGS § 520.1696d Penicillin V tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125...

2013-04-01

314

21 CFR 520.1696d - Penicillin V tablets.  

...2014-04-01 2014-04-01 false Penicillin V tablets. 520.1696d Section...NEW ANIMAL DRUGS § 520.1696d Penicillin V tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125...

2014-04-01

315

21 CFR 520.1696d - Penicillin V potassium tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Penicillin V potassium tablets. 520.1696d...ANIMAL DRUGS § 520.1696d Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to...

2010-04-01

316

21 CFR 520.82a - Aminopropazine fumarate tablets.  

Code of Federal Regulations, 2010 CFR

... § 520.82a Aminopropazine fumarate tablets. (a) Specifications. The drug is in tablet form. Each tablet contains aminopropazine fumarate equivalent...weight. The dosage can be repeated every 12 hours, as indicated.1 (3)...

2010-04-01

317

21 CFR 520.434 - Chlorphenesin carbamate tablets.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Chlorphenesin carbamate tablets. 520.434 ...FORM NEW ANIMAL DRUGS § 520.434 Chlorphenesin carbamate tablets. (a) Specifications...Each tablet contains 400 milligrams of chlorphenesin carbamate. (b) Sponsor....

2012-04-01

318

21 CFR 520.434 - Chlorphenesin carbamate tablets.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Chlorphenesin carbamate tablets. 520.434 ...FORM NEW ANIMAL DRUGS § 520.434 Chlorphenesin carbamate tablets. (a) Specifications...Each tablet contains 400 milligrams of chlorphenesin carbamate. (b) Sponsor....

2011-04-01

319

21 CFR 520.434 - Chlorphenesin carbamate tablets.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Chlorphenesin carbamate tablets. 520.434 ...FORM NEW ANIMAL DRUGS § 520.434 Chlorphenesin carbamate tablets. (a) Specifications...Each tablet contains 400 milligrams of chlorphenesin carbamate. (b) Sponsor....

2013-04-01

320

21 CFR 520.434 - Chlorphenesin carbamate tablets.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Chlorphenesin carbamate tablets. 520.434 ...FORM NEW ANIMAL DRUGS § 520.434 Chlorphenesin carbamate tablets. (a) Specifications...Each tablet contains 400 milligrams of chlorphenesin carbamate. (b) Sponsor....

2010-04-01

321

21 CFR 520.434 - Chlorphenesin carbamate tablets.  

...2014-04-01 2014-04-01 false Chlorphenesin carbamate tablets. 520.434 ...FORM NEW ANIMAL DRUGS § 520.434 Chlorphenesin carbamate tablets. (a) Specifications...Each tablet contains 400 milligrams of chlorphenesin carbamate. (b) Sponsor....

2014-04-01

322

Systemic Absorption of Rifamycin SV MMX Administered as Modified-Release Tablets in Healthy Volunteers?  

PubMed Central

The new oral 200-mg rifamycin SV MMX modified-release tablets, designed to deliver rifamycin SV directly into the colonic lumen, offer considerable advantages over the existing immediate-release antidiarrheic formulations. In two pharmacokinetics studies of healthy volunteers, the absorption, urinary excretion, and fecal elimination of rifamycin SV after single- and multiple-dose regimens of the new formulation were investigated. Concentrations in plasma of >2 ng/ml were infrequently and randomly quantifiable after single and multiple oral doses. The systemic exposure to rifamycin SV after single and multiple oral doses of MMX tablets under fasting and fed conditions or following a four-times-a-day (q.i.d.) or a twice-a-day (b.i.d.) regimen could be considered negligible. With both oral regimens, the drug was confirmed to be very poorly absorbable systemically. The amount of systemically absorbed antibiotic excreted by the renal route is far lower than 0.01% of the administered dose after both the single- and multiple-dose regimens. The absolute bioavailability, calculated as the mean percent ratio between total urinary excretion amounts (?Xu) after a single intravenous injection and after a single oral dose under fasting conditions, was 0.0410 ± 0.0617. The total elimination of the unchanged rifamycin SV with feces was 87% of the administered oral dose. No significant effect of rifamycin SV on vital signs, electrocardiograms, or laboratory parameters was observed. PMID:21402860

Di Stefano, A. F. D.; Rusca, A.; Loprete, L.; Dröge, M. J.; Moro, L.; Assandri, A.

2011-01-01

323

Influence of fentanyl and morphine on intestinal circulation  

SciTech Connect

The influence of fentanyl and morphine on the intestinal circulation was evaluated in an isolated loop preparation in 37 dogs anesthetized with pentobarbital intravenously. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mm Hg. A mixture of /sup 86/Rb and 9-micron spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A strong correlation was found between the clearances of rubidium and microspheres (r = 0.97, P less than 0.0001), suggesting that the shunting of 9-micron spheres through the intestines reflects the shunting of blood through nonnutritive vessels. Intravenous fentanyl decreased oxygen uptake (O/sub 2/up), and vascular resistance (VR), and increased blood flow (BF), rubidium and microsphere clearances (Cl-Rb, Cl-Sph, respectively), and permeability--surface area product (PS) in a dose-related fashion. Intravenous morphine in a dose of 1 mg X kg-1 increased Cl-Rb (nutritive BF) without changes in total (nutritive and nonnutritive) BF. This increase in nutritive BF is probably related to morphine-induced histamine release. Morphine in a dose of 5 mg X kg-1 was accompanied by vasoconstriction that was completely abolished by alpha-adrenoceptor blockade. The data suggest that morphine-induced intestinal vasoconstriction is mediated via a release of epinephrine, apparently from the adrenal medulla. It is concluded that changes in the intestinal circulation during anesthesia with narcotics might play a certain role in the cardiovascular homeostasis during anesthesia and surgery. An increase in oxygen content in portal venous blood, resulting from a decrease in intestinal oxygen uptake, should facilitate hepatic oxygenation.

Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

1985-06-01

324

In vitro evaluation of the potential role of sulfite radical in morphine-associated histamine release  

PubMed Central

Background Intravenous morphine use is associated with elevated histamine release leading to bronchoconstriction, edema and hemodynamic instability in some patients. This study evaluated the possibility that sulfite, which is present as a preservative in many morphine preparations, might contribute to histamine release in vitro. Results The human mast cell line, HMC-1, was exposed to various morphine concentrations, in the absence of sulfite, under cell culture conditions. Clinically attained concentrations of morphine (0.018?g/ml and 0.45?g/ml) did not cause increased histamine release from mast cells. There was a significant increase in histamine release when the morphine concentration was increased by 1184-fold (668?g/ml morphine). Histamine release from mast cells exposed to morphine and/or sulfite required the presence of prostaglandin H synthetase. Histamine release in experiments using sulfite-containing morphine solutions was not statistically different from that observed in morphine-only solutions. Conclusion Sulfite in sulfite-containing morphine solutions, at concentrations seen clinically, is not responsible for histamine release in in vitro experiments of the human mast cell line, HMC-1. This does not preclude the fact that sulfite may lead to elevation of histamine levels in vivo. PMID:15469613

Gordon, Emma M; Myers, Carolyn; Blumer, Jeffrey

2004-01-01

325

Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats  

SciTech Connect

The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-(/sup 14/C)xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in /sup 14/CO/sub 2/ excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an ..cap alpha../sub 2/-adrenergic agonist.

Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

1987-04-01

326

Effects of atrial natriuretic peptide on acute and chronic effects of morphine.  

PubMed

Atrial natriuretic peptide (ANP) is known to participate in different vegetative functions. The aim of the present study was to investigate the influence of ANP on nociception itself, pain sensitivity to morphine, and the development of acute and chronic tolerance to morphine. Morphine withdrawal signs were also evaluated by injecting naloxone. In adult, male NMRI mice, ANP administered SC or ICV did not affect pain sensitivity itself in a heat-radiant tail-flick test. Peptide treatment, however, depressed the acute nociceptive effect of a single dose of morphine (4 mg/kg, SC) after both SC (20-200 ng/animal) and ICV (5, 10, 20, or 200 ng/animal) ANP administration. ANP given SC and ICV attenuated the development of acute morphine tolerance. Acute morphine tolerance was assessed by giving a bolus injection of morphine (60 mg/kg) 24 h before the pain sensitivity to a challenge dose of morphine (4 mg/kg) was measured. ICV treatment with ANP also blocked the development of chronic morphine tolerance, but did not affect the appearance of naloxone-precipitated withdrawal syndromes. ANP seems to act differently on the development of tolerance to and dependence upon morphine. PMID:1409804

Azarov, A V; Szabó, G; Telegdy, G

1992-09-01

327

Olive ( Olea europaea L.) leaf extract elicits antinociceptive activity, potentiates morphine analgesia and suppresses morphine hyperalgesia in rats  

Microsoft Academic Search

Aim of the studyOlive (Olea europaea) leaves are used as anti-rheumatic, anti-inflammatory, antinociceptive, antipyretic, vasodilatory, hypotensive, antidiuretic and hypoglycemic agents in traditional medicine. Recently, it has been shown that olive leaf extract (OLE) has calcium channel blocker property; however, its influences on nociceptive threshold and morphine effects have not yet been clarified.

Saeed Esmaeili-Mahani; Maryam Rezaeezadeh-Roukerd; Khadije Esmaeilpour; Mehdi Abbasnejad; Bahram Rasoulian; Vahid Sheibani; Ayat Kaeidi; Zahra Hajializadeh

2010-01-01

328

1H-NMR microscopy of tablets.  

PubMed

A 1H-nuclear magnetic resonance (NMR) microscopy method was utilized for the first time to determine the porosity distribution of physically intact tablets. The main advantage of this newly developed method was that porosity cross sections through whole tablets or specific locations could be obtained without mechanically destroying the tested tablet. This was achieved by filling tablet cavities with silicone oil under vacuum. The amount of silicone oil locally within the tablet was then determined by 1H-NMR microscopy, revealing the inverse inner structure. To reduce the measuring time, a paramagnetic gadolinium complex was added to the silicone oil. The cross sectional signals produced by 1H-NMR microscopy through the tablet were transformed into a color image by a specially designed computer graphic program. To improve the signal-noise ratio an algorithm of 3D-filtering was introduced. The maximal spatial resolution achieved with this method was about 95 microns for a cube's edge length corresponding to some 380,000 positions in a 9-mm-diameter compression-coated tablet. Uneven porosity distributions within tablets, cracks, or cavities could be visualized with this newly developed method. Different compaction mechanisms were observed with plastic- or brittle-type tablets. The different states of densification during compaction of powders could be detected. The integrity of compression coatings was determined to be dependent on the pressure load and the location of the core within the coat. PMID:7616364

Nebgen, G; Gross, D; Lehmann, V; Müller, F

1995-03-01

329

Evaluation of named binders in Rauwolfia vomitoria root tablets.  

PubMed

Some physical properties of Rauwolfia vomitoria root tablets were studied. Tablet characteristics studied were: weight uniformity, tensile strength, friability, disintegration time and content uniformity. Tablet property varied depending on the type and concentration of the binder. The tablets had type and concentration of the binder. The tablets had acceptable hardness and friability profiles. Although tablets containing 150 mg R. vomitoria root had lower tensile strength values. All the tablets passed the B.P. disintegration time test of 15 min. Moreover tablets containing 150 mg R. vomitoria root disintegrated under 1 min. at 4% w/w binder concentration. PMID:10961024

Onunkwo, G C

2000-01-01

330

Pharmacokinetics study of bio-adhesive tablet of Panax notoginseng saponins  

Microsoft Academic Search

Panax notoginseng saponin (PNS) is the main active gradient of Chinese traditional medicine Panax notoginseng. Although its\\u000a prominent therapeutic efficacy has been demonstrated by various researchers, the broader application is restricted by the\\u000a low bioavailability of PNS. This article aims to discuss PNS's plasma pharmacokinetics after oral administration of bio-adhesive\\u000a tablet of PNS to beagle dogs and improve its bioavailability

Hanzhou Feng; Wei Chen; Chunyan Zhu

2011-01-01

331

The effect of chitosan on the stability and morphological parameters of tablets with Epilobium parviflorum Schreb. extract.  

PubMed

The study is a continuation of research on manufacturing oral solid drug form containing extract from Epilobium parviflorum Schreb. This study aims at investigating the usefulness of selected high-molecular substances with particular consideration of chitosan (Ch), silicified microcrystalline cellulose (Prosolv) and croscarmellose sodium (Vivasol) as a carrier of E. parviflorum Schreb. extract in oral solid drug form in the process of direct tableting. In one series the alternative technological process (with initial granulation) was applied. The polymer carriers of extract were selected so as to obtain shorter disintegration time in relation to the earlier published studies and stability after longer time of storage. The effect of chitosan was estimated on selected morphological parameters of practical relevance during storage. The obtained results allow to state that the applied high-molecular adjuvant substances proved to be useful in adequate proportions in the production of tablets from dry extract from Epilobium parviflorum Schreb. through direct pressing of the tablet mass. The tablet properties in all series were in accordance with obligatory standards also after longer time of storage (12-month). The tablets formed from E. parviflorum Schreb. extract with chitosan can be included into preparations of sustained release time of the biologically active substances. PMID:18251200

Marczy?ski, Zbigniew; Bodek, Kazimiera Henryka

2007-01-01

332

Memantine and dizocilpine interactions with antinociceptive or discriminative stimulus effects of morphine in rats after acute or chronic treatment with morphine  

PubMed Central

Rationale Memantine is a N-methyl-d-aspartic acid receptor (NMDAR) channel blocker that binds to dizocilpine sites and appears well tolerated during chronic use. Published studies suggest NMDAR antagonists prevent development of tolerance to effects of morphine by blocking NMDAR hyperactivation. Objectives We sought to compare effects of memantine to those of the more frequently studied dizocilpine and to evaluate memantine as a potential adjunct to modify tolerance to mu-opioid receptor agonists. Methods Sprague–Dawley rats were trained to discriminate morphine (3.2 mg/kg) and saline under fixed ratio 15 schedules of food delivery. Potency and maximal stimulus or rate-altering effects of cumulative doses of morphine were examined 30 min after pretreatment with dizocilpine (0.032–0.1 mg/kg) or memantine (5–10 mg/kg) and after chronic treatment with combinations of dizocilpine or memantine and morphine, 10 mg/kg twice daily, for 6 to 14 days. Effects of dizocilpine or memantine on morphine antinociception were examined in a 55 °C water tail-withdrawal assay with drug treatments parallel to those in discrimination studies. Results Acutely, memantine attenuated while dizocilpine potentiated the stimulus and antinociceptive effects of morphine. Neither chronic dizocilpine nor memantine blocked tolerance to the stimulus effects of morphine. In contrast, combined-treatment with dizocilpine (0.1 mg/kg) blocked tolerance to antinociceptive effects of lower (0.1?3.2 mg/kg) but not higher doses of morphine, whereas memantine did not block tolerance. Conclusions Memantine and dizocilpine interacted differently with morphine, possibly due to different NMDAR binding profiles. The lack of memantine-induced changes in morphine tolerance suggests memantine may not be a useful adjunct in chronic pain management. PMID:22864944

Chen, Yukun; Evola, Marianne

2013-01-01

333

Involvement of cyclic AMP systems in morphine physical dependence in mice: prevention of development of morphine dependence by rolipram, a phosphodiesterase 4 inhibitor  

PubMed Central

In this study, we examined whether morphine dependence was inhibited by rolipram, a cyclic AMP selective phosphodiesterase inhibitor in mice, since a role for the cyclic AMP systems in the development of morphine dependence has been reported. Mice, which received morphine (10?mg?kg?1 s.c.) twice a day for 5 days showed withdrawal syndromes such as jumping, rearing and forepaw tremor following naloxone challenge (5?mg?kg?1 i.p.) on the 6th day. Such mice exhibited a significant elevation of cyclic AMP levels in the thalamus compared to control mice. However, co-administration of rolipram (1?mg?kg?1 i.p.) with morphine for 5 days significantly attenuated the severity of the withdrawal syndrome and the increase in the cyclic AMP levels after the administration of naloxone. In naïve mice, acute morphine treatment (10?mg?kg?1 s.c.) decreased cyclic AMP levels in the thalamus and cerebral cortex 10?min later. The decrease of cyclic AMP levels induced by acute morphine treatment was blocked by co-administration of rolipram (1?mg?kg?1 i.p.). However, acute rolipram did not affect the naloxone-precipitated morphine withdrawal syndrome. These results suggest that the elevation of the cyclic AMP levels is involved in the development of morphine withdrawal syndrome and that blockade of the morphine-induced reduction of cyclic AMP levels by chronic rolipram inhibits the development of dependence and the behavioural and biochemical changes induced by naloxone. Furthermore, rolipram may be a useful drug for attenuating the development of morphine dependence. PMID:11226142

Mamiya, Takayoshi; Noda, Yukihiro; Ren, Xiuhai; Hamdy, Moustafa; Furukawa, Shoei; Kameyama, Tsutomu; Yamada, Kiyofumi; Nabeshima, Toshitaka

2001-01-01

334

Modulation of ethanol-intake by morphine: Evidence for a central site of action  

SciTech Connect

Previous studies have shown that subcutaneous administration of low doses of morphine increase, while subcutaneous naloxone decreases, ethanol-intake in rats. However, the site of action of morphine modulation of ethanol-intake remains unclear. In an attempt to elucidate this issue, seven graded doses of morphine were given intracerebroventricularly to rats 15 min prior to an opportunity to consume water and sweetened alcoholic beverage for 2 hr. Two lower doses of intracerebroventricular morphine reliably increased ethanol-intake, while higher doses decreased intake of water. Preference ratios were reliably increased by morphine doses of 1 {mu}g and higher. The present data provide support for a central site of morphine modulation of ethanol-intake.

Wild, K.D.; Reid, L.D. (Rensselaer Polytechnic Institute, Troy, NY (USA))

1990-01-01

335

Drug Testing in Oral Fluid  

PubMed Central

Over the last decade there have been considerable developments in the use of oral fluid (saliva) for drug testing. Oral fluid can provide a quick and non-invasive specimen for drug testing. However, its collection may be thwarted by lack of available fluid due to a range of physiological factors, including drug use itself. Food and techniques designed to stimulate production of oral fluid can also affect the concentration of drugs. Current applications are mainly focused on drugs of abuse testing in employees at workplaces where drug use has safety implications, in drivers of vehicles at the roadside and in other situations where drug impairment is suspected. Testing has included alcohol (ethanol) and a range of clinical tests eg antibodies to HIV, therapeutic drugs and steroids. Its main application has been for testing for drugs of abuse such as the amphetamines, cocaine and metabolites, opioids such as morphine, methadone and heroin, and for cannabis. Oral fluid concentrations of basic drugs such as the amphetamines, cocaine and some opioids are similar or higher than those in plasma. Tetrahydrocannabinol (THC), the major species present from cannabis use, displays similar concentrations in oral fluid compared to blood in the elimination phase. However, there is significant local absorption of the drug in the oral cavity which increases the concentrations for a period after use of drug. Depot effects occur for other drugs introduced into the body that allow local absorption, such as smoking of tobacco (nicotine), cocaine, amphetamines, or use of sub-lingual buprenorphine. Screening techniques are usually an adaptation of those used in other specimens, with an emphasis on the parent drug since this is usually the dominant species present in oral fluid. Confirmatory techniques are largely based on mass spectrometry (MS) with an emphasis on Liquid Chromatography-Mass Spectrometry (LC-MS), due to low sample volumes and the low detection limits required. Drug testing outside laboratory environments has become widespread and provides presumptive results within minutes of collection of specimens. This review focuses on the developments, particularly over the last 10 years, and outlines the roles and applications of testing for drugs in oral fluid, describes the difficulties associated with this form of testing and illustrates applications of oral fluid testing for specific drugs. PMID:17268583

Drummer, Olaf H

2006-01-01

336

Enhanced bioavailability of buspirone hydrochloride via cup and core buccal tablets: formulation and in vitro/in vivo evaluation.  

PubMed

This work aims to prepare sustained release buccal mucoadhesive tablets of buspirone hydrochloride (BH) to improve its systemic bioavailability. The tablets were prepared according to 5×3 factorial design where polymer type was set at five levels (carbopol, hydroxypropyl methylcellulose, sodium alginate, sodium carboxymethyl cellulose and guar gum), and polymer to drug ratio at three levels (1:1, 2:1 and 3:1). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h) and time for release of 50% BH (T(??%)) were chosen as dependent variables. Additional BH cup and core buccal tablets were prepared to optimize BH release profile and make it uni-directional along with the tablets mucoadhesion. Tablets were evaluated in terms of content uniformity, weight variation, thickness, diameter, hardness, friability, swelling index, surface pH, mucoadhesion strength and time and in vitro release. Cup and core formula (CA10) was able to adhere to the buccal mucosa for 8h, showed the highest Q8h (97.91%) and exhibited a zero order drug release profile. Pharmacokinetic study of formula CA10 in human volunteers revealed a 5.6 fold increase in BH bioavailability compared to the oral commercial Buspar® tablets. Conducting level A in vitro/in vivo correlation showed good correlation (r²=0.9805) between fractions dissolved in vitro and fractions absorbed in vivo. PMID:24412520

Kassem, Mohamed A A; Elmeshad, Aliaa N; Fares, Ahmed R

2014-03-10

337

Oral Insulin  

Microsoft Academic Search

Oral insulin is an exciting area of research and development in the field of diabetology. This brief review covers the various approaches used in the development of oral insulin, and highlights some of the recent data related to novel oral insulin preparation.

Sanjay Kalra; Bharti Kalra; Navneet Agrawal

2010-01-01

338

Oral Insulin  

PubMed Central

Oral insulin is an exciting area of research and development in the field of diabetology. This brief review covers the various approaches used in the development of oral insulin, and highlights some of the recent data related to novel oral insulin preparation. PMID:21059246

2010-01-01

339

Oral Medication  

MedlinePLUS

... over-the-counter items. Explore: Oral Medication How Much Do Oral Medications Cost? Save money by finding the right type and ... Options? Is There a Danger of Interactions? How Much Do Oral Medications Cost? We Can Help (Long) - we-can-help-long. ...

340

Effects of neomycin on the development of tolerance to morphine antinociception  

Microsoft Academic Search

The effects of neomycin on the development of tolerance to morphine antinociception were examined in mice. Because neomycin did not readly cross blood brain barrier, we examined the effects of neomycin following systemic, intracerebroventricular (i.c.v.) and intrathecal (i.t.) injections on the morphine tolerance. Daily subcutaneous (s.c.), i.c.v. and i.t. injections of morphine produced tolerance regardless of route of administration. Both

Ahmet Do?rul; Özgür Ye?ilyurt; A?k?n I??mer

2001-01-01

341

Morphine protects SH-SY5Y human neuroblastoma cells against Dickkopf1-induced apoptosis.  

PubMed

Morphine is used to relieve pain in patients with cancer in terminal phases. Dickkopf?1 (DKK1), a secreted protein, is a negative regulator of the Wnt/??catenin signaling pathway. Morphine and DKK1 are associated with tumorigenesis. However, to the best of our knowledge, there is no study evaluating the effects of these two factors simultaneously. In the present study, the effects of morphine and DKK1 on neuroblastoma cells in vivo and in vitro were evaluated. To establish the in vitro effects of DKK1 and morphine, human neuroblastoma SH?SY5Y cells were transfected with a DKK1?expressing plasmid and cell migration, apoptosis, migration and invasion were evaluated prior to and following morphine treatment. The results indicated that DKK1 induced apoptosis and inhibited the mobility of neuroblastoma cells and that morphine attenuated these DKK1?induced effects. To evaluate the effects of DKK1 and morphine in vivo, a mouse model of neuroblastoma was established, where mice bearing tumors of native SH-SY5Y cells were injected with DKK1. Tumor size, spatial memory and survival rate were investigated in untreated, DKK1?treated and DKK1+morphine?treated mice. Water maze and T?maze tests were performed, which revealed that DKK1?treated mice exhibited a better memory than DKK1 + morphine?treated mice. The expression of DKK1 in established xenografted tumors was associated with decreased tumor size and an increased survival rate, whereas morphine reversed these effects. Furthermore, it was confirmed that morphine and DKK1 take effect, at least in part, via the Wnt/??catenin signaling pathway. The results of the present study indicate that morphine may protect neuroblastoma cells and thus, it may be used in neuroblastoma patients. PMID:25370481

Wang, Kun-Peng; Bai, Yu; Wang, Jian; Zhang, Jin-Zhen

2015-02-01

342

The effects of NMDA receptor antagonists on acute morphine antinociception in mice  

Microsoft Academic Search

Summary.  ?Antagonists of the N-methyl-d-aspartate (NMDA) receptor complex inhibit the development of tolerance to antinociceptive effects of morphine and upon acute\\u000a administration, influence morphine antinociceptive activity. The analysis of numerous studies investigating acute interaction\\u000a between NMDA receptor antagonists and morphine in mice indicate a variety of procedural differences and reveal that these\\u000a compounds may potentiate, attenuate and produce no effect on

E. Kozela; P. Popik

2002-01-01

343

Agmatine modulates neuroadaptations of glutamate transmission in the nucleus accumbens of repeated morphine-treated rats.  

PubMed

It has been proved that agmatine inhibits opioid dependence, yet the neural mechanism remains unclear. In the present study, the effect of agmatine on the neuroadaptation of glutamate neurotransmission induced by morphine dependence, including changes of the extracellular glutamate level and glutamate receptors in the nucleus accumbens was investigated. We found that agmatine (2.5-20mg/kg, s.c.) inhibited development of morphine dependence, which was consistent with our previous report. In rats repeatedly treated with morphine, the glutamate level in the nucleus accumbens dialysate was markedly increased after naloxone-precipitated withdrawal. When agmatine (20mg/kg, s.c.) was co-pretreated with morphine or was applied before naloxone-precipitated withdrawal, this elevation of the extracellular glutamate level was inhibited. In the synaptosome model, repeated morphine treatment and naloxone precipitation induced an increase in glutamate release, while agmatine (20mg/kg, s.c.) co-pretreated with morphine reversed the increase of glutamate release. However, neither morphine or agmatine treatment alone nor morphine and agmatine co-administration had any influence on [3H]-glutamate uptake. It indicated that the elevation of the glutamate level in the nucleus accumbens might be caused by the increase of glutamate release of synaptosome in the withdrawal conditions of morphine-dependent rat. Furthermore, agmatine concomitant treatment with morphine entirely abolished the up-regulation of the NR1 subunit of N-methyl-d-aspartate (NMDA) receptors in the nucleus accumbens in repeated morphine-treated rats. Taken together, the present study demonstrated that agmatine could modulate the neuroadaptations of glutamate transmission in the nucleus accumbens in the case of morphine dependence, including modulating extracellular glutamate concentration and NMDA receptor expression. PMID:20950603

Wang, Xiao-Fei; Wu, Ning; Su, Rui-Bin; Lu, Xin-Qiang; Liu, Yin; Li, Jin

2011-01-10

344

Evaluation of morphine effect on tumour angiogenesis in mouse breast tumour model, EATC  

Microsoft Academic Search

Breast cancer is the leading cause of death among women, and morphine is used to relieve the pain of patients with cancer.\\u000a The data on the effects of morphine on tumour growth and angiogenesis are contradictory. We determined in mouse breast cancer\\u000a model whether analgesic doses of morphine would affect tumour angiogenesis, and then the correlation between microvessel density\\u000a (MVD),

Funda UstunGulay; Gülay Durmus-Altun; Semsi Altaner; Nermin Tuncbilek; Cem Uzal; Sakir Berkarda

345

Chronic morphine exposure induces degradation of receptive field pro- perties of LGN cells in cats1  

Microsoft Academic Search

Aim: To investigate the effect of chronic morphine exposure on the receptive field properties of lateral geniculate nucleus (LGN) neurons in cats. Methods: Cats were injected with morphine (10 mg\\/kg) or saline twice daily, for 10 d. Subsequently, extracellular single-unit recording techniques were used to examine the sensitivity of LGN neurons to visual stimuli in chronic morphine-treated and saline-treated cats.

Li-hua HE; Guang-xing LI; Xiang-rui LI; Yi-feng ZHOU

346

Dual effect of morphine in long-term social memory in rat  

PubMed Central

Background and Purpose Bimodal dose–response relationships have been demonstrated in animals and humans following morphine administration. We examined if systemic administration of morphine, in extremely low (?g) and high (mg, analgesic) doses, changed the learning process. Experimental Approach In the social learning test, an adult rat investigates a juvenile. The juvenile is submitted to a second encounter after a few days and investigation by the adult should be reduced. Morphine was administered before the first encounter between rats, and the critical test was performed 24, 72 or 168 h later, when animals were re-exposed to each other, in the absence of morphine. Key Results Low doses of morphine, comparable with endogenous brain concentrations, enhanced long-term memory recognition; while high doses did the reverse, indicating the adult failed to recognize the juvenile. Recognition of a familiar rat appeared to be mediated within the brain accessory olfactory bulb (AOB) by an opioid system intrinsic to the olfactory system through ?-opioid receptors (MORs). At this supraspinal site, the PLC/PKC signalling pathway was activated by extremely low morphine doses. Conclusions and Implications Morphine treatment administration may either disrupt or facilitate social memory, depending on the dose, extending to memory formation the bimodal effects of morphine previously shown in pain. Social memory formation elicited by extremely low morphine doses, was mediated within the AOB by an opioid system, intrinsic to the olfactory system through MORs. PMID:23171436

Bianchi, Enrica; Menicacci, Cristina; Ghelardini, Carla

2013-01-01

347

Inhibitory effect of low-dose pentazocine on the development of antinociceptive tolerance to morphine  

Microsoft Academic Search

Purpose  The development of antinociceptive tolerance to morphine is one of the major problems in its clinical use. Therefore, exploring\\u000a effective measures to prevent morphine tolerance is of great clinical relevance. We evaluated whether pentazocine could prevent\\u000a morphine tolerance in mice.\\u000a \\u000a \\u000a \\u000a Methods  Five groups of male ICR mice received repeated subcutaneous (s.c.) injections of morphine at a high dose (10 mg·kg?1) or

Shunsuke Chiba; Masakazu Hayashida; Masanobu Yoshikawa; Haihua Shu; Tomoki Nishiyama; Yoshitsugu Yamada

2009-01-01

348

Blockade and reversal of spinal morphine tolerance by P2X3 receptor antagonist.  

PubMed

In recent years, studies have substantiated the view that P2X3 receptors play a part in the generation and transmission of purinergic signals in inflammatory and chronic neuropathic pain. Data have also been presented to suggest that the process of P2X3 receptor antagonism inhibits inflammatory hyperalgesia, involving the spinal opioid system. The aim of this study was to investigate the effect of the selective P2X3 receptor antagonist A-317491 on the development of antinociceptive tolerance to chronic morphine administration in mice. Daily systemic injection of A-317491 attenuated the morphine-induced antinociceptive tolerance to von Frey and thermal stimuli. Repeated morphine injections alone led to a significant rightward shift in the morphine dose-response curve compared with that with A-317491. A single dose of A-317491 also showed a reversal effect in morphine-tolerant mice. In a withdrawal test, co-administration of A-317491 and morphine also reduced the naloxone-induced withdrawal symptoms compared with the morphine-alone group. Thus, we propose that the P2X3 receptor is involved in the process of morphine antinociceptive tolerance and may be a new therapeutic target in the prevention of tolerance to morphine-induced antinociception. PMID:25350728

Ma, Xiaqing; Xu, Tao; Xu, Hao; Jiang, Wei

2014-10-27

349

Storage temperature effect on the stability of morphine and codeine in urine.  

PubMed

Urine samples collected from one laboratory volunteer and five alleged heroin addicts are prepared (without preservatives) in 5-mL aliquots in glass culture tubes and stored at room, refrigerator, and freezer temperatures. Total morphine, total codeine, free morphine, and free codeine in these samples are analyzed at 30-day intervals for an 11-month period. Total morphine and total codeine concentration decreases are observed for all specimens in all storage conditions. For samples stored in the refrigerator and freezer, similar concentration decrease patterns are observed for total morphine and total codeine, and the decreases range from approximately 10 to 40%. The concentrations of free morphine and free codeine show slight but steady increases. For samples stored at room temperature, large decreases of total morphine are observed for three out of 10 specimens, and total codeine and total morphine concentrations (in seven other specimens) show a decrease pattern similar to that observed for the freezer and refrigerator storage conditions. Three concentration change patterns are observed for free morphine: The type I pattern follows the same decrease pattern observed for freezer and refrigerator storage conditions; the type II pattern shows free morphine increases (after 30-90 days of storage) that remain relatively high for the entire 11-month period; and the type III pattern shows initial increases, followed by gradual decreases to levels that are comparable with the specimens' respective initial concentrations. Free codeine concentrations show slight and steady increases for the entire 11-month period in all specimens. PMID:7500612

Lin, D L; Liu, H; Chen, C Y

1995-09-01

350

[Morphine by external route, prescribed to Heinrich Heine by David Gruby].  

PubMed

The exhibition held in Paris commemorating the bicentenial of Heinrich Heine showed three prescriptions by Dr. D. Gruby, through which morphine was prescribed for the poet by external route. The use of morphine was justified in a patient with unrelieved pain caused by neurosyphilis during the last twelve years of his life. This way of morphine administration (endemic method) was quite popular between 1830 and 1860. The process consisted in stripping the derm with the help of a vesicant and in applying directly on it morphine salts crystals. Several authors commented the interest of this way of administration rather uncomfortable for the patient but apparently very effective. PMID:11625475

Chast, F

1998-01-01

351

Agmatine blocks acquisition and re-acquisition of intravenous morphine self-administration in rats.  

PubMed

Our previous studies showed that agmatine inhibits morphine-induced conditioned place preference, locomotor sensitization and drug discrimination in rats. In the present study, we investigated the effects of agmatine on intravenous morphine self-administration in rats. At a dose of 80 mg/kg/infusion, agmatine did not substitute for intravenous morphine (0.5 mg/kg/infusion) self-administration, suggesting that agmatine itself has no reinforcing effect. However, pretreatment with agmatine (40 or 80 mg/kg, i.g.) significantly inhibited the acquisition of intravenous morphine self-administration as assessed by the nose-poke response and morphine intake. The mean number of days required to meet the acquisition criteria for intravenous morphine self-administration was significantly prolonged. After acquisition of intravenous morphine self-administration, chronic administration of agmatine (40 or 80 mg/kg x 30 days, bid, i.g.) during the extinction period significantly prevented the re-acquisition of intravenous morphine self-administration. The ability of agmatine to inhibit the acquisition and re-acquisition of intravenous morphine self-administration suggests a possible use of agmatine in the treatment of opioid dependence. PMID:19328824

Su, Rui-Bin; Wang, Wei-Ping; Lu, Xin-Qiang; Wu, Ning; Liu, Zhi-Min; Li, Jin

2009-06-01

352

[Calorimetric evaluation of directly compressed tablets].  

PubMed

The paper studies the effect of the type of the disintegrating substance and the lubricant on the destruction heat of tablet materials and tablets. Destruction heat was determined by means of isoperibolic calorimetry. Tablet materials and tablets contained Avicel PH 101 as the dry binder, 10% of Primojel, Ac-Di-Sol, or Polyplasdone XL as disintegrating substances, and 5% of magnesium strearate or sodium laurylsulfate as the lubricants. The sum of destruction heats of the individual auxiliary substances equalled the found values in tablet materials and tablets. In tablets, in contrast to tablet materials, values of destruction heat higher by 57.9% were found. In the disintegrating substances and lubricants tested, the found values of destruction heats were dependent on the values of destruction heats of the individual auxiliary substances. In the disintegrating substances, a linear dependence of the total destruction heat (CDT) on the destruction heat of the disintegrating substances (DTR) was found, given by the relationship CDT = 0.797.DTR + 17.666 with the correlation coefficient r = 0.986. PMID:11242832

Rehula, M; Lavická, J; Musilová, M

2001-01-01

353

Remission of central fever with morphine post traumatic brain injury.  

PubMed

After a brain injury, raised temperature may be due to a regulated readjustment in the hypothalamic 'set-point' in response to inflammation. The purpose of this report is to mention possible implications related to temperature and homeostasis of morphine treatment in a patient with brain injury. During the month previous to her hospitalization in our city she was treated for fever with paracetamol and metamizol without results. After 31 days with similar results, we changed to morphine IV considering the possibility of treating pain and fever. This option was successful and afterwards we changed to fentanyl patches, keeping fever absent. After 100 days of hospitalization, the patient was discharged to her home. PMID:24684128

Mendieta Zerón, Hugo; Arriaga García Rendon, Julio Cesar

2014-01-01

354

CXCR4 Signaling Mediates Morphine-induced Tactile Hyperalgesia  

PubMed Central

Morphine and related compounds are the first line of therapy in the treatment of moderate to severe pain. Over time, individuals taking opioids can develop an increasing sensitivity to noxious stimuli, even evolving into a painful response to previously non-noxious stimuli (opioid-induced hyperalgesia; OIH). The mechanism underlying OIH is not well understood although complex intracellular neural mechanisms, including opioid receptor desensitization and down-regulation, are believed to be major mechanisms underlying OIH. However, OIH may also be associated with changes in gene expression. A growing body of evidence suggests that cellular exposure to mu agonists upregulate chemokines/receptors and recent work from our lab implicates chemokine upregulation in a variety of neuropathic pain behaviors. Here we characterized the degree to which chemokines/receptors signaling is increased in primary afferent neurons of the dorsal root ganglion (DRG) following chronic morphine sulphate treatment and correlated these changes with tactile hyperalgesic behavior in rodents. We demonstrate that mRNA expression of the chemokine, stromal-derived factor-1 (SDF1/CXCL12) is upregulated following morphine treatment in sensory neurons of the rat. The release of SDF1 was found to be constitutive when compared with the activity dependent release of the C-C chemokine, monocyte chemoattractant protein-1 (MCP1/CCL2) in a line of F-11 neuroblastoma-sensory neuron hybrid cells. We further determined that there is pronounced CXCR4 expression in satellite glial cells and following morphine treatment, increased functional CXCR4 expression in sensory neurons of the DRG. Moreover, intraperitoneal administration of the specific CXCR4 antagonist, AMD3100, completely reversed OIH in the rat. Taken together; the data suggest that opioid-induced SDF1/CXCR4 signaling is central to the development of long lasting OIH and that receptor antagonists represent a promising novel approach to the management of the side effects associated with the use of opioids for chronic pain management. PMID:21193025

Wilson, Natalie M.; Jung, Hosung; Ripsch, Matthew S.; Miller, Richard J.

2011-01-01

355

Smartphones and tablets: Reshaping radiation oncologists’ lives  

PubMed Central

Background Smartphones and tablets are new handheld devices always connected to an information source and capable of providing instant updates, they allow doctors to access the most updated information and provide decision support at the point of care. Aim The practice of radiation oncology has always been a discipline that relies on advanced technology. Smartphones provide substantial processing power, incorporating innovative user interfaces and applications. Materials and methods The most popular smartphone and tablet app stores were searched for “radiation oncology” and “oncology” related apps. A web search was also performed searching for smartphones, tablets, oncology, radiology and radiation oncology. Results Smartphones and tablets allow rapid access to information in the form of podcasts, apps, protocols, reference texts, recent research and more. Conclusion With the rapidly changing advances in radiation oncology, the trend toward accessing resources via smartphones and tablets will only increase, future will show if this technology will improve clinical care. PMID:24669308

Gomez-Iturriaga, Alfonso; Bilbao, Pedro; Casquero, Francisco; Cacicedo, Jon; Crook, Juanita

2012-01-01

356

Degradation of morphine in opium poppy processing waste composting.  

PubMed

To investigate morphine degradation and optimize turning frequency in opium poppy processing waste composting, a pilot scale windrow composting trial was run for 55 days. Four treatments were designed as without turning (A1), every 5 days turning (A2), every 10 days turning (A3) and every 15 days turning (A4). During composting, a range of physicochemical parameters including the residual morphine degradation, temperature, pH, and the contents of total C, total N, total P and total K were investigated. For all treatments, the residual morphine content decreased below the detection limit and reached the safety standards after day 30 of composting, the longest duration of high temperature (?50 °C) was observed in A3, pH increased 16.9-17.54%, total carbon content decreased 15.5-22.5%, C/N ratio reduced from 46 to 26, and the content of total phosphorus and total potassium increased slightly. The final compost obtained by a mixture of all four piles was up to 55.3% of organic matter, 3.3% of total nutrient (N, P2O5 and K2O) and 7.6 of pH. A turning frequency of every ten days for a windrow composting of opium poppy processing waste is recommended to produce homogenous compost. PMID:24613672

Wang, Yin Quan; Zhang, Jin Lin; Schuchardt, Frank; Wang, Yan

2014-09-01

357

Phase transformation in thiamine hydrochloride tablets: Influence on tablet microstructure, physical properties, and performance.  

PubMed

The objective of this article was to monitor phase transformation in thiamine hydrochloride, from a nonstoichiometric hydrate (NSH) to a hemihydrate (HH), in stored tablets, prepared both by direct compression and wet granulation, and to relate the storage-induced phase transformation with changes in tablet microstructure, physical properties, and performance. Raman spectroscopy revealed complete NSH ? HH transformation in tablets, within 30 h of storage at 40°C/75% relative humidity. When the tablets were prepared by wet granulation of NSH alone, there was a marked increase in both tablet volume and hardness on storage. However, when microcrystalline cellulose (MCC) was included in granulation, the resulting stored tablets also exhibited a pronounced increase in disintegration time. In contrast, tablets prepared by dry processing via compression of a NSH-MCC physical mixture did not exhibit any changes in properties, despite the in situ solid form conversion. Scanning electron microscopy revealed growth of needle-like HH crystals in all stored tablets and mercury porosimetry revealed considerable changes in the pore size distribution during storage. Longer storage led to crystal growth (Ostwald ripening), causing further gradual but less dramatic changes in properties. The phase transformation and the complex interparticulate associations in the tablet influenced the changes in tablet microstructure, compact physical properties, and product behavior. PMID:22213350

Chakravarty, Paroma; Suryanarayanan, Raj; Govindarajan, Ramprakash

2012-04-01

358

Co-administration of dextromethorphan with morphine attenuates morphine rewarding effect and related dopamine releases at the nucleus accumbens  

Microsoft Academic Search

Morphine is one of the most effective analgesics in clinic to treat postoperative pain or cancer pain. A major drawback of its continuous use is the development of tolerance and dependence. In our previous study we found that a widely used antitussive agent in clinics, dextromethorphan [(DM); also known as a non-competitive N-methyl-d-aspartate (NMDA) antagonist], could prevent the development of

Eagle Y.-K. Huang; Te-Chen Liu; Pao-Luh Tao

2003-01-01

359

Classical conditioning of a morphine abstinence phenomenon, reinforcement of opioid-drinking behavior and “relapse” in morphine-addicted rats  

Microsoft Academic Search

1.For 6-week periods in two studies, rats made tolerant to and maintained on intraperitoneal injection of morphine (200 mg\\/kg) once daily in the morning resided on alternate nights in one end of a 3-compartment linear maze with water for drinking and on the intervening nights in the other end-compartment with etonitazene (10 meg\\/ml) for drinking. On this schedule, temporal contiguity

Abraham Wikler; Frank T. Pescor

1967-01-01

360

Comparison of the antinociceptive response to morphine and morphine-like compounds in male and female Sprague-Dawley rats.  

PubMed

Male rats are more sensitive to the antinociceptive effects of morphine than female rats. This difference is seen across several rat strains using a variety of nociceptive stimuli. However, the literature in regard to sex differences in antinociceptive responses to mu-opioids other than morphine is less consistent. The present study was designed to examine whether there is a structure-activity rationale that determines which mu-opioids will show a differential antinociceptive response between male and female rats. A series of morphinans closely related in structure to morphine, namely, codeine, heroin, hydrocodone, hydromorphone, oxymorphone, and oxycodone, were examined for their antinociceptive activity in male and female Sprague-Dawley rats and compared with the structurally unrelated mu-opioid agonists methadone and fentanyl. Antinociception was measured by the warm-water tail-withdrawal assay. The results show that morphine is more potent in males compared with females > hydromorphone = hydrocodone = oxymorphone, but there was no observable sex difference in the antinociceptive potency of codeine, heroin, oxycodone, methadone, or fentanyl. The potency to stimulate guanosine 5'-O-(3-[35 S]thio)triphosphate ([35S]GTPgammaS) binding and binding affinity of the various morphinans was compared in rat glioma C6 cells expressing the rat mu-opioid receptor; relative efficacy was also compared by stimulation of [35S]GTPgammaS binding in slices of rat brain thalamus. The presence of a sex difference in antinociceptive responsiveness was not related to drug potency, efficacy, or affinity. Consequently, it is likely that differential metabolism of the opioid, possibly by glucuronidation, determines the presence or absence of a sex difference. PMID:16291875

Peckham, Elizabeth M; Traynor, John R

2006-03-01

361

N-methyl-D-aspartate receptors involved in morphine-induced hyperalgesia in sensitized mice.  

PubMed

The aim of this study was to investigate role of the N-Methyl-D-Aspartate (NMDA) receptors in the decrease of morphine analgesia in mice after nociceptive sensitization. We used a hot plate test to assess effects of morphine on pain behavior in male NMRI mice. All drugs were administered through an intraperitoneal route. Sensitization schedule composed of 3-days pre-treatment of morphine (20mg/kg) followed by 5-days washout. The results showed that morphine (5, 7.5, 10 and 15mg/kg) induced a significant analgesia in normal mice. However, the analgesic effects of morphine significantly decreased at higher dose (15mg/kg) in sensitized mice. Injections of either a competitive NMDA receptor antagonist, D-AP5 (0, 0.25, 0.5 and 1mg/kg) or an NMDA receptor channel blocker (30, 60 and 120mg/kg) alone had no effect on pain behavior. However, injections of D-AP5 (1mg/kg), along with morphine over 3-days of the sensitization schedule, significantly prevented the decrease in the analgesic effect of the opioid at doses of 7.5 and 10mg/kg on the hot plate test. Similarly, injections of MgSO4 (120mg/kg), along with morphine over 3-days of the sensitization schedule, significantly prevented the decrease in analgesic effect of morphine at doses of 10 and 15mg/kg. It can be concluded that NMDA receptors are influenced by morphine during the sensitization schedule, which in turn may affect morphine analgesia after the schedule. This may further support the potential effectiveness of NMDA blockade during repeated use of morphine for control of chronic pain. PMID:24842190

Ahmadi, Shamseddin; Golbaghi, Hajar; Azizbeigi, Ronak; Esmailzadeh, Nabaz

2014-08-15

362

The reinforcing effects of chronic D-amphetamine and morphine are impaired in a line of memory-deficient mice  

E-print Network

The reinforcing effects of chronic D-amphetamine and morphine are impaired in a line of memory, we investigated the involvement of calcineurin in the motivational effects of amphetamine and morphine using this line of transgenic mice (CN98). Our results showed that amphetamine and morphine did

Paris-Sud XI, Université de

363

Terahertz Technology: A Boon to Tablet Analysis  

PubMed Central

The terahertz gap has a frequency ranges from ?0.3 THz to ?10 THz in the electromagnetic spectrum which is in between microwave and infrared. The terahertz radiations are invisible to naked eye. In comparison with x-ray they are intrinsically safe, non-destructive and non-invasive. Terahertz spectroscopy enables 3D imaging of structures and materials, and the measurement of the unique spectral fingerprints of chemical and physical forms. Terahertz radiations are produced by a dendrimer based high power terahertz source and spectroscopy technologies. It resolves many of the questions left unanswered by complementary techniques, such as optical imaging, Raman and infrared spectra. In the pharmaceutical industries it enables nondestructive, internal, chemical analysis of tablets, capsules, and other dosage forms. Tablet coatings are a major factor in drug bioavailability. Therefore tablet coatings integrity and uniformity are of crucial importance to quality. Terahertz imaging gives an unparalleled certainty about the integrity of tablet coatings and the matrix performance of tablet cores. This article demonstrates the potential of terahertz pulse imaging for the analysis of tablet coating thickness by illustrating the technique on tablets. PMID:20490288

Wagh, M. P.; Sonawane, Y. H.; Joshi, O. U.

2009-01-01

364

Improving the oral bioavailability of sulpiride by a gastric-retained form in rabbits.  

PubMed

To improve the limited oral bioavailability of sulpiride, a gastric-retained form was developed and evaluated using gastric-emptying-controlled rabbits. The AUC value after oral administration of sulpiride as an aqueous solution was less than that after oral administration of sulpiride original powder. The dissolution was not important as a rate limiting factor for sulpiride oral absorption. Sulpiride was absorbed predominantly from the upper part of the small intestine of the rabbit. A gastric-retained tablet prepared from Carbopol 934P, with sustained-release characteristics, was found to be suitable for improving and extending the oral bioavailability of sulpiride. PMID:8794985

Kohri, N; Naasani, I; Iseki, K; Miyazaki, K

1996-04-01

365

Formulation and optimization of mucoadhesive bilayer buccal tablets of atenolol using simplex design method  

PubMed Central

Introduction: In the present study, mucoadhesive buccal bilayer tablets of atenolol were fabricated with the objective of avoiding first pass metabolism and to improve its bioavailability with reduction in dosing frequency. Hence, the aim of this work was to design oral controlled release mucoadhesive tablets of atenolol and to optimize the drug release profile and bioadhesion. Materials and Methods: Bilayer buccal tablets of atenolol were prepared by direct compression method using simplex method of optimization to investigate the combined effect of hydroxypropyl methylcellulose 15 cps (X1), Carbopol (X2) and mannitol (X3); the in vitro drug release (Y1) and mucoadhesive strength (Y2) were taken as responses. The designed tablets were evaluated for various physical and biological parameters like drug content uniformity, in vitro drug release, short-term stability, and drug- excipient interactions (FTIR). Results: The formulation C containing hydroxypropyl methylcellulose 15 cps (10% w/w of matrix layer), Carbopol 934p (10% w/w of matrix layer) and mannitol (channeling agent, 40% w/w of matrix layer) was found to be promising. This formulation exhibited an in vitro drug release of 89.43% in 9 h along with satisfactory bioadhesion strength (7.20 g). Short-term stability studies on the promising formulation indicated that there are no significant changes in drug content and in vitro dissolution characteristics (P<0.05). IR spectroscopic studies indicated that there are no drug-excipient interactions. PMID:23071958

Shirsand, SB; Suresh, Sarasija; Keshavshetti, GG; Swamy, PV; Reddy, P Vijay Prakash

2012-01-01

366

Controlled release matrix uncoated tablets of enalapril maleate using hpmc alone.  

PubMed

Hydroxy propyl methyl cellulose (HPMC) is generally combined with hydrophobic polymers in fabricating oral controlled solid dosage forms. This study evaluated the utility of diverse grades of HPMC in developing a controlled release formulation for a hydrophilic drug, enalapril maleate. Controlled release uncoated tablets were prepared by direct compression technique. Two grades of HPMC (K100 and K4M) in different proportions were used to prepare the tablets, and were evaluated for physical properties, drug content, in vitro drug release and drug release kinetics as well. All the formulations demonstrated good physical integrity and the drug content were in the official limits. The formulation with HPMC K100 (25 mg/tablet) and K4M (15 mg/tablet) have been found to release the required amount of drug (2.97 mg/h) through out the study period (14 h). The calculated regression coefficients showed higher r(2) value with Higuchi model and zero order kinetics. Given the excellent release profile, the study concluded that HPMC in different grades with low concentration alone can control the enalapril maleate release over a period of time (14 h). PMID:24825968

Nair, Anroop B; Vyas, Hiral; Kumar, Ashok

2010-03-01

367

CONTROLLED RELEASE MATRIX UNCOATED TABLETS OF ENALAPRIL MALEATE USING HPMC ALONE  

PubMed Central

Hydroxy propyl methyl cellulose (HPMC) is generally combined with hydrophobic polymers in fabricating oral controlled solid dosage forms. This study evaluated the utility of diverse grades of HPMC in developing a controlled release formulation for a hydrophilic drug, enalapril maleate. Controlled release uncoated tablets were prepared by direct compression technique. Two grades of HPMC (K100 and K4M) in different proportions were used to prepare the tablets, and were evaluated for physical properties, drug content, in vitro drug release and drug release kinetics as well. All the formulations demonstrated good physical integrity and the drug content were in the official limits. The formulation with HPMC K100 (25 mg/tablet) and K4M (15 mg/tablet) have been found to release the required amount of drug (2.97 mg/h) through out the study period (14 h). The calculated regression coefficients showed higher r2 value with Higuchi model and zero order kinetics. Given the excellent release profile, the study concluded that HPMC in different grades with low concentration alone can control the enalapril maleate release over a period of time (14 h). PMID:24825968

Nair, Anroop B.; Vyas, Hiral; Kumar, Ashok

2010-01-01

368

Differential effects of adult and perinatal lead exposure on morphine-induced locomotor activity in rats  

Microsoft Academic Search

The effects of adult and perinatal lead treatment on the development of locomotor sensitization produced with repeated morphine administration was investigated. In Experiment 1, adult male rats received a diet containing 250 ppm lead acetate or a control diet for 43 days. Animals then received 10 mg\\/kg morphine sulfate or water vehicle (ip) and locomotor activity was monitored for 14

Dennis K Miller; Jack R Nation; Tricia E Jost; Jason B Schell; Gerald R Bratton

2000-01-01

369

Ontogeny of NMDA receptor-mediated morphine tolerance in the postnatal rat  

E-print Network

Ontogeny of NMDA receptor-mediated morphine tolerance in the postnatal rat Hongbo Zhua,1 , Gordon A Abstract N-methyl-D-aspartate (NMDA) receptor antagonists are effective in inhibiting the development of morphine tolerance in adult rats. But NMDA receptors undergo dramatic change during the first few weeks

Barr, Gordon A.

370

Attenuation of morphine-induced delirium in palliative care by substitution with infusion of oxycodone  

Microsoft Academic Search

We have observed among patients of the Southern Community Hospice Programme that up to 25% experience acute delirium when treated with morphine and improve when the opioid is changed to oxycodone or fentanyl. This study aimed to confirm by a prospective trial that oxycodone produces less delirium than morphine in such patients. Oxycodone was administered by a continuous subcutaneous infusion,

Ian Maddocks; Andrew Somogyi; Fay Abbott; Peter Hayball; Deborah Parker

1996-01-01

371

Differentiation by morphine of two types of aggressive behavior in the convict cichlid ( Cichlasoma nigrofasciatum )  

Microsoft Academic Search

Morphine sulfate (5 mg\\/l and 10 mg\\/l) significantly decreased the amount of territorial aggression in the convict cichlid (Cichlasoma nigrofasciatum). The same doses had no effect on predatory aggression (ingestion of brine shrimp). The data suggest that previously demonstrated morphine receptor in the fish has functional properties.

Harry H. Avis; Harman V. S. Peeke

1975-01-01

372

Morphine-related metabolites dierentially activate adenylyl cyclase isozymes after acute and chronic administration  

E-print Network

-glucuronide produces stronger analgesia than morphine, we investigated the effects of acute and chronic by acute and inhibited by chronic treatment. Morphine-3-glucuronide had no effect. The weak opiate agonists codeine and dihydrocodeine are also addictive. These opiates, in contrast to their 3-O

Vogel, Zvi

373

Intrathecal Morphine Attenuates Recovery of Function after a Spinal Cord Injury  

PubMed Central

Abstract Prior work has shown that a high dose (20?mg/kg) of systemic morphine, required to produce significant analgesia in the acute phase of a contusion injury, undermines the long-term health of treated subjects and increases lesion size. Moreover, a single dose of systemic morphine in the early stage of injury (24?h post-injury) led to symptoms of neuropathic pain 3 weeks later, in the chronic phase. The present study examines the locus of the effects using intrathecal morphine administration. Subjects were treated with one of three doses (0, 30, or 90??g) of intrathecal morphine 24?h after a moderate contusion injury. The 90-?g dose produced significant analgesia when subjects were exposed to noxious stimuli (thermal and incremented shock) below the level of injury. Yet, despite analgesic efficacy, intrathecal morphine significantly attenuated the recovery of locomotor function and increased lesion size rostral to the injury site. A single dose of 30 or 90??g of intrathecal morphine also decreased weight gain, and more than doubled the incidence of mortality and autophagia when compared to vehicle-treated controls. Morphine is one of the most effective pharmacological agents for the treatment of neuropathic pain and, therefore, is indispensable for the spinally injured. Treatment can, however, adversely affect the recovery process. A morphine-induced attenuation of recovery may result from increases in immune cell activation and, subsequently, pro-inflammatory cytokine concentrations in the contused spinal cord. PMID:19388818

Moreno, Georgina; Woller, Sarah; Puga, Denise; Hoy, Kevin; Balden, Robyn; Grau, James W.

2009-01-01

374

Morphine modulation of pain processing in medial and lateral pain pathways  

Microsoft Academic Search

BACKGROUND: Despite the wide-spread use of morphine and related opioid agonists in clinic and their powerful analgesic effects, our understanding of the neural mechanisms underlying opioid analgesia at supraspinal levels is quite limited. The present study was designed to investigate the modulative effect of morphine on nociceptive processing in the medial and lateral pain pathways using a multiple single-unit recording

Jin-Yan Wang; Jin Huang; Jing-Yu Chang; Donald J Woodward; Fei Luo

2009-01-01

375

Stereospecific effects of morphine on plasma opioid peptide levels and nociception in dogs  

SciTech Connect

..beta..-endorphin, (met)enkephalin, and (leu)enkephalin were quantitated in canine plasma by radioimmunoassay (RIA) after extraction of the peptides on Sep Pak C18 cartridges. Plasma samples were taken one hour after a 10 mg/kg s.c. injection of (-)-morphine SO/sub 4/ or (+)-morphine HBr. Antinociception, measured by a dog tail-flick test, and morphine-induced emesis, salivation, diarrhea, and ataxia were quantitated before sampling. Control levels for each dog were taken one week earlier at the same time of day after saline injections. Antinociception, morphine signs, and opioid peptide levels in plasma were significantly increased by (-)-morphine. Antinociception increased from zero to 83.54 +/- 11.0%. The number of morphine signs increased from zero to 2.9 +/- 0.28 per dog. ..beta..-endorphin levels increased from 44.52 +/- 4.25 to 90.6 +/- 7.38 pg/ml; (met)enkephalin levels increased from 253.56 +/- 22.04 to 497.1 +/- 58.12 pg/ml; (leu)-enkephalin increased from 141.65 +/- 12.9 to 313.24 +/- 35.95 pg/ml. None of these effects were observed in the dogs that received (+)-morphine. The conclude that morphine stereospecifically inhibits nociception, induces observable signs, and increases plasma opioid peptide levels in dogs.

Adams, M.L.; Morris, D.L.; Dewey, W.L.

1986-03-05

376

Generalization of morphine and lysergic acid diethylamide (LSD) stimulus properties to narcotic analgesics  

Microsoft Academic Search

The present investigation sought to determine whether the stimulus properties of morphine and lysergic acid diethylamide (LSD) would generalize to several narcotic analgesics which vary in their subjective effects. Morphine and saline served as discriminative stimuli for one group of rats in a 2-lever discrimination task. LSD and saline were discriminative stimuli for a second group. Depression of one lever

I. D. Hirschhorn; J. A. Rosecrans

1976-01-01

377

Role of Medial Prefrontal Cortex Narp in the Extinction of Morphine Conditioned Place Preference  

ERIC Educational Resources Information Center

Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus…

Blouin, Ashley M.; Han, Sungho; Pearce, Anne M.; Cheng, KaiLun; Lee, JongAh J.; Johnson, Alexander W.; Wang, Chuansong; During, Matthew J.; Holland, Peter C.; Shaham, Yavin; Baraban, Jay M.; Reti, Irving M.

2013-01-01

378

Effects of acute and chronic morphine on delay discounting in pigeons.  

PubMed

When reinforcers of different magnitudes are concurrently available, choice is greater for a large reinforcer; that choice can be reduced by delaying its delivery, a phenomenon called delay discounting and represented graphically by a delay curve in which choice is plotted as a function of delay to the large reinforcer. Morphine, administered acutely, can alter responding for large, delayed reinforcers. In this study, the impact of morphine tolerance, dependence and withdrawal on choice of delayed reinforcers was examined in six pigeons responding to receive a small amount of food delivered immediately or a larger amount delivered immediately or after delays that increased within sessions. Acutely, morphine decreased responding for the large reinforcer, and the effect was greater when morphine was administered immediately, rather than 6 hr, before sessions. During 8 weeks of daily administration, morphine produced differential effects across pigeons, shifting the delay curve downward in some and upward in others. In all pigeons, tolerance developed to the response-rate-decreasing effects of morphine but not to its effects on delay discounting. When chronic morphine treatment was discontinued, rate of responding decreased in four pigeons, indicating the emergence of withdrawal; choice of the large reinforcer increased, regardless of delay, in all pigeons, an effect that persisted for weeks. These data suggest that chronic morphine administration has long-lasting effects on choice behavior, which might impact vulnerability to relapse in opioid abusers. PMID:23553726

Eppolito, Amy K; France, Charles P; Gerak, Lisa R

2013-05-01

379

Role of hippocampal CA1 area gap junction channels on morphine state-dependent learning.  

PubMed

Morphine produces a state dependent learning. The hippocampus is involved in this kind of learning. Gap junctions (GJs) are involved in some of the effects of morphine and exist in different areas of the hippocampus. We investigated the effects of blocking GJ channels of the hippocampal CA1 area, by means of pre-test bilateral injection of carbenoxolone (CBX), on morphine state dependent learning, using a passive avoidance task. Post-training subcutaneous administrations of morphine (0.5, 2.5, 5 and 7.5mg/kg) dose-dependently impaired memory retrieval. Pre-test administration of morphine (0.5, 2.5, 5 and 7.5mg/kg) induced a state-dependent retrieval of the memory acquired under post-training morphine influence. Pre-test injections of CBX (25, 75 and 150nM) dose dependently prevented memory retrieval by post-training (7.5mg/kg) and pre-test (0.5, 2.5, 5, 7.5mg/kg) injections of morphine. The results suggest that intercellular coupling via GJ channels of the hippocampal CA1 area modulates morphine state dependent learning. PMID:25446430

Beheshti, Siamak; Hosseini, Seyyed Akbar Mir Seyyed; Noorbakhshnia, Maryam; Eivani, Mehdi

2014-12-15

380

The development of tolerance to intrathecal morphine in rat models of visceral and cutaneous pain.  

PubMed

The development of tolerance to intrathecal morphine was studied in rats chronically implanted with intrathecal catheters connected to osmotic minipumps. Measures of cutaneous nociception were the hot plate (HP) and tail flick (TF) tests. Measures of visceral nociception were visceromotor (VM) responses to ramped colorectal distension (CRD) and cardiovascular (CV) responses to phasic colorectal distension. Tolerance to a continuous infusion of 6 or 20 nmol/h of morphine sulfate developed over 6 days. A significant reduction in the dose-dependent effects of intrathecal morphine in the TF and HP tests and VM and CV responses to CRD occurred in rats receiving continuous infusions of morphine. The development of tolerance to intrathecal morphine was similar in both cutaneous and visceral models. PMID:9665657

Ness, T J; Follett, K A

1998-05-22

381

Morphine self-administration in the rat during adjuvant-induced arthritis.  

PubMed

Rats injected with Freund's adjuvant develop a syndrome resembling human rheumatoid arthritis complete with paw swelling, edema and persistent pain. At the onset of pain, arthritic rats and their pain-free littermate controls (vehicle injection) were allowed to self-administer intravenous morphine (5.0 mg/kg/injection) in a 24 hr/day schedule. Self-injected morphine appeared to provide analgesia in arthritic rats as demonstrated by a decreased sensitivity to applied tail pressure. Arthritic rats self-inject significantly less morphine than pain-free animals. Injection of indomethacin, which alleviates the pain and inflammation of the adjuvant-induced disease, reduces, at least initially, morphine self-injection in the arthritic but not pain-free animals. As the adjuvant-induced inflammation and pain dissipated, arthritic rats rapidly began to increase opioid intake. The presence of persistent pain apparently reduces the addictive properties of morphine. PMID:2601574

Lyness, W H; Smith, F L; Heavner, J E; Iacono, C U; Garvin, R D

1989-01-01

382

Brain cholinergic involvement during the rapid development of tolerance to morphine  

NASA Technical Reports Server (NTRS)

The effect of repeated administration of morphine on the activities of the cholinergic enzymes, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), in specific brain regions were studied in rats treated with 10 mg/kg morphine for one or two days. Repeated administration of morphine was associated with a decline in the degree of analgesia produced and with a significant increase of AChE activity of the medulla oblongata. A single injection of morphine resulted in a significant decline in ChAT activity in the hypothalamus, cerebellum, and medulla oblongata regions. After two consecutive injections, no decline in ChAT was observed in these regions, while in the cerebral cortex the second administration elicited a significant decline. The results suggest that the development of tolerance to morphine may be mediated through changes in ChAT activity and lend support to the involvement of the central cholinergic system in narcotic tolerance.

Wahba, Z. Z.; Oriaku, E. T.; Soliman, S. F. A.

1987-01-01

383

Chronic morphine reduces pain-related disability in a rodent model of chronic, inflammatory pain.  

PubMed

Chronic pain is disabling, and the adverse effects of morphine are also disabling. The best way to assess the beneficial effects relative to the potential adverse effects of chronic morphine may be through the use of quantitative measures of functional disability in people and animals experiencing pain. If chronic morphine alleviates chronic pain and its beneficial analgesic effects outweigh whatever adverse effects it may produce, then it should reduce pain-related disability. Rats with adjuvant-induced arthritis were implanted with subcutaneous morphine pellets. Continuous morphine reduced pain-related disability in tasks motivated by food reward or shock avoidance throughout the 35 days of continuous administration--first, in tests that primarily assessed the function of the less severely affected forelimbs, and later, as the inflammation subsided, in tests more dependent on the function of the more severely affected hind limbs. PMID:10472506

Lindner, M D; Plone, M A; Francis, J M; Cain, C K

1999-08-01

384

Changes in key constituents of clonally propagated Artemisia annua L. during preparation of compressed leaf tablets for possible therapeutic use.  

PubMed

Artemisia annua L., long used as a tea infusion in traditional Chinese medicine, produces artemisinin. Although artemisinin is currently used as artemisinin-based combination therapy (ACT) against malaria, oral consumption of dried leaves from the plant showed efficacy and will be less costly than ACT. Many compounds in the plant have some antimalarial activity. Unknown, however, is how these plant components change as leaves are processed into tablets for oral consumption. Here we compared extracts from fresh and dried leaf biomass with compressed leaf tablets of A. annua. Using GC-MS, nineteen endogenous compounds, including artemisinin and several of its pathway metabolites, nine flavonoids, three monoterpenes, a coumarin, and two phenolic acids, were identified and quantified from solvent extracts to determine how levels of these compounds changed during processing. Results showed that compared to dried leaves, artemisinin, arteannuin B, artemisinic acid, chlorogenic acid, scopoletin, chrysoplenetin, and quercetin increased or remained stable with powdering and compression into tablets. Dihydroartemisinic acid, monoterpenes, and chrysoplenol-D decreased with tablet formation. Five target compounds were not detectable in any of the extracts of this cultivar. In contrast to the individually measured aglycone flavonoids, using the AlCl3 method, total flavonoids increased nearly fivefold during the tablet formation. To our knowledge this is the first study documenting changes that occurred in processing dried leaves of A. annua into tablets. These results will improve our understanding of the potential use of not only this medicinal herb, but also others to afford better quality control of intact plant material for therapeutic use. PMID:25228784

Weathers, Pamela J; Towler, Melissa J

2014-12-01

385

Effect of two hydrophobic polymers on the release of gliclazide from their matrix tablets.  

PubMed

Gliclazide is an oral hypoglycemic agent, indicated in non insulin dependent diabetes mellitus and in patients with diabetic retinopathy. It has good tolerability and is a short acting sulfonyl urea that requires large dose to maintain the blood glucose level. So development of a sustained release formulation of gliclazide (GLZ) is required for better patient compliance. This study was conducted to assess the effects of different drug polymer ratios on the release profile of gliclazide from the matrix. Oral matrix tablets of gliclazide were prepared by hot melt method, using pure and blended mixture of glyceryl monostearate (GMS) and stearic acid (SA) in different ratios. In vitro release pattern was studied for 8 h in phosphate buffer media (pH 7.4). Different kinetic models including zero order, first order, Higuchi and Peppas were applied to evaluate drug release behavior. Drug excipient compatibility was evaluated by scanning with DSC and FTIR. Higuchi model was found the most appropriate model for describing the release profile of GLZ and non-Fickian release was found predominant mechanism of drug release. The release of drug from the matrix was greatly controlled by GMS while SA appeared to facilitate the release of drug from matrix tablets. FTIR results showed no chemical interaction between drug and the polymers, and DSC results indicated amorphous state of GLZ and polymers without significant complex formation. The results indicate that matrix tablets of gliclazide using glyceryl monostearate and stearic acid showed marked sustained release properties. PMID:23923399

Hussain, Talib; Saeed, Tariq; Mumtaz, Ahmad M; Javaid, Zeeshan; Abbas, Khizar; Awais, Azeema; Idrees, Hafiz Arfat

2013-01-01

386

Morphine inhibits Purkinje cell survival and dendritic differentiation in organotypic cultures of the mouse cerebellum  

PubMed Central

The effects of morphine on the morphogenesis and survival of calbindin-D28kimmunoreactive Purkinje cells was studied in organotypic explant cultures isolated from 1- or 7-day-old mouse cerebella. To reduce experimental variability, bilaterally matched pairs of organotypic cultures were used to compare the effects of opiate drug treatment. One explant within each pair was untreated, while the remaining explant was continuously treated for 7 to 10 days with morphine, morphine plus naloxone, or naloxone alone. In explants derived from 1-day-old mice, morphine treatment significantly reduced Purkinje cell dendritic length compared to symmetrically-matched untreated control explants. The concentration of morphine estimated to cause a half-maximal reduction (EC50) in dendritic length was 4.9 × 10?8 M. At higher concentrations (EC50 = 3.6 × 10?6 M), morphine also significantly decreased the number of Purkinje cells in explants from 1-day-old mice compared to untreated explants. Electron microscopy identified increased numbers of degenerating Purkinje cells in explants derived from 1-day-old mice. This showed that high concentrations (10?5 M) of morphine reduced Purkinje cell numbers by decreasing their rate of survival. In explants derived from 7-day-old mice, morphine (10?5 M) neither affected Purkinje cell dendritic length nor cell numbers compared to symmetrically-matched untreated (control) explants. Collectively, these findings suggest that morphine per se, through a direct action on the cerebellum, can affect Purkinje cell differentiation and survival. The results additionally suggest there is a critical period during development when Purkinje cells are especially vulnerable to the effects of morphine. PMID:7821399

Hauser, Kurt F.; Gurwell, Julie A.; Turbek, Carol S.

2015-01-01

387

Photoaffinity labeling of rat liver microsomal morphine UDP-glucuronosyltransferase by ( sup 3 H)flunitrazepam  

SciTech Connect

Benzodiazepines have been shown to competitively inhibit morphine glucuronidation in rat and human hepatic microsomes. Flunitrazepam exerted a potent competitive inhibition of rat hepatic morphine UDP-glucuronosyltransferase (UDPGT) activity (Ki = 130 microM). It has no effect on the activity of p-nitrophenol, 17 beta-hydroxysteroid, 3 alpha-hydroxysteroid, or 4-hydroxybiphenyl UDPGTs. Because flunitrazepam is an effective photoaffinity label for benzodiazepine receptors, studied were performed in solubilized rat hepatic microsomes and with partially purified preparations of morphine UDPGT to determine the enhancement of flunitrazepam inhibition and binding to morphine UDPGT promoted by exposure to UV light. Under UV light, flunitrazepam inhibition was markedly enhanced. UV light exposure also led to a marked increase in binding of (3H)flunitrazepam to microsomal protein, which was protected substantially by preincubation with morphine. Testosterone, androsterone, and UDP-glucuronic acid did not protect against UV-enhanced flunitrazepam binding, and morphine did not reverse flunitrazepam binding once binding had occurred. As morphine UDPGT was purified, a good correlation was found between the increases in specific activity of morphine UDPGT and flunitrazepam binding to protein. Chromatofocusing chromatography showed that flunitrazepam bound only to fractions containing active morphine UDPGT, and no binding to 4-hydroxybiphenyl UDPGT was observed. Fluorography of a sodium dodecyl sulfate-polyacrylamide electrophoresis gel of solubilized hepatic microsomes that had been treated with (3H) flunitrazepam under UV light revealed a band with a monomeric molecular weight between 54,000 and 58,000. This monomeric molecular weight compares favorably with the reported monomeric molecular weight of homogeneous morphine UDPGT (56,000).

Thomassin, J.; Tephly, T.R. (Univ. of Iowa, Iowa City (USA))

1990-09-01

388

The effect of vitamin C on morphine self-administration in rats  

PubMed Central

Background: Recent studies have shown that addiction may be caused by abnormality of neurotransmission in the brain. Two neurotransmitters that involve into morphine addiction are dopamine and glutamate. The glutamatergic and dopaminergic systems are also involved in morphine tolerance and morphine withdrawal syndrome signs. Ascorbic acid (AA), as the antioxidant releases from the glutamatergic neurons, modulates the action of the dopamine and glutamate systems. In this study, the effect of AA on morphine self-administration and morphine withdrawal symptoms has been investigated. Materials and Methods: Male Wistar rats (250 - 300g) were anesthetized with ketamine (11%) and xailazine (15%). The cannula was inserted into the right jugular vein, and it was fixed subcutaneously on the skull. After surgery the animals were placed in individual home cages, and they were allowed to recover from the operation for five days, before the test. The animals were subjected to self-administration morphine for12 consecutive days, two-hour/sessions. The number of infusions and number of active and passive lever pressings were recorded. Results: An intra peritoneal injection of Ascorbic acid (AA) (400 mg/kg, i.p.), 30 minutes before morphine self-administration, produced a significant decrease in 12 days self-administration of morphine and withdrawal syndrome signs (P < 0.05). The morphine withdrawal signs (MWS) were recorded after naloxone precipitation, which decreased significantly with the injection of AA (400,700mg/kg), (<0.05). The number of self-infusions and the number of active lever pressings had significantly decreased after AA injection (P < 0.05). Conclusion: The chronic administration of AA may prevent the development of tolerance and physical dependence on morphine self-administration via the glutamatergic system. PMID:25250292

Talkhooncheh, Mahboobeh; Alaei, Hojjat Allah; Ramshini, Effat; Shahidani, Somaei

2014-01-01

389

Morphine-induced nitric oxide production in isolated, iris-ciliary bodies  

PubMed Central

Considerable evidence suggests that the nitric oxide (NO)/cGMP signaling pathway plays an integral role in opioid receptor-mediated responses in the cardiovascular and immune systems. Previous studies in our laboratory and others have shown that nitric oxide (NO) plays a role in morphine-induced reduction of intraocular pressure (IOP) and pupil diameter (PD) in the New Zealand white (NZW) rabbit. The present study is designed to determine the effect of morphine on NO production in the isolated, iris-ciliary body (ICB), site of aqueous humor production, as this effect could be associated with morphine-stimulated changes in aqueous humor dynamics and iris function. ICBs obtained from normal NZW rabbits were utilized in these experiments. In some experiments, ICB samples were treated with morphine (1, 10 and 100 ?M) for 1 hour and later examined for changes in NO levels using a NO detection kit. In other experiments, tissue samples were pretreated with naloxone (non-selective opioid receptor antagonist), L-NAME (non-selective NO synthase inhibitor) or GSH (sulfhydryl reagent) for 30 minutes, followed by treatment with morphine (10 ?M). Morphine caused a concentration-dependent increase in the release of NO from ICBs. Levels of NO detected in the incubation medium of ICB samples increased from 1.49 ± 0.19 (control) to 8.81 ± 2.20 ?M/mg protein (morphine treated; 100 ?M). Morphine-stimulated release of NO was significantly inhibited in tissues pretreated with 10 ?M naloxone, L-NAME, or GSH. Results obtained from this study suggest that morphine stimulates NO release from the ICB through a mechanism that involves activation of NO-releasing opioid receptors. These results support the in vivo effects of morphine demonstrated in previous studies. PMID:19555685

Dortch-Carnes, Juanita; Randall, Karen Russell

2009-01-01

390

Morphine dependence in single enteric neurons from the mouse colon requires deletion of ??arrestin2  

PubMed Central

Abstract Chronic administration of morphine results in the development of tolerance to the analgesic effects and to inhibition of upper gastrointestinal motility but not to colonic motility, resulting in persistent constipation. In this study we examined the effect of chronic morphine in myenteric neurons from the adult mouse colon. Similar to the ileum, distinct neuronal populations exhibiting afterhyperpolarization (AHP)?positive and AHP?negative neurons were identified in the colon. Acute morphine (3 ?M) decreased the number of action potentials, and increased the threshold for action potential generation indicative of reduced excitability in AHP?positive neurons. In neurons from the ileum of mice that were rendered antinociceptive tolerant by morphine?pellet implantation for 5 days, the opioid antagonist naloxone precipitated withdrawal as evidenced by increased neuronal excitability. Overnight incubation of ileum neurons with morphine also resulted in enhanced excitability to naloxone. Colonic neurons exposed to long?term morphine, remained unresponsive to naloxone suggesting that precipitated withdrawal does not occur in colonic neurons. However, morphine?treated colonic neurons from ??arrestin2 knockout mice demonstrated increased excitability upon treatment with naloxone as assessed by change in rheobase, number of action potentials and input resistance. These data suggest that similar to the ileum, acute exposure to morphine in colonic neurons results in reduced excitability due to inhibition of sodium currents. However, unlike the ileum, dependence to chronic exposure of morphine develops in colonic neurons from the ??arrestin2 knockout mice. These studies corroborate the in?vivo findings of the differential role of neuronal ??arrestin2 in the development of morphine tolerance/dependence in the ileum and colon. PMID:25194025

Smith, Tricia H.; Ngwainmbi, Joy; Hashimoto, Atsushi; Dewey, William L.; Akbarali, Hamid I.

2014-01-01

391

Orphanin FQ/nociceptin attenuates the development of morphine tolerance in rats  

PubMed Central

Recent evidence from studies in mice lacking the opioid receptor-like (ORL-1) receptor and from experiments using antibodies raised against orphanin FQ/nociceptin (OFQ/N) suggest that this peptide may be involved in morphine tolerance. In the present study we sought to investigate if administration of exogenous OFQ/N would modulate the development of tolerance to the antinociceptive effect of morphine. Rats were treated for 3 days with either saline or morphine (10?mg?kg?1, s.c.) followed, 15 and 75?min later, by two intracerebroventricular injections of either artificial cerebrospinal fluid (aCSF) or OFQ/N. The dose of OFQ/N was doubled each day (7.5, 15, 30?nmol). On day 4, rats were tested on a hot plate apparatus before and 30, 60 and 90?min after morphine administration. Repeated OFQ/N treatment did not affect basal nociceptive responses or morphine-induced antinociception. However, the same treatment significantly attenuated the development of morphine tolerance. Since learning and memory could contribute to the development of morphine tolerance, in subsequent studies, we examined the effect of OFQ/N administered in the CA3 region of the hippocampus, where OFQ/N has been shown to block LTP and impair spatial memory. A greater attenuation of morphine tolerance with no alteration of baseline hot plate latency or morphine-induced antinociception was observed when OFQ/N was administered in this area of the rat brain. Taken together, our results demonstrate that OFQ/N may act in the hippocampus to attenuate morphine tolerance. PMID:11588106

Lutfy, Kabirullah; Hossain, Syed M; Khaliq, Imran; Maidment, Nigel T

2001-01-01

392

Patient-controlled analgesia in the pediatric population: morphine versus hydromorphone  

PubMed Central

Objective Patient controlled analgesia (PCA) is commonly used to provide analgesia following surgical procedures in the pediatric population. Morphine and hydromorphone remain the most commonly used opioids for PCA. Although both are effective, adverse effects may occur. When these adverse effects are unremitting or severe, opioid rotation may be required. In this study, we retrospectively evaluated PCA use, the adverse effect profile, and the frequency of opioid rotation. Methods This retrospective study was performed at Nationwide Children’s Hospital (Columbus, OH). The hospital’s electronic registry was queried for PCA use delivering either morphine or hydromorphone from January 1, 2008 to December 31, 2010. Results A total of 514 patients were identified, that met study entry criteria. Of the 514 cases, 298 (56.2%) were initially started on morphine and 225 (43.8%) were initially started on hydromorphone. There were a total of 26 (5.1%) opioid changes in the cohort of 514 patients. Of the 26 switches, 23 of 298 (7.7%) were from morphine to hydromorphone, and 3 of 225 (1.3%) were from hydromorphone to morphine (P=0.0008). Of the 17 morphine-to-hydromorphone switches with adverse effects, pruritus (64.7%), and inadequate pain control (47.1%) were the most common side effects. The most common side effect resulting in a hydromorphone-to-morphine switch was nausea (66.7%). Conclusion PCA switches from morphine-to-hydromorphone (88.5%) were more common than vice-versa (11.5%). The most common reasons for morphine-to-hydromorphone switch were pruritus and inadequate pain control. These data suggest that a prospective study is necessary to determine the side effect differences between morphine and hydromorphone in pediatric PCA. PMID:25152630

DiGiusto, Matthew; Bhalla, Tarun; Martin, David; Foerschler, Derek; Jones, Megan J; Tobias, Joseph D

2014-01-01

393

Glial activation and midkine and pleiotrophin transcription in the ventral tegmental area are modulated by morphine administration.  

PubMed

Opiates cause persistent restructuring in the mesolimbic reward system. Although a possible role for midkine and pleiotrophin cytokines in the field of synaptic plasticity has been proposed, it has not been assessed whether morphine administration regulates astrogliosis and midkine and pleiotrophin transcription. We observed that single morphine injection and chronic morphine increased glial fibrillary acidic protein expression in the ventral tegmental area (VTA). Interestingly, single morphine injection and chronic morphine increased VTA midkine and pleiotrophin mRNA expression. Given these results, we hypothesize a role for these cytokines in mediating, at least in part, acute neuroprotective effects and chronic neurotrophic adaptations that contribute to drug dependence. PMID:25108770

García-Pérez, Daniel; Luisa Laorden, M; Núñez, Cristina; Victoria Milanés, M

2014-09-15

394

Indirect Competitive Assays on DVD for Direct Multiplex Detection of Drugs of Abuse in Oral Fluids.  

PubMed

On-site oral fluid testing for drugs of abuse has become prominent in order to take immediate administrative action in an enforcement process. Herein, we report a DVD technology-based indirect competitive immunoassay platform for the quantitative detection of drugs of abuse. A microfluidic approach was adapted to prepare multiplex immunoassays on a standard DVD-R, an unmodified multimode DVD/Blu-Ray drive to read signal, and a free disc-quality analysis software program to process the data. The DVD assay platform was successfully demonstrated for the simultaneous, quantitative detection of drug candidates (morphine and cocaine) in oral fluids with high selectivity. The detection limit achieved was as low as 1.0 ppb for morphine and 5.0 ppb for cocaine, comparable with that of standard mass spectrometry and ELISA methods. PMID:25540088

Zhang, Lingling; Li, Xiaochun; Li, Yunchao; Shi, Xiaoli; Yu, Hua-Zhong

2015-02-01

395

Long-term Morphine-treated Rats are more Sensitive to Antinociceptive Effect of Diclofenac than the Morphine-naive rats  

PubMed Central

This study investigates the effectiveness of the antinociceptive effects of diclofenac, an NSAID, on the nociceptive behavior of morphine-treated rats on formalin test. Rats were treated with morphine-containing drinking water for twenty one days, which induced morphine dependence. The antinociceptive effects of 8, 16, and 32 mg/kg doses of diclofenac were then evaluated and compared with distilled water in a formalin-based model of pain. Diclofenac potentiated pain suppression in morphine-dependent rats during the interphase of the formalin test and reduced the pain score during phase II. The post-test analysis revealed that both 16 mg/kg (p < 0.0001) and 32 mg/kg (p < 0.0001) doses of diclofenac had a significant effect on the interphase, while 8 mg/kg (p < 0.05), 16 mg/kg (p < 0.05), and 32 mg/kg (p < 0.01) doses of diclofenac significantly affected phase II. In contrast, the antinociceptive effects of diclofenac on morphine-naïve rats were observed during phase II only with the a 32 mg/kg dose (p < 0.05). In general, these results suggest that the long-term use of morphine in rats increases their sensitivity to the antinociceptive effects of diclofenac. Furthermore, the results support the existence of a non-opioid-dependent mechanism of pain suppression during the interphase of formalin test. PMID:24250586

Akbari, Esmaeil; Mirzaei, Ebrahim; Shahabi Majd, Naghi

2013-01-01

396

Pharmaceutical tablet compaction : product and process design  

E-print Network

This thesis explores how tablet performance is affected by microstructure, and how microstructure can be controlled by selection of excipients and compaction parameters. A systematic strategy for formulation and process ...

Pore, Mridula

2009-01-01

397

Neurochemical effects of benzodiazepine and morphine on freshwater mussels.  

PubMed

The purpose of this study was to examine the neurochemical effects of morphine, diazepam, a common benzodiazepine, and an effluent concentrate on the endemic freshwater mussel Elliptio complanata. Mussels were exposed to the drugs and to the solid-phase concentrate of a municipal effluent and left to stand at 15 degrees C for 48h. Neurochemical effects were determined by monitoring changes in dopamine, serotonin, glutamate and gamma-aminobutyric acid (GABA) levels in the visceral mass (containing the nerve ganglia) of mussels. The activities of acetylcholinesterase (AChE), dopamine and serotonin-dependent adenylyl cyclase (ADC) were also determined in the mussels. Oxidative stress was determined by tracking changes in lipid peroxidation (LPO) in the mitochondrial and post-mitochondrial fractions. The results revealed that the drugs and the effluent extract were biologically active in mussels. Morphine reduced serotonin and increased dopamine in mussel tissues while reducing AChE activity and increasing GABA levels. This suggests the induction of a relaxation state in mussels. Diazepam also reduced serotonin levels but produced no change in dopamine levels. However, dopamine-sensitive ADC activity was readily activated, indicating the potential effect on opiate signaling. Diazepam increased glutamate levels slightly, but AChE remained stable. The increase in both dopamine ADC activity and glutamate concentrations was also associated with greater oxidative stress on the mitochondrial and post-mitochondrial fractions in cells. A comparison of the global response pattern of these drugs with those of the effluent extract revealed only a relative proximity to morphine. In conclusion, the data warrant more studies on the analysis of opiates and benzodiazepines in municipal effluents to better address the potential environmental hazard of these neuroactive drug classes to aquatic organisms. PMID:20398796

Gagné, F; André, C; Gélinas, M

2010-08-01

398

A randomized, crossover design study of sevelamer carbonate powder and sevelamer hydrochloride tablets in chronic kidney disease patients on haemodialysis  

PubMed Central

Background. Sevelamer carbonate is an improved, buffered form of sevelamer hydrochloride developed for the treatment of hyperphosphataemia in CKD patients. Sevelamer carbonate formulated as a powder for oral suspension presents a novel, patient-friendly alternative to tablet phosphate binders. This study compared the safety and efficacy of sevelamer carbonate powder with sevelamer hydrochloride tablets in CKD patients on haemodialysis. Methods. This was a multi-centre, open-label, randomized, crossover design study. Thirty-one haemodialysis patients were randomly assigned to either sevelamer carbonate powder or sevelamer hydrochloride tablets for 4 weeks followed by a crossover to the other regimen for an additional 4 weeks. Results. The mean serum phosphorus was 1.6 ± 0.5 mmol/L (5.0 ± 1.5 mg/dL) during sevelamer carbonate powder treatment and 1.7 ± 0.4 mmol/L (5.2 ± 1.1 mg/dL) during sevelamer hydrochloride tablet treatment. Sevelamer carbonate powder and sevelamer hydrochloride tablets are equivalent in controlling serum phosphorus; the geometric least square mean ratio was 0.95 (90% CI 0.87–1.03). No statistically significant or clinically meaningful differences were observed in calcium × phosphorus product and lipid levels between sevelamer carbonate powder and sevelamer hydrochloride tablets. Serum bicarbonate levels increased 2.7 ± 3.7 mmol/L (2.7 ± 3.7 mEq/L) during sevelamer carbonate treatment. No statistically significant change in bicarbonate was observed during sevelamer hydrochloride treatment. Sevelamer carbonate powder and sevelamer hydrochloride were well tolerated during this study. Conclusions. Sevelamer carbonate powder and sevelamer hydrochloride tablets are equivalent in controlling serum phosphorus and well tolerated in CKD patients on haemodialysis. Bicarbonate levels improved only during sevelamer carbonate treatment. Sevelamer carbonate powder should provide a welcomed new option for the treatment of hyperphosphataemia for CKD patients on dialysis. PMID:19666658

Fan, Stanley; Ross, Calum; Mitra, Sandip; Kalra, Philip; Heaton, Jeremy; Hunter, John; Plone, Melissa; Pritchard, Nick

2009-01-01

399

Tablets for Timely Design Documentation  

NSDL National Science Digital Library

One of the biggest challenges we have experienced in supervising digital systems senior design projects is the quality and completeness of the individual lab notebooks. Of the five outcomes we continuously track for this capstone course, the lab notebooks have consistently received the lowest quantitative scores. A significant improvement was achieved three years ago when we transitioned from carbon paper and pen notebooks to on-line (HTML) notebooks. Many teams took advantage of (and put to good use) the ability to post digital pictures of prototyping setups, provide hyperlinks to all their device datasheets, post their latest schematics and software listings for evaluation, and post video clips of their project in action (as verification of their project success criteria). The primary drawback has been the need for students to be in front of a networked computer to make lab notebook entries; consequently, the notebook updates still tended to be done in spurts (typically after the fact) rather than in real time. Project work (and inspiration), in fact, does not always occur in a lab setting, where networked computers are readily available, nor does it occur when all team members are working in the same physical location. Our hypothesis is that equipping each project team with wireless Tablet PCs should not only significantly improve the spontaneity (and regularity) with which the on-line lab notebooks are updated, but also facilitate collaboration among team members working on the design project at different locations. An HP Technology for Teaching Grant has provided a critical mass of Tablet PCs to test this hypothesis. A description of how the equipment provided is being utilized, along with a discussion of the preliminary results obtained, is presented in this paper.

Brown, Cordelia; Johnson, Mark; Meyer, David

2009-08-25

400

Development and characterization of buccoadhesive nifedipine tablets  

Microsoft Academic Search

The buccoadhesive controlled-release tablets for delivery of nifedipine were prepared by direct compression of carboxymethyl cellulose (CMC) with carbomer (CP), which showed superior bioadhesion properties compared to polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), hydroxypropylmethyl cellulose (HPMC), and acacia in a modified tensiometry method in vitro. The tablets containing 30mg of nifedipine and various amounts of CMC and CP showed a zero-order

J. Varshosaz; Z. Dehghan

2002-01-01

401

Preparation and evaluation of once-daily sustained-release coated tablets of tolterodine-L-tartrate.  

PubMed

In this study, once-daily, sustained-release matrix tablets of tolterodine l-tartrate (TOL) for treatment of overactive bladder (OAB) were prepared by direct compression using various amounts of hydrophilic polymers such as HPMC 2910 and HPMC 2208 along with other tablet excipients; the tablets were then coated. In vitro dissolution studies were carried out under different pH conditions. The dissolution data were fitted into zero-order, first-order, Higuchi and Korsemeyer-Peppas models to identify the pharmacokinetics and mechanism of drug release. Among the four formulations (F1-F4), the dissolution profiles of formulation F2 were most similar to the marketed product with similarity and difference factors of 70.25 and 1.59 respectively. Furthermore, pharmacokinetic studies were carried out in healthy human volunteers after oral administration of the prepared TOL sustained-release matrix-coated tablet and the marketed product. The results revealed that the pharmacokinetic parameters of AUC, Cmax, Tmax, t1/2, Kel, and MRT of TOL for the developed formulation (F2) were not significantly different from that for the marketed product, suggesting that they were bioequivalent. Therefore, the developed sustained-release tablet formulation of TOL could be an alternative dosage form to the SR capsule for treatment of OAB. PMID:24184032

Pradhan, Roshan; Kim, Yong-Il; Chang, Sun Woo; Kim, Jong Oh

2014-01-01

402

Gastroretentive Pulsatile Release Tablets of Lercanidipine HCl: Development, Statistical Optimization, and In Vitro and In Vivo Evaluation  

PubMed Central

The present study was aimed at the development of gastroretentive floating pulsatile release tablets (FPRTs) of lercanidipine HCl to enhance the bioavailability and treat early morning surge in blood pressure. Immediate release core tablets containing lercanidipine HCl were prepared and optimized core tablets were compression-coated using buoyant layer containing polyethylene oxide (PEO) WSR coagulant, sodium bicarbonate, and directly compressible lactose. FPRTs were evaluated for various in vitro physicochemical parameters, drug-excipient compatibility, buoyancy, swelling, and release studies. The optimized FPRTs were tested in vivo in New Zealand white rabbits for buoyancy and pharmacokinetics. DoE optimization of data revealed FPRTs containing PEO (20%?w/w) with coat weight 480?mg were promising systems exhibiting good floating behavior and lag time in drug release. Abdominal X-ray imaging of rabbits after oral administration of the tablets, confirmed the floating behavior and lag time. A quadratic model was suggested for release at 7th and 12th?h and a linear model was suggested for release lag time. The FPRT formulation improved pharmacokinetic parameters compared to immediate release tablet formulation in terms of extent of absorption in rabbits. As the formulation showed delay in drug release both in vitro and in vivo, nighttime administration could be beneficial to reduce the cardiovascular complications due to early morning surge in blood pressure.

Reddy, Gagganapalli Santhoshi; Nayak, Usha Yogendra; Deshpande, Praful Balavant; Mutalik, Srinivas

2014-01-01

403

Chronic inflammatory pain prevents tolerance to the antinociceptive effect of morphine microinjected into the ventrolateral periaqueductal gray of the rat  

PubMed Central

The ventrolateral periaqueductal gray (vlPAG) contributes to morphine antinociception and tolerance. Chronic inflammatory pain causes changes within the PAG that are expected to enhance morphine tolerance. This hypothesis was tested by assessing antinociception and tolerance following repeated microinjections of morphine into the vlPAG of rats with chronic inflammatory pain. Microinjection of morphine into the vlPAG reversed the allodynia caused by intraplantar administration of Complete Freund's Adjuvant (CFA), and produced antinociception on the hot plate test. Although there was a gradual decrease in morphine antinociception with repeated testing, there was no evidence of tolerance when morphine and saline treated rats with hind paw inflammation were tested with cumulative doses of morphine. In contrast, repeated morphine injections into the vlPAG caused a rightward shift in the morphine dose-response curve in rats without hind paw inflammation, as would be expected with the development of tolerance. The lack of tolerance in CFA treated rats was evident whether rats were exposed to repeated behavioral testing or not (Experiment 2) and whether they were treated with 4 or 8 prior microinjections of morphine into the vlPAG (Experiment 3). These data demonstrate that chronic inflammatory pain does not disrupt the antinociceptive effect of microinjecting morphine into the vlPAG, but it does disrupt the development of tolerance. PMID:24161274

Mehalick, Melissa L.; Ingram, Susan L.; Aicher, Sue; Morgan, Michael M

2013-01-01

404

Formulation and optimization of potassium iodide tablets  

PubMed Central

The use of potassium iodide (KI) as a protective agent against accidental radioactive exposure is well established. In this study, we aimed to prepare a KI tablet formulation using a direct compression method. We utilized Design of Experiment (DoE)/mixture design to define the best formulation with predetermined physical qualities as to its dissolution, hardness, assay, disintegration, and angle of repose. Based on the results from the DoE, the formulation had the following components (%w/w): Avicel 48.70%, silicon dioxide 0.27%, stearic acid (1.00%), magnesium stearate 2.45%, and dicalcium phosphate 18.69%, in addition to potassium iodide 28.89% (130 mg/tablet). This formulation was scaled-up using two tablet presses, a single-punch press and a rotary mini tablet press. The final scaled-up formulation was subjected to a variety of quality control tests, including photo-stability testing. The results indicate that potassium iodide tablets prepared by a rotary mini tablet press had good pharmaceutical characteristics and a shelf-life of 25 days when stored at room temperature protected from light.

Al-Achi, Antoine; Patel, Binit

2014-01-01

405

A new brittleness index for compacted tablets.  

PubMed

A dimensionless index that quantifies the brittle or ductile character of tablets is presented. The work of failure (WOF) of crushed or broken flat tablets is calculated by numerical integration of the force-displacement measurement in a flexure tester. The ratio between WOF and the crushing force (F) corrected for the diameter of the tablet (D) is proposed to express the brittle/ductile index (BDI). [Formula: see text] This dimensionless index quantitatively denotes the brittle/ductile character of the compacted material as the normalized deformation in percentage of a cylindrical tablet at the breaking point. For ideal brittle materials, the BDI value will be 0 and for complete plastic deformation, that is, a total compression of the tablet without fracture, BDI will be 100. The validity and discriminative power is demonstrated on mixtures of microcrystalline cellulose and lactose. The robust measure of brittleness with an acceptable accuracy is obtained with only a minor influence of the tablet diameter and the speed of platen. PMID:24258281

Sonnergaard, Jørn M

2013-12-01

406

Synthesis, characterization and evaluation of methacrylamide grafted gellan as sustained release tablet matrix.  

PubMed

In the present study, the microwave induced synthesis of polymethacrylamide-grafted-gellan gum (PMaa-g-GG) was carried out by free radical initiation using cerric (IV) ammonium nitrate (CAN) as redox initiator. Concentrations of methacrylamide (Maa), CAN and microwave irradiation time were taken as variable synthetic parameters. The modified polysaccharide obtained from different synthetic conditions was then characterized by FTIR, CHN analysis, DSC and powder X-ray diffraction. The yield and extent of grafting were assessed by determining percentage grafting, percentage grafting efficiency, percentage conversion and these were correlated with elemental analysis. The acute oral toxicity study of modified polysaccharide was performed as per OECD guideline. Histological comparison of different organs between control and test animal showed no significant difference. Sustained release tablets of diclofenac sodium (DS) were prepared with modified gellan. In vitro dissolution study showed the tablets were capable of releasing the drug over a period of 8 h. PMID:25316428

Nandi, Gouranga; Patra, Poushali; Priyadarshini, Rosy; Kaity, Santanu; Ghosh, Lakshmi Kanta

2015-01-01

407

Persistent Peripheral Inflammation Attenuates Morphine-induced Periaqueductal Gray Glial Cell Activation and Analgesic Tolerance in the Male Rat  

PubMed Central

Morphine is among the most prevalent analgesics prescribed for chronic pain. However, prolonged morphine treatment results in the development of analgesic tolerance. An abundance of evidence has accumulated indicating that CNS glial cell activity facilitates pain transmission and opposes morphine analgesia. While the midbrain ventrolateral periaqueductal gray (vlPAG) is an important neural substrate mediating pain modulation and the development of morphine tolerance, no studies have directly assessed the role of PAG-glia. Here we test the hypothesis that morphine-induced increases in vlPAG glial cell activity contribute to the development of morphine tolerance. As morphine is primarily consumed for the alleviation of severe pain, the influence of persistent inflammatory pain was also assessed. Administration of morphine, in the absence of persistent inflammatory pain, resulted in the rapid development of morphine tolerance and was accompanied by a significant increase in vlPAG glial activation. In contrast, persistent inflammatory hyperalgesia, induced by intraplantar administration of Complete Freund’s Adjuvant (CFA), significantly attenuated the development of morphine tolerance. No significant differences were noted in vlPAG glial cell activation for CFA-treated animals versus controls. These results indicate that vlPAG glia are modulated by a persistent pain state, and implicate vlPAG glial cells as possible regulators of morphine tolerance. Perspective The development of morphine tolerance represents a significant impediment to its use in the management of chronic pain. We report that morphine tolerance is accompanied by increased glial cell activation within the vlPAG, and that the presence of a persistent pain state prevented vlPAG glial activation and attenuated morphine tolerance. PMID:23395474

Eidson, Lori N.; Murphy, Anne Z.

2014-01-01

408

Gene Expression Profile of Calcium/Calmodulin-Dependent Protein Kinase II? in Rat's Hippocampus during Morphine Withdrawal  

PubMed Central

Introduction Calcium/calmodulin-dependent protein kinase II (CaMKII) which is highly expressed in the hippocampus is known to play a pivotal role in reward-related memories and morphine dependence. Methods In the present study, repeated morphine injections once daily for 7 days was done to induce morphine tolerance in male Wistar rats, after which gene expression profile of ?-isoform of CaMKII (CaMKII?) in the hippocampus was evaluated upon discontinuation of morphine injection over 21 days of morphine withdrawal. Control groups received saline for 7 consecutive days. For gene expression study, rats’ brains were removed and the hippocampus was dissected in separate groups on days 1, 3, 7, 14, and 21 since discontinuation of of morphine injection. A semi-quantitative RT-PCR method was used to evaluate the gene expression profile. Results Tolerance to morphine was verified by a significant decrease in morphine analgesia in a hotplate test on day 8 (one day after the final repeated morphine injections). Results showed that gene expression of CaMKII? at mRNA level on day 1, 3, 7, 14 and 21 of morphine withdrawal was significantly altered as compared to the saline control group. Post hoc Tukey's test revealed a significantly enhanced CaMKII? gene expression on day 14. Discussion It can be concluded that CaMKII? gene expression during repeated injections of morphine is increased and this increase continues up to 14 days of withdrawal then settles at a new set point. Therefore, the strong morphine reward-related memory in morphine abstinent animals may, at least partly be attributed to, the up-regulation of CaMKII? in the hippocampus over 14 days of morphine withdrawal. PMID:25337341

Ahmadi, Shamseddin; Amiri, Shahin; Rafieenia, Fatemeh; Rostamzadeh, Jalal

2013-01-01

409

Randomized controlled trial of sodium phosphate tablets vs polyethylene glycol solution for colonoscopy bowel cleansing  

PubMed Central

AIM: To compare efficacy, patient compliance, acceptability, satisfaction, safety, and adenoma detection rate of sodium phosphate tablets (NaP, CLICOLONTM) to a standard 4 L polyethylene glycol (PEG) solution for bowel cleansing for adults undergoing colonoscopy. METHODS: In this multicenter, randomized, prospective, investigator-blind study, the relatively young (19-60 years) healthy outpatients without comorbidity were randomly assigned to one of two arms. All colonoscopy were scheduled in the morning. The NaP group was asked to take 4 tablets, 5 times the evening before and 4 tablets, 3 times early on the morning of the colonoscopy. The PEG group was asked to ingest 2 L of solution the evening before and 2 L early in the morning of the procedure. Adequacy of bowel preparation was scored using the Boston bowel preparation scale. RESULTS: No significant differences were observed between the NaP group (n = 158) and PEG group (n = 162) in bowel cleansing quality (adequate preparation 93.0% vs 92.6%, P = 0.877), patient compliance (P = 0.228), overall adverse events (63.3% vs 69.1%, P = 0.269), or adenoma detection rate (34.8% vs 35.2%, P = 0.944). Patient acceptability, satisfaction, and patient rating of taste were higher in the NaP group than in the PEG group (P < 0.001). CONCLUSION: NaP tablets, compared with PEG solution, produced equivalent colon cleansing, did not cause more side effects, and had better patient acceptability and satisfaction in the relatively young (age < 60 years) healthy individuals without comorbidity. An oral tablet formulation could make bowel preparation less burdensome, resulting in greater patient participation in screening programs. PMID:25400471

Jung, Yoon Suk; Lee, Chang Kyun; Kim, Hyo Jong; Eun, Chang Soo; Han, Dong Soo; Park, Dong Il

2014-01-01

410

Formulation, development, and performance evaluation of metoclopramide HCl oro-dispersible sustained release tablet.  

PubMed

The present study was undertaken to develop and evaluate an oro-dispersible, sustained release tablet of metoclopramide HCl. The technology was comprised of developing sustained release microparticles, and compression of resultant microspheres into a fast dispersible tablet by direct compression. The microspheres of metoclopramide HCl were prepared by an emulsification-solvent evaporation method using ethylcellulose as the matrix polymer. The prepared microspheres were evaluated for morphology, particle size, entrapment efficiency, and in vitro drug release characteristics. Scanning electron microscopy demonstrated spherical particles with a mean diameter of 81.27 ± 5.87 ?m and the drug encapsulation efficiency was found to be 70.15 ± 3.06%. The process and formulation variables such as rotation speed, polymer concentration, and drug concentration influenced the drug encapsulation efficiency and in vitro drug release. Optimized microspheres were compressed into tablets which were comprised of metoclopramide HCl microspheres, 53% (w/v) of D-mannitol granules, 7% (w/w) of Polyplasdone XL 10, and 0.5% (w/w) of calcium stearate. The tablets demonstrated a hardness of 59 ± 3 N, friability of 0.21% and disintegration time of 27 ± 3 sec. The formulations were subjected to stability studies as per ICH guidelines and were found to be stable after a 6 month study. In vivo experiments conducted in rats demonstrated that a constant level of metoclopramide HCl in plasma could be maintained for up to 20 h at a suitable concentration for antiemetic activity. An appropriate combination of excipients made it possible to obtain orally disintegrating sustained release tablets of metoclopramide HCl using simple and conventional techniques. PMID:22076769

Kasliwal, Nikhil; Negi, Jeetendra Singh; Jugran, Vandana; Jain, Rahul

2011-10-01

411

Enhancement of the contact hypersensitivity reaction by acute morphine administration at the elicitation phase.  

PubMed

The present study investigated the effects of morphine on the irritant contact sensitivity (ICS) and contact hypersensitivity (CHS) reaction. ICS was induced by croton oil application on the pinnae of naïve rats. Morphine injected prior to croton oil application did not affect the ICS response when assessed by measurements of pinnae thickness. CHS was induced by applying the antigen 2,4-dinitro-1-fluorobenzene (DNFB) to the pinnae of rats sensitized to DNFB. Rats received an injection of morphine prior to either initial antigen exposure (sensitization) or antigen reexposure (challenge). Morphine prior to challenge, but not sensitization, resulted in a pronounced enhancement of the CHS response as measured by pinna thickness. Quantitative PCR also showed increased IFN-gamma mRNA levels in the inflamed tissue of morphine-treated rats. Naltrexone blocked the morphine-induced enhancement of the CHS response. The differential effects of morphine suggest that opioids have a more pronounced effect on in vivo immune responses that involve immunological memory. PMID:10527694

Nelson, C J; How, T; Lysle, D T

1999-11-01

412

Morphine versus oxycodone analgesia after percutaneous kidney stone surgery: a randomised double blinded study.  

PubMed

According to previous studies oxycodone might have some advantages over morphine in the treatment of visceral pain. This study investigated the opioid consumption (primary outcome), pain relief and side effects (secondary outcomes) of morphine versus oxycodone after percutaneous nephrolithotomy using a method where the somatic pain component was minimized. Forty-four adult patients were studied. The patients were randomised to receive either morphine or oxycodone intravenously as postoperative pain treatment. During the first 4 h after surgery the opioid consumption, pain scores and side effects (nausea, dizziness, sedation, respiratory effects and itching) were registered. The postoperative opioid consumption varied considerably between the patients but the mean opioid consumption in the morphine and oxycodone group was comparable (18.93 mg versus 16.15 mg, P = 0.7). Nausea was significantly less frequent with morphine (P = 0.03). In this study morphine and oxycodone produced similar analgesia the first 4 h after surgery but the frequency of nausea was significantly less patient-reported with morphine. The hypothesis that oxycodone would be superior in the treatment of visceral pain after percutaneous kidney stone operation was not confirmed. PMID:23828457

Pedersen, Katja Venborg; Olesen, Anne Estrup; Drewes, Asbjørn Mohr; Osther, Palle Jørn Sloth

2013-10-01

413

Morphine biosynthesis in opium poppy involves two cell types: sieve elements and laticifers.  

PubMed

Immunofluorescence labeling and shotgun proteomics were used to establish the cell type-specific localization of morphine biosynthesis in opium poppy (Papaver somniferum). Polyclonal antibodies for each of six enzymes involved in converting (R)-reticuline to morphine detected corresponding antigens in sieve elements of the phloem, as described previously for all upstream enzymes transforming (S)-norcoclaurine to (S)-reticuline. Validated shotgun proteomics performed on whole-stem and latex total protein extracts generated 2031 and 830 distinct protein families, respectively. Proteins corresponding to nine morphine biosynthetic enzymes were represented in the whole stem, whereas only four of the final five pathway enzymes were detected in the latex. Salutaridine synthase was detected in the whole stem, but not in the latex subproteome. The final three enzymes converting thebaine to morphine were among the most abundant active latex proteins despite a limited occurrence in laticifers suggested by immunofluorescence labeling. Multiple charge isoforms of two key O-demethylases in the latex were revealed by two-dimensional immunoblot analysis. Salutaridine biosynthesis appears to occur only in sieve elements, whereas conversion of thebaine to morphine is predominant in adjacent laticifers, which contain morphine-rich latex. Complementary use of immunofluorescence labeling and shotgun proteomics has substantially resolved the cellular localization of morphine biosynthesis in opium poppy. PMID:24104569

Onoyovwe, Akpevwe; Hagel, Jillian M; Chen, Xue; Khan, Morgan F; Schriemer, David C; Facchini, Peter J

2013-10-01

414

Morphine modulation of pain processing in medial and lateral pain pathways  

PubMed Central

Background Despite the wide-spread use of morphine and related opioid agonists in clinic and their powerful analgesic effects, our understanding of the neural mechanisms underlying opioid analgesia at supraspinal levels is quite limited. The present study was designed to investigate the modulative effect of morphine on nociceptive processing in the medial and lateral pain pathways using a multiple single-unit recording technique. Pain evoked neuronal activities were simultaneously recorded from the primary somatosensory cortex (SI), ventral posterolateral thalamus (VPL), anterior cingulate cortex (ACC), and medial dorsal thalamus (MD) with eight-wire microelectrode arrays in awake rats. Results The results showed that the noxious heat evoked responses of single neurons in all of the four areas were depressed after systemic injection of 5 mg/kg morphine. The depressive effects of morphine included (i) decreasing the neuronal response magnitude; (ii) reducing the fraction of responding neurons, and (iii) shortening the response duration. In addition, the capability of cortical and thalamic neural ensembles to discriminate noxious from innocuous stimuli was decreased by morphine within both pain pathways. Meanwhile, morphine suppressed the pain-evoked changes in the information flow from medial to lateral pathway and from cortex to thalamus. These effects were completely blocked by pre-treatment with the opiate receptor antagonist naloxone. Conclusion These results suggest that morphine exerts analgesic effects through suppressing both sensory and affective dimensions of pain. PMID:19822022

Wang, Jin-Yan; Huang, Jin; Chang, Jing-Yu; Woodward, Donald J; Luo, Fei

2009-01-01

415

Agmatine inhibits morphine-induced memory impairment in the mouse step-down inhibitory avoidance task.  

PubMed

The effect of agmatine on memory formation in morphine-treated mice on the step-down inhibitory avoidance test was examined. Pre-training and pre-test administration of agmatine (5, 10 and 20mg/kg, s.c.) facilitated memory formation and retrieval while post-training administration of agmatine (5, 10 and 20mg/kg, s.c.) had no effect on memory consolidation. Idazoxan (5mg/kg, i.p.) inhibited the effect of agmatine on memory formation and retrieval. Pre-training administration of morphine (1.25, 2.5 and 5mg/kg, s.c.) impaired memory formation while post-training and pre-test administration of morphine (1.25, 2.5 and 5mg/kg, s.c.) had no effect on memory consolidation and retrieval. Pre-training agmatine treatment reversed the impairment of morphine on memory formation. Moreover, pre-test administration of agmatine inhibited morphine-induced amnesia. Pre-training and pre-test idazoxan (5mg/kg, i.p.) treatment inhibited the effect of agmatine on morphine induced memory impairment. In conclusion, agmatine inhibited morphine-induced memory impairment on the mice step-down inhibitory avoidance test. The mechanism was exerted, at least in part, through activation of imidazoline receptors. PMID:20801152

Lu, Wei; Dong, Hua-Jin; Gong, Zheng-Hua; Su, Rui-Bin; Li, Jin

2010-12-01

416

Morphine modifies the cingulate-operculum network underlying painful rectal evoked potentials.  

PubMed

The effect of opioids on brain networks underlying rectal evoked potentials (EPs) has never been investigated. This study utilized brain source connectivity to explore whether morphine induced changes in brain networks underlying painful rectal EPs would reflect changes in pain scores due to morphine. Twenty healthy volunteers were included in this placebo-controlled cross-over study. Sensory and pain thresholds to electrically induced rectal stimulation were taken before (baseline) and 70 min after placebo/morphine (30 mg) administration. The stimulation intensity required to evoke moderate pain at baseline was employed for EPs. The pain score of this stimulation intensity was recorded again 70 min after placebo/morphine administration. 62-channel EPs were recorded for both arms. Amplitudes and latencies were analysed and brain source connectivity analysis was done. Changes in any of the parameters describing EPs were correlated to changes in subjective pain ratings. Morphine increased sensory and pain thresholds by 28.8% and 27.5% (P ? 0.02). The pain score corresponding to moderate pain at baseline was attenuated in both placebo and morphine arms by 14.5% and 37.5% (P < 0.05). There was a 33.9% reduction in EP amplitudes due to placebo (P < 0.05), whereas EP amplitudes remained stable due to morphine. A dominating cingulate-operculum network to rectal pain was seen. Cingulate source shifted anteriorly in the morphine arm (P < 0.001) and this shift was positively correlated to the change in the pain score (r = 0.6, P < 0.05). These findings indicate that visceral pain relief due to morphine is associated with reorganization within cingulate cortex, which may be used as a biomarker of opioid effects. PMID:24184388

Lelic, D; Olesen, A E; Gregersen, H; Dahan, A; Kolesnikov, Y; Drewes, A M

2014-02-01

417

Global Changes in the Rat Heart Proteome Induced by Prolonged Morphine Treatment and Withdrawal  

PubMed Central

Morphine belongs among the most commonly used opioids in medical practice due to its strong analgesic effects. However, sustained administration of morphine leads to the development of tolerance and dependence and may cause long-lasting alterations in nervous tissue. Although proteomic approaches enabled to reveal changes in multiple gene expression in the brain as a consequence of morphine treatment, there is lack of information about the effect of this drug on heart tissue. Here we studied the effect of 10-day morphine exposure and subsequent drug withdrawal (3 or 6 days) on the rat heart proteome. Using the iTRAQ technique, we identified 541 proteins in the cytosol, 595 proteins in the plasma membrane-enriched fraction and 538 proteins in the mitochondria-enriched fraction derived from the left ventricles. Altogether, the expression levels of 237 proteins were altered by morphine treatment or withdrawal. The majority of changes (58 proteins) occurred in the cytosol after a 3-day abstinence period. Significant alterations were found in the expression of heat shock proteins (HSP27, ?-B crystallin, HSP70, HSP10 and HSP60), whose levels were markedly up-regulated after morphine treatment or withdrawal. Besides that morphine exposure up-regulated MAPK p38 (isoform CRA_b) which is a well-known up-stream mediator of phosphorylation and activation of HSP27 and ?-B crystallin. Whereas there were no alterations in the levels of proteins involved in oxidative stress, several changes were determined in the levels of pro- and anti-apoptotic proteins. These data provide a complex view on quantitative changes in the cardiac proteome induced by morphine treatment or withdrawal and demonstrate great sensitivity of this organ to morphine. PMID:23056601

Drastichova, Zdenka; Skrabalova, Jitka; Jedelsky, Petr; Neckar, Jan; Kolar, Frantisek; Novotny, Jiri

2012-01-01

418

Effects of voluntary exercise on hippocampal long-term potentiation in morphine-dependent rats.  

PubMed

This study was designed to examine the effect of voluntary exercise on hippocampal long-term potentiation (LTP) in morphine-dependent rats. The rats were randomly distributed into the saline-sedentary (Sal/Sed), the dependent-sedentary, the saline-exercise (Sal/Exc), and the dependent-exercise (D/Exc) groups. The Sal/Exc and the D/Exc groups were allowed to freely exercise in a running wheel for 10 days. The Sal/Sed and the morphine-sedentary groups were kept sedentary for the same extent of time. Morphine (10 mg/kg) was injected bi-daily (12 h interval) during 10 days of voluntary exercise. On day 11, 2h after the morphine injection, the in vivo LTP in the dentate gyrus of the hippocampus was examined. The theta frequency primed bursts were delivered to the perforant path for induction of LTP. Population spike (PS) amplitude and the field excitatory post-synaptic potentials (fEPSP) slope were measured as indices of increase in synaptic efficacy. Chronic morphine increased the mean basal EPSP, and augmented PS-LTP. Exercise significantly increased the mean baseline EPSP and PS responses, and augmented PS-LTP in both saline and morphine-treated groups. Moreover, the increase of PS-LTP in the morphine-exercise group was greater (22.5%), but not statistically significant, than that of the Sal/Exc group. These results may imply an additive effect between exercise and morphine on mechanisms of synaptic plasticity. Such an interaction between exercise and chronic morphine may influence cognitive functions in opiate addicts. PMID:24141180

Miladi-Gorji, H; Rashidy-Pour, A; Fathollahi, Y; Semnanian, S; Jadidi, M

2014-01-01

419

Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A.  

PubMed

We investigated the effects of morphine and other agonists on the human mu opioid receptor (MOP) expressed in M2 melanoma cells, lacking the actin cytoskeleton protein filamin A and in A7, a subclone of the M2 melanoma cells, stably transfected with filamin A cDNA. The results of binding experiments showed that after chronic morphine treatment (24 h) of A7 cells, MOP-binding sites were down-regulated to 63% of control, whereas, unexpectedly, in M2 cells, MOP binding was up-regulated to 188% of control naive cells. Similar up-regulation was observed with the agonists methadone and levorphanol. The presence of antagonists (naloxone or CTAP) during chronic morphine treatment inhibited MOP down-regulation in A7 cells. In contrast, morphine-induced up-regulation of MOP in M2 cells was further increased by these antagonists. Chronic morphine desensitized MOP in A7 cells, i.e., it decreased DAMGO-induced stimulation of GTPgammaS binding. In M2 cells DAMGO stimulation of GTPgammaS binding was significantly greater than in A7 cells and was not desensitized by chronic morphine. Pertussis toxin treatment abolished morphine-induced receptor up-regulation in M2 cells, whereas it had no effect on morphine-induced down-regulation in A7 cells. These results indicate that, in the absence of filamin A, chronic treatment with morphine, methadone or levorphanol leads to up-regulation of MOP, to our knowledge, the first instance of opioid receptor up-regulation by agonists in cell culture. PMID:17897634

Onoprishvili, Irma; Simon, Eric J

2007-10-26

420

Functionally Selective Signaling for Morphine and Fentanyl Antinociception and Tolerance Mediated by the Rat Periaqueductal Gray  

PubMed Central

Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and C-Jun N-terminal kinase (JNK) activation on both the expression and development of tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray of the rat. Microinjection of morphine or fentanyl into the periaqueductal gray produced a dose-dependent increase in hot plate latency. Microinjection of the non-specific GRK/PKC inhibitor Ro 32-0432 into the periaqueductal gray to block mu-opioid receptor phosphorylation enhanced the antinociceptive effect of morphine but had no effect on fentanyl antinociception. Microinjection of the JNK inhibitor SP600125 had no effect on morphine or fentanyl antinociception, but blocked the expression of tolerance to repeated morphine microinjections. In contrast, a microinjection of Ro 32-0432 blocked the expression of fentanyl, but not morphine tolerance. Repeated microinjections of Ro 32-0432 blocked the development of morphine tolerance and inhibited fentanyl antinociception whether rats were tolerant or not. Repeated microinjections of SP600125 into the periaqueductal gray blocked the development of tolerance to both morphine and fentanyl microinjections. These data demonstrate that the signaling molecules that contribute to tolerance vary depending on the opioid and methodology used to assess tolerance (expression vs. development of tolerance). This signaling difference is especially clear for the expression of tolerance in which JNK contributes to morphine tolerance and GRK/PKC contributes to fentanyl tolerance. PMID:25503060

Morgan, Michael M.; Reid, Rachel A.; Saville, Kimber A.

2014-01-01

421

Oral vaccines  

PubMed Central

Oral vaccines are safe and easy to administer and convenient for all ages. They have been successfully developed to protect from many infectious diseases acquired through oral transmission. We recently found in animal models that formulation of oral vaccines in a nanoparticle-releasing microparticle delivery system is a viable approach for selectively inducing large intestinal protective immunity against infections at rectal and genital mucosae. These large-intestine targeted oral vaccines are a potential substitute for the intracolorectal immunization, which has been found to be effective against rectogenital infections but is not feasible for mass vaccination. Moreover, the newly developed delivery system can be modified to selectively target either the small or large intestine for immunization and accordingly revealed a regionalized immune system in the gut. Future applications and research endeavors suggested by the findings are discussed. PMID:23493163