bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: mechanisms of drug release from tablets and capsules. 2. Dissolution
Authors: MELIA C. D. , DAVIS S. S. 
Published: July 2010

SUMMARYOptimal drug dissolution is crucial to the success of oral drug therapy. Slow dissolution has frequently been correlated with poor or erratic performance of oral dosage forms in vivo, and drugs of low aqueous solubility provide a major challenge to the designer of modern oral dosage forms. In this second of two reviews, we briefly describe the physical process of dissolution, the principal factors controlling drug dissolution from tablets and capsules, and the strategies that are utilized by pharmaceutical scientists to enhance drug dissolution of orally administered drugs.Dissolution, Tablets, Drug release, Bioavailability.
Prolonged inhibition of meal‐stimulated acid secretion and gastrin release following single subcutaneous administration of octreotide (SMS 201–995) in man
Authors: KARNES W. E. , MAXWELL V. , SYTNIK B. , CHEW P. , WALSH J. H. 
Published: July 2010

SUMMARYSingle subcutaneous doses of the somatostatin analogue, SMS 201–995, were evaluated for the degree and duration of effects on acid secretion, serum gastrin levels, and gastric emptying in eight human male subjects (mean age 44 years) over an 8‐h period. All the subjects received subcutaneous 50‐μg and 100‐μg doses of SMS 201–995 and placebo on three separate days in a double‐blind random order. Drug or placebo was administered at time 0 followed by peptone meals at time 0, 2, 4, and 6‐h. Peptone meals were evacuated at time 1, 3, 5 and 7‐h to create ‘basal’conditions between alternate hours. Gastric acid secretion was determined hourly beginning at time −1. Both the 50‐μg and 100‐μg doses of SMS 201–995 significantly inhibited ‘basal’and peptone meal‐stimulated gastric acid secretion throughout the 8‐h measurement period. The minimum effective plasma concentration of SMS 201–995 for inhibition of peptone meal‐stimulated gastric acid secretion was approximately 1000 pg/ml. Peptone meal‐stimulated plasma gastrin
A double‐blind placebo‐controlled trial of omeprazole on characteristics of the migrating motor complex in healthy volunteers
Authors: VINTER‐JENSEN L. , KRAGLUND K. , PEDERSEN S. A. 
Published: July 2010

SUMMARYThe aim of the study was to investigate a possible effect of omeprazole on the characteristics of the migrating motor complex. The study was performed as a double‐blind crossover study and the pressure recordings were performed after 3 days of treatment with placebo or omeprazole 40 mg o.m. The calculations were based on 5 h of recording in each subject and in both investigations. There were two characteristics in the omeprazole group which were significantly different from placebo. Firstly, duodenal phase III was more often accompanied by an antral phase III and secondly, the duration of duodenal phase III was increased. The results suggest that the rapid cleaning mechanism, represented by phase III activity, is more pronounced after omeprazole treatment, possibly arising from its antisecretory effect.
The relationship between suppression of acidity and gastric ulcer healing rates
Authors: HOWDEN C. W. , HUNT R. H. 
Published: July 2010

SUMMARYWe have investigated the relationship between the suppression of acidity by antisecretory drugs for the treatment of benign gastric ulcer and their corresponding ulcer‐healing rates. For a variety of antisecretory drug regimens, there was a significant correlation between suppression of 24‐h intragastric acidity and ulcer healing rates after 2, 4 and 8 weeks of treatment. There was a lesser degree of correlation between healing and suppression of nocturnal acidity and the association between suppression of acidity and gastric‐ulcer healing rates was less marked than that previously described for duodenal ulcer.
The value of flumazenil in the reversal of midazolam‐induced sedation for upper gastrointestinal endoscopy
Authors: DUNK A. A. , NORTON A. C. , HUDSON M. , DUNDAS C. R. , MOWAT N. ASHLEY G. 
Published: July 2010

SUMMARYFifty patients who underwent diagnostic upper gastrointestinal endoscopy after midazolam sedation were randomized to receive (after completion of the examination) either the benzodiazepine receptor antagonist flumazenil or an identical‐looking placebo. The speed of recovery from sedation was assessed by reaction time testing, measurement of critical flicker fusion frequency, and the semi‐quantitative SOCA scoring system. Measurements were made up to 6 h post examination in all subjects, and at 12 and 24 h in all in‐patients (n= 20). Flumazenil‐treated patients were significantly more alert than those who received placebo at 10 min, 30 min, 1 h and 2 h (P < 0.001 in all instances). Thereafter the two groups were similar. There was no evidence of recurrence of sedation in flumazenil‐treated patients, nor did this drug adversely affect the period of anterograde amnesia between the administration of midazolam and flumazenil.
Rapid intravenous low‐dose diazepam as sedation for upper gastrointestinal endoscopy
Authors: SWAIN D. G. , ELLIS D. J. , BRADBY H. 
Published: July 2010

SUMMARYOne hundred patients for endoscopy, aged, between 18 and 74 years were randomly allocated to two equal groups. Group A received 10 mg diazepam intravenously rapidly over 2–4 s; Group B received diazepam intravenously over 1–2 min, titrated to provide a satisfactory level of sedation (mean dose 15.9 mg).Patient co‐operation during endoscopy was similar in both groups, but one patient in Group A developed respiratory depression. Tests of psychomotor function after endoscopy showed greater impairment 30 min following injection for Group B, compared with Group A (P < 0.02).Total or partial amnesia for endoscopy was present in 62% of Group A, and 90% in Group B (P < 0.005). However, postal follow‐up showed that endoscopy was acceptable to 96% of Group A and 98% of Group B. Delayed sedation later in the day was reported by 26% of Group A compared with 48% of Group B.
Intravenous omeprazole: effect of a loading dose on 24‐h intragastric pH
Authors: ANDERSEN J , STRÖM M. , NÆSDAL J. , LEIRE K. , WALAN A. 
Published: July 2010

SUMMARYTo determine the effect of three times daily dosing with intravenous omeprazole on intragastric acidity, 24 h intragastric pH was measured continuously with a monocrystalline antimony electrode system in 11 patients with inactive duodenal ulceration during fasting conditions. After a baseline investigation, two different dosage regimens of intravenous omeprazole were compared in a double‐blind crossover study, with regard to their ability to keep the pH ≥ 4 for as long as possible. Success in the individual patient was defined as pH ≥ 4 for at least 90% over the 24‐h period. Two doses of omeprazole [40 mg t.d.s. (120 mg) and 80 mg + 40 mg + 40 mg (160 mg)] were compared.Omeprazole (120 mg) increased the median of individual median intragastric 24‐h pH from 1.49 to 6.67. The pH was ± 4 for ≥ 90% of the 24 h in three of the 11 patients. With omeprazole, 160 mg (a loading dose of 80 mg), the median of individual median intragastric 24‐h pH increased to 7.33. The pH was ≥ 4 for ≥ 90% of the 24 h in seven of the 11 patients. Median time to reach pH 4 was 39 min after 40 mg and 20 min after 80 mg omeprazole.An initial loading dose of 80 mg omeprazole seems preferable to 40 mg to achieve a fast and sustained increase in intragastric pH to above 4 in the fasting patient.
Review article: premedication and intravenous sedation for upper gastrointestinal endoscopy
Authors: BELL G. D. 
Published: July 2010

SUMMARYUpper gastrointestinal endoscopy can be performed without intravenous sedation but the evidence suggests that, in the United Kingdom and United States, most patients and endoscopists prefer that some form of premedication is given. Intravenous diazepam or midazolam are used by the majority of endoscopists. In the UK, the ratio of diazepam to midazolam users is approximately 2:1, while in the USA more endoscopists are now using midazolam. Midazolam is approximately twice as potent as diazepam but, when allowance is made for this, there is probably little or no difference in the propensity of the two drugs to produce respiratory depression. The antegrade amnesic effect of midazolam is significantly superior to that of diazepam. A benzodiazepine/narcotic combination can achieve a smoother and more rapid induction with less gagging and choking, but the incidence of adverse outcomes—particularly respiratory depression—is increased significantly. Over 50% of the deaths that are associated with upper gastrointestinal endoscopy are due to cardiopulmonary problems. Hypoxia is very common if measured using non‐invasive monitoring equipment, such as a pulse oximeter. Methods of preventing oxygen desaturation and thus, by inference, most cardiac arrhythmias associated with endoscopy are discussed, as is the role of flumazenil, the new benzodiazepine antagonist.
Amino acid tolerance in cirrhotic patients following oral protein and amino acid loads
Authors: MORGAN M. Y. , HAWLEY K. E. , STAMBUK D. 
Published: July 2010

SUMMARYPlasma amino acid and venous blood ammonia concentrations were measured in six patients with well‐compensated cirrhosis and in six healthy volunteers, both in the fasting state and serially for 5 h following ingestion of 30 g mixed protein and 30 g amino acid mixture, administered on separate occasions.Mean fasting plasma concentrations of threonine, serine, proline, glycine, and of the three branched‐chain amino acids, valine, isoleucine and leucine, were significantly reduced in the cirrhotic patients compared with the control subjects, while mean (μ 1 s.d.) fasting venous blood ammonia concentrations were comparable 71.2 ± 31.4 cf. 56.0 ± 25.4 μmol/LFollowing the oral protein and amino acid loads, increases were observed in plasma amino acid concentrations in the majority of subjects with a return to baseline values by the end of the study. Changes in the circulating concentrations of most amino acids were independent of their concentration in the oral protein and amino acid loads, and their relative distribution in the circulation varied over time. The increases in the concentrations of the three branched‐chain amino acids did, however, reflect their concentrations in the two nitrogen loads and did remain constant, relative to one another, over time.
Some effects of tripotassium dicitrato bismuthate on gastric secretion and the mucus barrier
Authors: SIDEBOTHAM R. L. , BATTEN J. J. , LI K. , SPENCER J. , BARON J. H. 
Published: July 2010

SUMMARYThe effect of tripotassium dicitrato bismuthate (De‐Nol) on the breakdown of the gastric mucus barrier was investigated by measuring the output of mucus glycoprotein in pentagastrin‐stimulated secretion from 13 patients before and after treatment for peptic ulcer, and by examining the accumulation of dialysable peptides and amino acids (DPAA) in stimulated secretion from ten of these patients. The accumulation of DPAA was significantly reduced after De‐Nol (by 54%) and to a greater extent than was the output of mucus glycoprotein (by 27%). These observations are consistent with a decrease in the rate of breakdown of the mucus barrier as a result of De‐Nol treatment. De‐Nol significantly reduced pepsin output (by 32%) in the same group of patients. Comparison of the change in pepsin output with the change in accumulation of DPAA in stimulated juice indicated that De‐Nol increases the resistance of the mucus barrier to acid‐pepsin proteolysis and/or inhibits the secretion of amino acids and peptides from gastric mucosa.
The timing of the evening meal affects the pattern of 24‐hour intragastric acidity
Authors: LANZON‐MILLER S. , POUNDER R. E. , MCISAAC R. L. , WOOD J. R. 
Published: July 2010

SUMMARYThe object of the study was to examine the effect of varying the time of the evening meal on the pattern of 24‐h intragastric acidity. Ten healthy subjects were studied; they ate regular meals throughout the day, but between 17.00 and 21.35 hours were separated into three groups. On three different days each group was fed the same dinner at either 17.15, 19.15, or 21.15 hours (early, standard or late). Variation in the evening meal's time caused significant changes in the pattern of acidity in the afternoon and evening, but did not affect 24‐h intragastric acidity or nocturnal acidity. Integrated afternoon acidity (14.00 hours to dinner) was 69, 169 and 324 mmol. h/L when the subjects ate early, standard and late meals, respectively; evening acidity (dinner to midnight) was 235, 43 and 1 mmol. h/L with the three meals, respectively. The results suggest that, to control intragastric acidity, when the evening meal is eaten early (17.15 hours) dosing with an H2‐antagonist should be after that meal, when eaten at the standard time (19.15 hours) dosing should be at bedtime, but when dinner is late (21.15 hours) the optimal regimen may involve dosing after lunch and also at bedtime.
In‐vivo anti‐reflux and raft properties of alginates
Authors: LAMBERT J. R. , KORMAN M. G. , NICHOLSON LESLEY , CHAN J. G. 
Published: July 2010

SUMMARYThe comparative efficacy of two alginate‐containing anti‐reflux preparations (Gaviscon, Algicon) was assessed in a single blind crossover study of 20 patients with gastro‐oesophageal reflux disease. The clinical efficacy study was preceded by two studies in healthy volunteers to assess the intragastric effects of Algicon and Gaviscon by pH measurement, endoscopic visualization and gamma scintigraphy.Algicon and Gaviscon were shown to form a raft in the fasting and fed human stomach, with Algicon alone having a potent antacid effect below and within the raft. Both Algicon and Gaviscon liquids significantly reduced the frequency and severity of reflux symptoms from baseline when given at their recommended doses (10 ml and 20 ml four times daily, respectively). There were no significant differences between Algicon and Gaviscon, although 12 patients preferred Algicon (vs 5 for Gaviscon) for control of reflux symptoms. It was concluded that both Algicon and Gaviscon were effective for the symptomatic control of gastro‐oesophageal reflux disease.
Inhibition of gastrin‐ and histamine‐stimulated gastric acid secretion by gastrin and cholecystokinin antagonists in the rat
Authors: HIRST B. H. , ELLIOTT K. J. , RYDER H. , SZELKE M. 
Published: July 2010

SUMMARYThe gastric acid inhibitory activities of a peptide‐like gastrin receptor antagonist, Boc‐βAla‐Trp‐Leu‐Asp‐O(CH2)2‐Ph‐4‐F (CH‐486), a non‐peptide gastrin/CCK‐B antagonist (L‐365,260), and a CCK‐A antagonist (L‐364,718), were investigated in the gastric lumen‐perfused anaesthetized rat. A single i.v. injection of CH‐486, 100 μmol/kg, reduced acid secretion stimulated by pentagastrin, 15 μg kg/h, to unstimulated levels, with no recovery within 50 min. Histamine‐, 0.1 μmol kg/min, and carbamylcholine‐, 0.1 mg kg/h, stimulated acid secretion were also reduced to unstimulated levels by CH‐486, 100 μmol/kg, although with these latter two stimulants the inhibition was transient. L‐365,260 and L‐364,718, 10 μmol/kg, significantly inhibited both pentagastrin‐ and histamine‐stimulated acid secretion, the latter again transiently. We conclude that the non‐selective nature of the gastric acid inhibitory activity of gastrin antagonists might allow novel approaches to control gastric acid secretion in peptic ulcer disease.
Comparison of rat and human intestinal perfusion models for assessing efficacy of oral rehydration solutions
Authors: HUNT J. B. , ELLIOTT E. J. , FARTHING M. J. G. 
Published: July 2010

SUMMARYThe optimal composition for oral rehydration solutions remains controversial. Animal models have been used to assess the efficacy of new formulations but the relevance of these studies to the handling of oral rehydration solutions in human intestine during diarrhoeal disease states remains uncertain. Using steady state perfusion techniques we have compared water and solute transport from a variety of oral rehydration solutions in both the entire rat small intestine and in the human jejunum. Overall the pattern of water, sodium and glucose absorption was similar from the three oral rehydration solutions tested, indicating close parallelism between the two models despite the species and methodological differences. Although the relationship between the findings of these studies to the handling of oral rehydration solution in diarrhoeal disease states remains uncertain, we believe they do support the view that animal models may have a part to play in the preliminary screening of oral rehydration solutions before clinical trial.
Review article: improved preservation of the liver for transplantation
Authors: JAMIESON N. V. 
Published: July 2010

SUMMARYThis paper reviews the development of the techniques used for liver preservation and describes their clinical use. Recent advances with the introduction of lactobionate based solutions for simple cold storage are described and illustrated by their effect on the Cambridge/King's College Hospital transplant programmes. Better preservation of the liver has simplified the logistics of the transplant procedure, improving organ usage and allowing increased sharing of livers for urgent or paediatric cases.
Nocturnal therapy with famotidine for 1 year is effective in preventing relapse of gastric ulcer
Authors: BERLIN R. G. , ROOT J. K. , COOK T. J. 
Published: July 2010

SUMMARYA multicentre, double‐blind, randomized, placebo‐controlled trial was undertaken to investigate the therapeutic efficacy of a nocturnal dose of famotidine 20 mg to reduce the 1 year relapse rate of recently healed gastric ulcers. Twenty investigators in eight countries randomized 202 patients with endoscopically confirmed healed gastric ulcers. Repeat endoscopies were performed at 6 and 12 months or for symptoms compatible with ulcer relapse. A per protocol analysis of cumulative life table relapse at 12 months showed that famotidine 20 mg was superior to placebo in reducing gastric ulcer relapse, 24 versus 50%, respectively (P < 0.01). Both placebo and famotidine were well tolerated. Since nocturnal dosing with famotidine 20 mg is effective in preventing gastric ulcer relapse over a 1‐year period and is well tolerated, it offers a therapeutic option for the long‐term treatment of patients with gastric ulcer.
The effect of ranitidine, cimetidine or famotidine on low‐dose post‐prandial alcohol absorption
Authors: FRASER A. G. , PREWETT E. J. , HUDSON M. , SAWYERR A. M. , ROSALKI S. B. , POUNDER R. E. 
Published: July 2010

SUMMARYPlasma alcohol concentration following oral ingestion of 0.3 g/kg of alcohol (ethyl alcohol), one hour after an evening meal, was measured in four groups of 12 healthy subjects. Each group had a control study and a repeat study after 7 days dosing with either placebo or an H2‐receptor antagonist (300 mg ranitidine nocte, 800 mg cimetidine nocte, or 40 mg famotidine nocte). There was no significant difference between the control and post‐dosing studies in the integrated 4‐h plasma alcohol concentration, peak plasma alcohol concentration, or time to reach peak alcohol concentration. This study shows that post‐prandial alcohol absorption after 0.3 g/kg of alcohol is not affected by ranitidine, cimetidine or famotidine.
Hydroxyproline in the oesophageal mucosa of patients with progressive systemic sclerosis during omeprazole‐induced healing of reflux oesophagitis
Authors: HENDEL L. 
Published: July 2010

SUMMARYHydroxyproline concentration in oesophageal mucosal biopsies was used as an index of collagen in an attempt to evaluate the potential for stricture formation in patients with progressive systemic sclerosis. Eight patients suffering from progressive systemic sclerosis with complicating gastro‐oesophageal reflux, 8 patients with idiopathic gastro‐oesophageal reflux, and 7 normal controls were compared. Acid gastro‐oesophageal reflux was assessed with 24‐h pH‐metry; degree of oesophagitis was evaluated both endoscopically and histopathologically. The patients with progressive systemic sclerosis were investigated at the start of the study and later when healing of oesophagitis was accomplished with omeprazole therapy. The hydroxyproline concentration was significantly increased (P < 0.01) in the oesophageal mucosa from patients with progressive systemic sclerosis (median 21.8 nmol/mg) as compared to patients with idiopathic gastro‐oesophageal reflux (median 6.4 nmol/mg) and normal controls (median 8.1 nmol/mg).Hydroxyproline concentration in oesophageal mucosa from patients with progressive systemic sclerosis decreased significantly and to a normal level (median 6.5 nmol/pg; P= 0.014) when healing of oesophagitis was achieved.
Cisapride in the treatment of post‐operative ileus
Authors: HALLERBÄCK B. , BERGMAN B. , BONG H. , EKSTRÖM P. , GLISE H. , LUNDGREN K. , RISBERG O. 
Published: July 2010

SUMMARYThe effect of cisapride on duration of post‐operative ileus after surgery was investigated in a randomized, double‐blind, placebo‐controlled study. Patients undergoing elective upper gastrointestinal (n= 47) or colonic (n= 22) surgery were pre‐operatively randomly allocated to treatment with either cisapride 30 mg t.d.s., by rectal administration, or placebo. Treatment started exactly 48 h after surgery if the patient at this time had not passed stool. Time to passage of first stool after surgery was estimated.Mean time to passage of stool was 85 (32) h (s.d.) for cisapridetreated and 91 (43) h for placebo‐treated patients. No difference between the treatment groups was noted.Treatment with cisapride did not shorten the duration of postoperative ileus after either upper gastrointestinal or colonic surgery.
The pro‐drug sulindac may reduce the risk of intestinal damage associated with the use of conventional non‐steroidal anti‐inflammatory drugs
Authors: DAVIES G. R. , RAMPTON D. S. 
Published: July 2010

SUMMARYTo test the hypothesis that administration of a non‐steroidal anti‐inflammatory drug formulated as a pro‐drug, inactive as a cyclooxygenase inhibitor until after absorption, might cause less intestinal damage than conventional non‐steroidal anti‐inflammatory drugs, intestinal permeation to 51Cr‐EDTA and mannitol was assessed in healthy volunteers before and after oral treatment for 1 week with either the pro‐drug sulindac or the conventional non‐steroidal anti‐inflammatory drug indomethacin. Indomethacin, but not sulindac, significantly increased intestinal permeation to 51Cr‐EDTA and reduced haemoglobin and haematocrit; neither affected mannitol permeation.
Effects of ranitidine, given t.d.s., on intragastric and oesophageal pH in patients with gastrooesophageal reflux
Authors: RUSSELL J. , ORR W. C. , WILSON T. , FINN A. L. 
Published: July 2010

SUMMARYThe purpose of this study was to determine the effects of 150 mg ranitidine, 300 mg ranitidine or placebo, administered every 8 h, on gastro‐oesophageal pH and heartburn parameters in reflux patients. Twelve symptomatic reflux patients received each of the three treatments in a randomized, double‐blind, crossover fashion. Intragastric and oesophageal pH were monitored continuously for a 24 h period. Meals were standardized, consumed at set times and patients were allowed to recline and sleep from 23.00 hours until 06.00 hours only. The gastric record was analysed for the percentage of time that the pH was ≧ 4. The oesophageal record was analysed for acid contact time (percentage time (%) pH ≦ 4.0) and reflux episode frequency. Finally, patients recorded each new episode of heartburn and graded daytime heartburn severity at the end of each hour. Ranitidine increased the median (%) time that the intragastric pH remained at or above 4, from 4.5 (placebo) to 33.9% (150 mg dose) and 33.3% (300 mg dose). Ranitidine dose‐dependently reduced the median 24‐hour oesophageal acid contact time from 13.3% (placebo) to 6.8% (150 mg dose) and 2.5% (300 mg dose). The 300 mg dose significantly reduced daytime heartburn episode frequency and severity while the 150 mg dose reduced heartburn severity only. We conclude that 150 and 300 mg doses of ranitidine administered every 8 h have major, sometimes dose‐dependent effects on the objective parameters and symptoms of gastro‐oesophageal reflux.