摘要:

SUMMARYThe bioavailability of orally administered drugs may be reduced due to presystemic elimination. The first‐pass effect can occur in the gastrointestinal tract, the liver and lung. Although the liver is the main drug metabolizing organ in the body, the gut wall can play an important role in the first‐pass metabolism of certain drugs. Both phase I (preconjugation) and phase II (conjugation) reactions have been described. However, while the oxidative metabolic capacity of the intestinal mucosa is considerably smaller than that of the liver, the activity of conjugation reactions in the gut may be close to that of the liver, and in some cases may exceed it. Sulphate conjugation is particularly important for steriod hormones such as ethinyloestradiol, and for the β‐adrenoceptor stimulants isoprenaline and isoetharine. Glucuronidation has been demonstrated to occur in man for morphine, paracetamol and oestrogens. Significant drug—drug interactions have been described involving drugs undergoing sulphate conjugation. The study of intestinal metabolismin vivois difficult in man since direct methods (for example, hepatic portal vein catheterization) is justified in only a small number of patients. Therefore, much of our present understanding has been derived from various in‐vitro studies involving intestinal sheets, mucosal biopsies, isolated enterocytes and microsomal pr

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1987.tb00634.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYAchieving a substantial reduction in the bacterial flora of the gut is a theoretically attractive means of treating inflammatory bowel disease, particularly colonic disease. There are practical difficulties in obtaining a sustained reduction of the colonic bacterial count, and the potential role of such a treatment regimen is therefore the initiation of remission. The data in the literature supporting such a suggestion are anecdotal, and a controlled study is indicated.

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1987.tb00635.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1987.tb00636.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYAll available ranitidine and cimetidine comparative trials in acute duodenal ulcer disease were examined: of the 44 trials, 36 favoured ranitidine, and there was an overall difference in ulcer healing of 7%. Further stratification enabled examination of trials with common attributes: the most frequent endoscopic assessment was at 4 weeks to compare ranitidine 150 mg twice daily with cimetidine 1 g day−1or 400 mg b.d. Twenty of these trials had sufficient data to permit pooling. Ranitidine was favoured in 18/20 trials and in three the differences achieved statistical significance. Results of the trials were combined using meta‐analysis to calculate differences in ulcer healing. Most studies had sample sizes that were insufficient to detect clinically‐important differences; the power to detect a 20% difference was less than 80% in 15/20 trials, and for a 10% difference was less than 80% in all but one trial. Fifteen trials compared ranitidine 150 mg b.d. with cimetidine 1 g day−1: healing after 4 weeks therapy was overall 6% greater for ranitidine. This was statistically significant (P<0.05) and the combined total number of patients had a power of 83% to detect this difference. In five trials the dose of cimetidine used was 400 mg b.d.: the 12% difference in healing in favour of ranitidine 150 mg b.d. was statistically significant, and the combined trials had a power of 95% to detect this difference. Ranitidine 150 mg twice daily heals significantly more duodenal ulcers after 4 weeks of therapy than either cimetidine 400 mg b.d. or cimetidine 1

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1987.tb00637.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYAspirin induces gastric mucosal damage in animals and humans. The purpose of this study was to examine whether cimetidine protects the human gastric mucosa from acute aspirin‐induced damage. Eight healthy subjects were studied on 4 separate days. Cimetidine, 400 mg, or placebo was given orally 1 hour before initial endoscopy. The stomach was isolated and atropine given to suppress basal acid secretion. Each study consisted of four 15 min periods during which an acidic test solution was instilled into the stomach. During the second period only, either aspirin (1300 mg, 36 mmol) or control for aspirin (36 mmol HCl) was added to the test solution. Ion fluxes and gastric mucosal potential difference were measured, and endoscopy performed following each test. After placebo, aspirin significantly altered hydrogen ion flux and potential difference versus basal and control. Cimetidine decreased the damaging effect of aspirin. Endoscopic scores increased after aspirin plus placebo, whereas they remained unchanged after aspirin plus cimetidine. Therefore, cimetidine decreased aspirin‐induced gastric mucosal damage in humans. As gastric acidity was identical during all studies, the effect of cimetidine was independent of gastric acid secret

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1987.tb00638.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYPrednisolone absorption was studied in 13 normal subjects, eight patients with ulcerative colitis and 21 patients with Crohn's disease, by measuring plasma levels after a single oral dose. Absorption of the drug was delayed in all patient groups. The peak plasma level of the drug was lower in patients with extensive small bowel Crohn's disease. Patients in this category may need higher doses of oral prednisolone than other patients with inflammatory bowel disease.

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1987.tb00639.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYPaired studies were carried out on 18 healthy male volunteers (20.9 ± 1.9 years; mean ± S.D.) to compare the effect of oral doses of the H2‐receptor antagonists, ranitidine and cimetidine, on the rate of gastric emptying of radiolabelled solid and liquid test meals. Oral administration of ranitidine 300 mg accelerated the emptying of a liquid meal from the stomach, but it had no significant effect on the rate of emptying of a solid meal. Oral administration of either 400 or 800 mg cimetidine did not alter the rate of emptying of either the liquid or the solid meals from the stom

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1987.tb00640.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYIn a study of 101 patients undergoing upper gastrointestinal endoscopy, 90% of patients had complete amnesia for the procedure after intravenous midazolam (average dose 10 mg), but only 61% had complete amnesia after intravenous diazepam in lipid emulsion (average dose 18.4 mg) (P= 0.0006). However, when assessed by two different tests, recovery within the first hour was significantly more rapid after diazepam (P<0.0001). Prolonged sedation (over 20 hours after injection) was reported occasionally by patients who had received either drug. Thus, as with patients who have been sedated with diazepam, those who have been sedated with midazolam should also be advised to avoid driving or operating machinery for at least 24 hours after injection.

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1987.tb00641.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYIn the present in‐vitro study we investigated the possible role of the calmodulin‐antagonistic drugs loperamide and calmidazolium in the regulation of transepithelial Ca2+transport of human duodenum. Brush border membrane vesicles and basolateral membrane vesicles were simultaneously prepared from surgically resected pieces of morphologically intact human duodenum with a modified Percoll‐gradient centrifugation method. Brush border and basolateral membrane vesicles were characterized using enzyme marker analysis and electron microscopy: alkaline phosphatase was enriched 20‐fold in brush border membrane vesicles, whereas [Na++ K+]‐stimulated adenosine triphosphatase was enriched 15‐fold in basolateral membrane vesicles. Calmodulin activity was determined by a specific radioimmunoassay after solubilizing brush border and basolateral membrane vesicles in 1% Triton X‐100. In basolateral membrane vesicles, we found no calmodulin activity. In brush border membrane vesicles calmodulin activity was impaired by 50% after pre‐incubation with loperamide or calmidazolium. We measured calcium, sodium,d‐glucose andd‐mannitol uptake with a rapid filtration technique. Before the transport experiments, brush border and basolateral membrane vesicles were pre‐incubated with 5 μM loperamide or 5 μM calmidazolium for 60 min at 5 °C. In drug‐pretreated, brush border membrane vesicles calcium uptake was signficantly reduced after 1 min incubation (– 25%±5%,P<0.05); this effect was completely reversed in the presence of 5 μM calmodulin. In basolateral membrane vesicles, we found two Ca2+transport systems: (1) Na+/Ca2+exchange and (2) ATP‐dependent Ca2+transport. In basolateral membrane vesicles loperamide had no effect. Calmidazolium had no effect on Na+/Ca2+exchange, but significantly inhibited ATP‐dependent Ca2+transport. This effect c

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1987.tb00642.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYStudies were carried out on 22 healthy male volunteers to investigate whether intravenous administration of either the opiate antagonist, naloxone, or the dopamine antagonist, domperidone, or the α2‐adrenoreceptor antagonist, idazoxan, could reverse the delay in gastric emptying induced by ileal infusion of lipid emulsion. Ileal infusion of 50% lipid emulsion signficantly delayed the rate of gastric emptying compared with ileal infusion of isotonic saline (P<0.01). Intravenous infusion of naloxone (20 μg kg−1hour−1) or prior administration of either intravenous domperidone (20 mg) or idazoxan (0.2 mg kg−1) did not inhibit the delay in gastric emptying induced by ileal infusion of lipid emulsion. These observations indicate that feedback regulation of gastric emptying by ileal lipid does not appear to be mediated by either dopaminergic or enkephalinergic neurons, nor by α2‐adr

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1987.tb00643.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY