Search PubMed⌕ Search

Biomedical subjects

H Hoensch

Publications and source records attributed to H Hoensch.

31 records · Page 2Linked to original sources
PubMed1976

Oxidative metabolism of foreign compounds in rat small intestine: cellular localization and dependence on dietary iron.

Oxidative metabolism of foreign compounds was measured in the intestinal mucosa of male rats. Activities of benzpyrene hydroxylase, p-nitroanisole O-demethylase, and NADPH-cytochrome P-450 reductase and cytochrome P-450 content were 3 to 10 times higher in epithelial cells of the upper villus than in mucosal crypt cells. Villous tip cells of the upper small intestine exhibited much higher cytochrome P-450 content and drug-metabolizing enzyme activity than did tip cells of lower intestinal segments. In rats fed commercial chow diet, cytochrome P-450 content and drug-metabolizing enzyme activity in villous tip cells of duodenal mucosa were higher than in animals fed a semisynthetic diet, but cytochrome b5 and NADPH-cytochrome P-450 reductase were unaffected. On restriction of dietary iron intake, cytochrome P-450 and oxidative enzyme activity fell sharply, but were completely restored in 24 hr by oral iron supplementation, whereas parenteral iron administration was ineffective. These findings suggest that intestinal drug metabolism is localized primarily in the upper villous cells of the proximal intestinal mucosa, that cytochrome P-450 is synthesized in maturing epithelial cells as they migrate from the crypts to the tip of the mucosal villi, and that this process is dependent critically upon absorption of iron from the intestinal lumen.

Animals↗
PubMedDate not supplied

Interactions and non-interactions with ranitidine.

At present, there are two H2-receptor antagonists available for the treatment of peptic ulcer disease - cimetidine and ranitidine. Cimetidine is well known to interact with a number of concurrently administered drugs. Like cimetidine, ranitidine binds to cytochrome P-450 in the liver where it appears to exert an inhibitory effect, but to a lesser extent than cimetidine. Both H2-receptor antagonists may also reduce hepatic blood flow. Several drugs which are known to interact with cimetidine have been found not to interact significantly with ranitidine, including propranolol, lignocaine, phenytoin and diazepam. However, significant pharmacokinetic interactions between ranitidine and several other drugs have been established. These interactions may be attributed variously to an effect of ranitidine on hepatic metabolism or to an effect on the absorption of concomitantly administered drugs. For example, the bioavailability of midazolam is significantly increased due to the influence of ranitidine on gastric pH and thus on absorption of midazolam, leading to an increased soporific effect of this benzodiazepine; an effect of ranitidine on oxidative liver metabolism also appears to be a contributory factor in this interaction. Conversely, ranitidine distinctly reduced protein-bound cobalamin absorption from a mean of 7.66% prior to ranitidine administration to 0.84% during treatment with ranitidine 300 mg daily. A significant pharmacokinetic interaction has also been demonstrated between ranitidine and procainamide: the AUC of procainamide increased and the renal clearance fell significantly from a mean of 378 to 309 ml/min with ranitidine co-administration. However, this interaction is due to a different mechanism. In this case, ranitidine appears to compete with procainamide for the common renal proximal tubular secretion site. The reported interactions of ranitidine with warfarin, metoprolol, nifedipine, theophylline and fentanyl appear to be due to inhibition of cytochrome P-450. In a clinical study, warfarin clearance was significantly reduced from 66.7 to 48.7 ml/min by ranitidine, and by cimetidine to 42.9 ml/min. Similarly, the elimination half-lives of metoprolol and nifedipine were distinctly prolonged and the AUCs significantly increased by ranitidine. However, the latter pharmacokinetic interactions appear unlikely to be of clinical significance since the clinical effects of metoprolol and nifedipine were unaffected by ranitidine treatment. In therapeutic concentrations, ranitidine inhibited the disappearance of fentanyl from an in vitro microsomal preparation, indicating that it inhibits microsomal drug metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗