[The pharmacokinetics of lormetazepam following cimetidine].
Cimetidine delays the elimination from plasma of those benzodiazepines that are subject to oxidative drug metabolism. An open-label cross-over study was conducted to discover whether cimetidine also changes the plasma level profile of lormetazepam. METHODS. Ten volunteers (5 female, 5 male) took part in the study. After oral administration of 1 mg lormetazepam alone followed by a 6-day washout phase, the subjects received five 200-mg cimetidine tablets at intervals of 6 h (Table 1). The subjects took another 1-mg dose of lormetazepam p.o. together with the last tablet of cimetidine. Blood was sampled at specified intervals after both lormetazepam administrations, and the concentration of the drug in the plasma was determined by means of a specific radioimmunoassay. RESULTS. Cimetidine had no influence on the plasma levels of lormetazepam (Fig. 1). The drug concentrations increased quickly after both treatments regardless of sex and reached their highest values 1-2 h after oral ingestion. half-lives of 30-40 min were determined for the beta-phase and 8-10 h for the terminal elimination phase (Table 2). DISCUSSION. Lormetazepam, over 90% of which is excreted in humans as lormetazepam glucuronide, like oxazepam and lorazepam, does not obviously interact with cimetidine. All other benzodiazepines, which have to undergo oxidation before excretion, interact with drugs that inhibit the microsomal (cytochrome-P-450-dependent) enzyme system. CONCLUSION. In this study, no influence of simultaneous administration of cimetidine--a well-known inhibitor of P-450 dependent drug metabolism--on the pharmacokinetics of lormetazepam in either men or women was observed. This is in agreement with theoretical considerations: due to a 3-hydroxy group, lormetazepam does not require oxidation (hydroxylation) before it is metabolized into a water-soluble form capable of being excreted from the body. Cimetidine is therefore unlikely to potentiate the sedative effect of lormetazepam.
Institut für Anaesthesiologie der Ludwig-Maximilians-Universität, Bereich Innenstadt, München.
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Doenicke
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Dorow
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Täuber
D014151:Anti-Anxiety Agents / Q000097:blood / Q000493:pharmacokinetics*; D001569:Benzodiazepines; D002927:Cimetidine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008140:Lorazepam / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D002927:Cimetidine; C023842:lormetazepam; D008140:Lorazepam
Die Pharmakokinetik von Lormetazepam nach Cimetidin.