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- W2077370521 abstract "Mexazolam, a benzodiazepinooxazole-anxiolytic, was first N-dealkylated to M1 and then hydroxylated to lorazepam in rat liver microsomes. The production of M1 in vitro was inhibited by SKF-525 A, carbon monoxide and in the atmosphere of nitrogen. The heat-treated microsomes, the omission of an NADPH-generating system and the substitution of NADPH with NADH showed practically no activity. The microsomes obtained from the phenobarbital treated rats showed increased activity toward both the production of M1 and lorazepam from mexazolam, but the clofibrate and 3-methylcholanthrene treatments failed to induce this activity. Cimetidine inhibited non-competitively both steps in the metabolism of mexazolam: mexazolam to M1 (Ki: 375 μM) and M1 to lorazepam (Ki: 390 μM). Ranitidine did not inhibit in vitro metabolism of mexazolam at the concentrations so far investigated ( ?? 400 μM). The pretreatment of rats with cimetidine (200 mg/kg, i.p.) 30 min prior to the administration of mexazolam (50 mg/kg, i.p.), increased AUC and the plasma half-life of mexazolam 8.8-fold and 7.7-fold, respectively. On the other hand, the co-administration of ranitidine did not change the pharmacokinetic parameters of mexazolam." @default.
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- W2077370521 date "1988-01-01" @default.
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- W2077370521 title "Interaction of Cimetidine and Ranitidine, the H<SUB>2</SUB>-Receptor Blockers, with Mexazolam, a Benzodiazepinooxazole-Anxiolytic in Rats" @default.
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- W2077370521 doi "https://doi.org/10.2133/dmpk.3.395" @default.
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