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• W2114089215 abstract "Midazolam is a short-acting benzodiazepine that is metabolized by CYP3A enzymes. Rifampin is a potent enzyme inducer that may seriously interact with some substrates of CYP3A4.The possible interaction between rifampin and midazolam was investigated in a double-blind, randomized crossover study of two phases. Rifampin (600 mg once daily) or placebo was administered to 10 healthy subjects for 5 days. On the sixth day, the subjects were given 15 mg oral midazolam. Plasma samples were collected for determination of midazolam, and pharmacodynamic effects were measured for 10 hours.Rifampin pretreatment decreased the area under the plasma midazolam concentration-time curve by 96% (i.e., from 10.2 +/- 0.8 to 0.42 +/- 0.05 micrograms.min/ml [mean +/- SEM; p < 0.001]) and the maximum concentration by 94% (i.e., from 55 +/- 4 to 3.5 +/- 0.7 ng/ml [p < 0.001]). The elimination half-life of midazolam was decreased from 3.1 +/- 0.2 to 1.3 +/- 0.2 hours by rifampin (p < 0.001). During the rifampin phase, the pharmacodynamic effects of midazolam were markedly smaller than the effects during the placebo phase in all the tests (e.g., the Digit Symbol Substitution Test; p < 0.001).The observed substantial decrease in plasma concentrations and effects of midazolam most likely results from induction of CYP3A4 by rifampin in both the gut wall and the liver. Orally administered midazolam is ineffective during rifampin treatment." @default.
• W2114089215 created "2016-06-24" @default.
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• W2114089215 date "1996-01-01" @default.
• W2114089215 modified "2023-10-06" @default.
• W2114089215 title "Rifampin drastically reduces plasma concentrations and effects of oral midazolam" @default.
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• W2114089215 doi "https://doi.org/10.1016/s0009-9236(96)90018-1" @default.
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