title: Rifampicin markedly decreases plasma concentration and hypnotic effect of brotizolam.
abstract: The purpose of the present study was to examine the effects of rifampicin on the single oral dose pharmacokinetics and pharmacodynamics of brotizolam. Thirteen healthy male volunteers received rifampicin 450 mg/day, or matched placebo, for 7 days in a double-blind randomized crossover manner. On the sixth day they received a single oral 0.5-mg dose of brotizolam, and blood sampling was performed for 24 hours, together with an assessment of psychomotor function using the Digit Symbol Substitution Test and the Stanford Sleepiness Scale. Rifampicin treatment significantly (P<0.001) decreased the peak plasma concentration (69%), total area under the plasma concentration-time curve (90%) and elimination half-life (79%) of brotizolam. Rifampicin significantly increased the area under the score-time curve of the Digit Symbol Substitution Test (P<0.01), and decreased that of the Stanford Sleepiness Scale (P<0.05). The present study suggests that rifampicin markedly decreases plasma concentration and hypnotic effect of brotizolam and, therefore, this combination is not recommended in clinical practice.
authors.affiliation: Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Ujiie
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukasawa
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui-Furukori
authors.forename: Akihito
authors.initials: A
authors.lastname: Suzuki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Tateishi
authors.forename: Koichi
authors.initials: K
authors.lastname: Otani
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001381:Azepines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D001381:Azepines; D006993:Hypnotics and Sedatives; C020960:brotizolam; D012293:Rifampin