title: Inhibition of the metabolism of brotizolam by erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in brotizolam metabolism.
abstract: OBJECTIVE
  To obtain in vivo evidence for the involvement of cytochrome P450 (CYP) 3A4 in the metabolism of brotizolam.
  
  
  METHODS
  Fourteen healthy male volunteers received erythromycin 1200 mg day(-1) or placebo for 7 days in a double-blind randomized crossover manner. On the 6th day they received a single oral 0.5-mg dose of brotizolam, and blood samplings were performed for 24 h.
  
  
  RESULTS
  Erythromycin treatment significantly increased the peak plasma concentration (P < 0.05), total area under the plasma concentration-time curve (P < 0.01), and elimination half-life (P < 0.01) of brotizolam.
  
  
  CONCLUSIONS
  The present study provides in vivo evidence for the involvement of CYP3A4 in brotizolam metabolism.
authors.affiliation: Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Tokairin
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukasawa
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui-Furukori
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Aoshima
authors.forename: Akihito
authors.initials: A
authors.lastname: Suzuki
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Inoue
authors.forename: Tomonori
authors.initials: T
authors.lastname: Tateishi
authors.forename: Koichi
authors.initials: K
authors.lastname: Otani
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001381:Azepines / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004311:Double-Blind Method; D004917:Erythromycin / Q000008:administration & dosage*; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage*
chemical_list: D001381:Azepines; D006993:Hypnotics and Sedatives; D011500:Protein Synthesis Inhibitors; C020960:brotizolam; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human