Inhibition of the metabolism of brotizolam by erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in brotizolam metabolism.
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.
Tokairin
Takaki
T
Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan.
Fukasawa
Takashi
T
Yasui-Furukori
Norio
N
Aoshima
Toshiaki
T
Suzuki
Akihito
A
Inoue
Yoshimasa
Y
Tateishi
Tomonori
T
Otani
Koichi
K
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*
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