Transient inhibition of cyp3a in rats by star fruit juice.
Star fruit juice is a potent in vitro inhibitor of CYP3A; however, few reports are available on the inhibition of CYP3A activities by star fruit juice in vivo. Therefore, in this study, we investigated the CYP3A-mediated star fruit-drug interaction in vivo. The effect of star fruit juice on carbamazepine pharmacokinetics was examined in rats. In comparison with water, the area under the concentration-time curve (AUC) of carbamazepine was approximately 1.3-fold greater when star fruit juice (2 ml) was orally administered 1 h before the oral administration of carbamazepine (50 mg/kg). In contrast, the elimination half-life of carbamazepine and the AUC ratio of carbamazepine 10,11-epoxide to carbamazepine were not altered by the administration of star fruit juice. These results suggest that star fruit juice impairs the function of enteric CYP3A, but not of hepatic CYP3A. In addition, we evaluated the time course of recovery of CYP3A activity that was reduced after the treatment with star fruit juice. The inhibition by star fruit juice was recovered within approximately 24 h. These data suggest that the effect of star fruit juice is mainly reversible and transient. Thus, we discovered that star fruit juice alters the carbamazepine pharmacokinetics in rats.
Hidaka
Muneaki
M
Department of Pharmacy, Miyazaki Medical College Hospital, 5200 Kihara, Kiyotake-cho, Miyazaki-gun, 889-1692, Japan. yshidaka@med.miyazaki-u.ac.jp
Okumura
Manabu
M
Ogikubo
Tetsuya
T
Kai
Hirofumi
H
Fujita
Ken-ichi
K
Iwakiri
Tomomi
T
Yamasaki
Keishi
K
Setoguchi
Nao
N
Matsunaga
Naoya
N
Arimori
Kazuhiko
K
D000818:Animals; D019540:Area Under Curve; D001628:Beverages / Q000009:adverse effects; D001682:Biological Availability; D002220:Carbamazepine / Q000493:pharmacokinetics; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors / Q000009:adverse effects; D018565:Food-Drug Interactions; D005638:Fruit; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017208:Rats, Wistar
D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D002220:Carbamazepine; D051544:Cytochrome P-450 CYP3A