Green Tea Extract Affects the Cytochrome P450 3A Activity and Pharmacokinetics of Simvastatin in Rats

• Published in: DRUG METABOLISM AND PHARMACOKINETICS Vol. 28; no. 6; pp. 514 - 518
• Main Authors: Misaka, Shingen, Kawabe, Keisuke, Onoue, Satomi, Werba, José Pablo, Giroli, Monica, Watanabe, Hiroshi, Yamada, Shizuo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 2013; Japanese Society for the Study of Xenobiotics
• Subjects: Animals; Camellia sinensis - chemistry; CYP3A; Cytochrome P-450 CYP3A - metabolism; Cytochrome P-450 CYP3A Inhibitors; Female; green tea extract; Microsomes, Liver - drug effects; Microsomes, Liver - metabolism; midazolam; Midazolam - metabolism; pharmacokinetics; Plant Extracts - pharmacology; rat; Rats; simvastatin; Simvastatin - pharmacokinetics; Troleandomycin - pharmacology; pharmacokinetics; simvastatin; CYP3A; rat; green tea extract; midazolam
• ISSN: 1347-4367; 1880-0920; 1880-0920
• DOI: 10.2133/dmpk.DMPK-13-NT-006

Effects of green tea extract (GTE) on the activity of cytochrome P450 (CYP) enzymes and pharmacokinetics of simvastatin (SIM) were investigated in rats. Inhibitory effects of GTE on CYP3A activity were investigated in rat hepatic microsomes (RHM) using midazolam (MDZ) 1′-hydroxylation as a probe reaction. SD female rats received a single oral dose of GTE (400mg/kg) or troleandomycin (TAO, a CYP3A selective inhibitor, 500mg/kg), followed 30min later by SIM (20mg/kg). Plasma concentrations of SIM and its active metabolite, simvastatin acid, were determined up to 6h after the SIM administration using LC/MS/MS. In RHM, GTE inhibited MDZ 1′-hydroxylation with IC50 and Kiapp values of 12.5 and 18.8μg/mL, respectively, in a noncompetitive manner. Area under plasma concentration-time curves for SIM in the GTE and TAO groups were increased by 3.4- and 10.2-fold, respectively, compared with the control. The maximum concentrations of SIM were higher in the GTE (3.3-fold) and TAO (9.5-fold) groups. GTE alters the pharmacokinetics of SIM, probably by inhibiting intestinal CYP3A.