Pharmacokinetic interactions between green tea extract and clozapine in rats

초록

Clozapine, an atypical antipsychotic with narrow therapeutic index and metabolic complications including weight gain, is mainly metabolized by cytochrome P450 1A2 (CYP1A2), CYP3A4 and flavin-containing monooxygenase (FMO). Green tea is responsible for the beneficial effects including weight reduction and is widely consumed in the world. However, the pharmacokinetic interactions between green tea and clozapine have not been evaluated. Therefore, we evaluated the pharmacokinetic interactions between clozapine (CLZ) and commercially available green tea extract (GTE) in rats. GTE (20mg/kg of EGCG), caffeine (9mg/kg), or saline was administered orally for 3 days before the oral administration of clozapine (20mg/kg). When GTE was given, 2 and 1.1folds induction of hepatic CYP1A2 content and activity were observed respectively. There was no significant difference of Cmax was observed between GTE and control groups, however, the tmax was significantly increased by GTE administration not by caffeine comparing with the control. The AUC of CLZ was not significantly different among the treated groups. Our results suggest that the pharmacokinetics of CLZ can be altered by green tea consumption especially in the absorption phase although the significant interaction between GTE and CLZ is unlikely to occur. (Supported by BK-21)