Effects of green tea extract administration on the pharmacokinetics of clozapine in rats

The pharmacokinetic interaction between clozapine, an atypical antipsychotic with metabolic complications, including weight gain, and green tea consumption has not been evaluated, although green tea is responsible for beneficial effects, including weight reduction, and is widely consumed in the world. Commercial green tea extract (175 mg kg−1) or saline was administered orally for 4 days before the oral administration of clozapine (20 mg kg−1) to rats. Plasma concentrations of clozapine were measured up to 5 h after clozapine administration, and then hepatic CYP1A2 expression and activity were determined. There was no significant difference in the elimination half‐life of clozapine between the green tea extract and saline groups. However, the time to reach peak concentration (Tmax) was significantly increased by green tea extract. The mean total area under the plasma concentration‐time curve (AUC0‐∞) and maximal peak plasma concentration (Cmax) of clozapine in the green tea extract group were significantly lower than those of controls. Green tea extract induced a ∼2‐fold increase in hepatic CYP1A2 levels, while the activity increased slightly (by 10% of control). Because of this reduction in AUC and Tmaxof clozapine by green tea extract pretreatment, we suggest that both the rate and amount of absorption of clozapine may be reduced by green tea extract, although the hepatic elimination phase may not be significantly altered. Therefore, the clinical implications of the effects of green tea on the bioavailability of clozapine in patients should be further evaluated.