Effects of Zuojin Pill (Rhizoma CoptidisandFructus Evodiaepreparation) on the pharmacokinetics and side effects of venlafaxine in humans

Abstract Venlafaxine (VEN), a first‐line antidepressant, and Zuojin Pill (ZJP), a common herbal medicine consisting of Rhizoma Coptidis and Fructus Evodiae , are high likely co‐administered in China. ZJP could significantly inhibit VEN pharmacokinetics in vitro and in rats through suppression of CYP2D6 activity. To date, however, no clinical study has demonstrated the clinical relevance. Here, the VEN pharmacokinetics at a single dose of VEN with or without co‐administration of ZJP was compared. ZJP had a weak herb–drug interactions (HDI) on the pharmacokinetics of VEN. The geometric means of C max and AUC 0‐∞ of VEN increased by 36.7% and 34.6%, respectively, and the corresponding 90% confidence intervals (CIs) of geometric mean ratios (GMRs) exceed outside bioequivalent range of 0.80–1.25. However, the corresponding 90% CIs of GMRs of these parameters for ODV were within the range. Since ODV exposure (AUC), approximately 3.4‐fold higher than that of VEN, hardly changed, the systemic exposure of VEN active moiety (VEN + ODV) with ZJP increased slightly (≤8.5%) compared with that of VEN alone. In addition, the incidence of VEN‐related side effects, especially gastrointestinal relevance, was significantly reduced with ZJP. Therefore, rational concomitant use of VEN and ZJP might have low risk of HDI and be promising in clinical practice.