Gender differences in corydaline pharmacokinetics in rats

Abstract1. Corydaline, an isoquinoline alkaloid, is one of the major active constituents in a new prokinetic botanical agent, DA-9701. It has been recommended that preclinical pharmacokinetic studies of natural medicines include both genders. Therefore, in this study, the pharmacokinetics of corydaline in male and female rats was evaluated following intravenous and oral administration of pure corydaline or DA-9701.2. After intravenous administration of corydaline, the area under the plasma concentration–time curve (AUC) was significantly greater (by 46.4%) in female rats compared to male rats due to a 29.3% reduction in non-renal clearance in female rats. The gender difference in corydaline hepatic metabolic clearance was supported by a significantly slower metabolism of corydaline in hepatic microsomes of female rats mediated via male-specific (CYP2C11 and CYP3A2) or male-dominant (CYP3A1) CYP isozymes.3. Following oral administration of pure corydaline or DA-9701, the AUC and Cmax values of corydaline i...