Comparative pharmacokinetics of periplocin and its four key metabolites in rats after oral administration of periplocin and cardiac glycoside extract from Cortex Periplocae

Introduction Cortex Periplocae has been demonstrated to possess a variety of pharmacological effects, particularly in the treatment of chronic heart failure, attributed largely to its cardiac glycosides particularly periplocin. Methods In order to gain a deeper understanding of the pharmacokinetic behaviors of periplocin and its metabolites, and to elucidate the influence of the cardiac glycoside extract matrix on their dynamic process in vivo , an ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-S-MS/MS) method was developed and successfully applied to a comparative pharmacokinetic study in rats following oral administration of either pure periplocin (50 mg/kg) or cardiac glycoside extract from Cortex Periplocae (100 mg/kg, equivalent to approximately 52 mg/kg periplocin). Results The results showed that periplocin was absorbed rapidly in both groups (Tmax≤0.60 h). However, the extract matrix significantly altered the metabolic exposure. Compared with the periplocin group, the cardiac glycoside extract group demonstrated significantly higher levels of gomphogenin, with a marked increase in both C max and AUC (0-∞) . Conversely, the systemic exposures AUC (0-∞) of periplocymarin and 17 α -asclepioside were significantly reduced. Furthermore, double peaks were observed in the concentration-time curves of gomphogenin and periplogenin, suggesting potential enterohepatic circulation. Discussion These findings reveal that the complex matrix alters the bioavailability of active metabolites, providing a crucial kinetic basis for optimizing clinical dosage regimens and safety monitoring of Cortex Periplocae .