Oxypeucedanin (OPD) is a linear furanocoumarin extracted from Chinese herbs, which has been reported to exhibit various pharmacological effects such as analgesia, antitussive, anticancer and anti-inflammatory activities. In this paper, the tissue distribution, excretion and metabolism characteristics of OPD in rat was conducted in order to better understand this compound and for potential development of OPD as a medicine. We first used the established HPLC/MS/MS method to examine the plasma protein binding rate and the tissue distribution of OPD in rats after oral administration. The excretion characteristics of OPD in urine, feces and bile, as well as its metabolic profiles in plasma, urine and bile were also investigated. The results demonstrated that after OPD administration, extensive metabolism occurred in rats, involving first-pass effect and enterohepatic circulation, with significant sex differences observed in the metabolic process. The study identified eight metabolites in rats, indicating that OPD metabolism primarily occurs through oxidation, reduction, and glucuronidation. In summary, this study systematically examined the basic process of OPD in vivo, providing a robust foundation for accurately predicting the behavior, efficacy and safety of OPD in humans.
Oxypeucedanin, a furanocoumarin extracted from many traditional Chinese herbal medicines, has a variety of pharmacological effects. However, the independent pharmacokinetic characteristics and bioavailability of this compound remains elusive. In this study, a rapid, sensitive, and selective method using ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC/MS/MS) was developed for evaluating the intravenous and oral pharmacokinetics of oxypeucedanin. After intravenous administration of oxypeucedanin (2.5, 5, and 10 mg/kg), and intragastric administration of oxypeucedanin (20 mg/kg), blood samples were collected periodically from the tail vein. The plasma concentration-time curves were plotted, and the pharmacokinetic parameters were calculated using a non-compartmental model analysis. After intravenous administration of oxypeucedanin (single dosing at 2.5, 5, and 10 mg/kg) to rats, the pharmacokinetics fit the linear kinetics characteristics, which showed that some parameters including average elimination half-life (T1/2Zof 0.61~0.66 h), mean residence time (MRT of 0.62~0.80 h), apparent volume of distribution (VZof 4.98~7.50 L/kg), and systemic clearance (CLZof 5.64~8.55 L/kg/h) are dose-independent and the area under concentration-time curve (AUC) increased in a dose-proportional manner. Single oral administration of oxypeucedanin (20 mg/kg) showed poor and slow absorption with the mean time to reach the peak concentration (Tmax) of 3.38 h, MRT of 5.86 h, T1/2Zof 2.94 h, and a mean absolute bioavailability of 10.26% in rats. These results provide critical information for a better understanding of the pharmacological effect of oxypeucedanin, which will facilitate its research and development.Keywords:oxypeucedanin;pharmacokinetics;bioavailability;UPLC/MS/MS;rats
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