In vivo integrated pharmacokinetics of four flavonoids of Abelmoschus manihot extract in rats

Abstract

Objective: To establish an HPLC method for determination of four flavonoids concentration in blood plasma and investigate their pharmacokinetics and bioavailability after ig and iv administration of extracts in corolla of Abelmoschus manihot (EAM) in rats. Methods: An HPLC-UV method was established and validated for the simultaneous determination of flavonoids, hyperin, isoquercitrin, hibifolin, quercetin-3′-O-glucoside in rat plasma. Pharmacokinetic parameters of each compound were calculated using DAS software. A novel approach of self-defined weighting coefficient based on the area under the curve from zero to infinity (AUC0-∞) had been created to obtain the holistic pharmacokinetic profiles of EAM. The integrated pharmacokinetic parameters of EAM were then calculated from both typical compartment and non-compartmental model analysis. The absolute bioavailabilities were calculated based on the (AUC0-∞) values. Results: A good linearity was obtained at 0.1-8 μg/mL of flavonoids in rat plasma with r > 0.99. The quantitive restriction was 0.1 μg/mL, the recovery rate was over 70%. The RSD of intra- and inter-day was less than 15%. The pharmacokinetic parameters of flavonoids were different from each other after ig and iv administration. The absolute bioavailability of flavonoids were 12.9%, 10.8%, 2.2%, 10.2% and 5.9%, respectively. Conclusion: The method is sensitive, specific, accurate, and is not only useful for guiding the bioavailability study on the corolla of A. manihot, but also for establishing a reasonable clinical dosage program. The four flavonols in the corolla of A. manihot can be rapidly distributed and eliminated in rats, the pharmacokinetics of two routes of administration are different. A novel integrated pharmacokinetic approach to describing the holistic pharmacokinetic properties of Chinese materia medica has been successfully developed and validated using four flavonols of A. manihot as a model herbal medicine. This study would be a new try for guiding the holistic pharmacokinetic study in consistence with the intrinsic theory and characteristics of traditional Chinese medicine.