The pharmacokinetics and bioavailability of three canthinone alkaloids after administration of Kumu injection to rats

Abstract

Ethnopharmacological relevanceKumu injection (KMI) is made from the branches and stems of Picrasma quassiodes (D. Don) Benn. and has been used clinically for the treatment of upper respiratory tract infection, acute tonsillitis, enteritis and bacillary dysentery. 3-methylcanthin-2,6-dione, 5-hydroxy-4-methoxycanthin-6-one, 4,5-dimethoxycanthin-6-one are the active ingredients of KMI because of its therapeutic effects. Aim of the studyTo develop a LC-MS/MS method for simultaneous determination of three active canthinone alkaloids (4,5-dimethoxycanthin-6-one, 5-hydroxy-4-methoxycanthin-6-one and 3-methylcanthin-2,6-dione) in rat plasma and for the pharmacokinetic study of them after administered of KMI to rats. Materials and methodsRats were divided into 5 groups (n=5 per group), 3 groups administered intramuscularly with a single dose of KMI at 0.30, 0.45 and 0.90mL/kg respectively, and the other 2 groups administered intragastically or intravenously a single dose of KMI at 0.9mL/kg respectively. The concentrations of 4,5-dimethoxycanthin-6-one, 5-hydroxy-4-methoxycanthin-6-one and 3-methylcanthin-2,6-dione in plasma were determined by the established LC–MS/MS method at different time points and the pharmacokinetic parameters were estimated by non-compartmental analysis. ResultsPharmacokinetic results indicated that all of the alkaloids were absorbed rapidly and 3-methylcanthin-2,6-dione was eliminated fastest in rats. After intramuscular administration of KMI to rats, the absolute bioavailability is excellent, and the pharmacokinetic profiles are characterized by the first order kinetics. ConclusionThe established method is suitable for the quantitation of the three alkaloids in rat plasma. And this pharmacokinetic study suggested that intramuscular injection of KMI was suitable in clinical usage.