Comparative pharmacokinetics of three monoester-diterpenoid alkaloids after oral administration of Acontium carmichaeli extract and its compatibility with other herbal medicines in Sini Decoction to rats.

Abstract

Sini decoction (SND) is an important traditional Chinese multiherbal formula, which is widely used to treat cardiovascular disease. Acontium carmichaeli (AC) is a leading herb in SND, whose main components are monoester-diterpenoid alkaloids (MDAs). The aim of this study is to compare the pharmacokinetics of three MDAs in rat plasma after oral administration of AC extract and its compatibility with other herbal medicines in SND. A sensitive, accurate and specific LC-MS/MS method was developed to determine the contents of three MDAs in rat plasma. Male Sprague-Dawley rats were randomly assigned to four groups: AC, AC + ZO, AC + GU and SND groups. There were significant differences in the pharmacokinetic parameters (Cmax, Tmax, t1/2, AUC(0-24), MRT and CL). Compared with the AC group, Cmax, AUC(0-24) and CL of three MDAs increased and t1/2 decreased in AC + ZO, AC + GU and SND groups. Little changed in the AC + GU group in comparison with AC + ZO group, which indicated that other ingredients in ZO may promote the absorption rate and accelerate excretion rate of MDAs. The results could be helpful for revealing the compatibility mechanism of Chinese multiherbal medicine and providing clinical medication guidance on AC and its compatibility with other herbal medicines in SND.