Comparative studies on pharmacokinetic fates of tetrahydropalmatine enantiomers in different chemical environments in rats

Abstract

Tetrahydropalmatine (THP) is the active component in Rhizoma corydalis and the medicine Yuanhu-Baizhi (YB), which consists of Rhizoma corydalis and Radix angelicae dahuricae. The aim of this work was to compare pharmacokinetic features of THP enantiomers in rats dosed with racemic THP (rac-THP), Rhizoma corydalis, or YB extracts. A single dose of rac-THP (5 mg kg(-1)) or extracts of Rhizoma corydalis and YB (both equivalent to 5 mg kg(-1) of rac-THP) was given orally to three groups of Sprague-Dawley rats, respectively. Blood samples were collected periodically and plasma concentrations of THP enantiomers were determined using an achiral-chiral high-performance liquid chromatographic (HPLC) method previously reported, with some modifications. The C(max) ratio (-/+) of THP was 2.91, 1.38, and 1.19, and the AUC(0 approximately infinity) ratio (-/+) of THP was 2.84, 1.50, and 1.35 in rats after dosed with rac-THP, extracts of Rhizoma corydalis and YB, respectively. The mean AUC(0 approximately infinity) and C(max) of (+)-THP dosed with YB extracts were 0.652 +/- 0.30 microg h ml(-1) and 0.148 +/- 0.09 microg ml(-1), significantly higher (P < 0.05) than those dosed with rac-THP and Rhizoma corydalis extracts. The mean AUC(0 approximately infinity) and T(max) of rac-THP dosed with YB extracts were 1.500 +/- 0.56 microg h ml(-1) and 2.12 +/- 1.1 h, significantly higher (P < 0.05) than those dosed with rac-THP or Rhizoma corydalis extracts. These findings suggested the stereoselectivity in pharmacokinetics of THP enantiomers in rats was decreased when dosed in plant form, while the AUC(0 approximately infinity) of rac-THP increased when YB extracts were dosed, confirming the compatibility in drug combination of Rhizoma corydalis and Radix angelicae dahuricae.