Inhibitory effect of ketoconazole, quinidine and 1-aminobenzotriazole on pharmacokinetics of tetrahydropalmatine and its metabolite in rats.

tetrahydropalmatine (THP) is mainly metabolised by CYP450 enzymes.This study was to investigate the possible effect of co-administered CYP inhibitors on the pharmacokinetics of THP and its metabolites in rats.An established LC-MS/MS method has been applied for the evaluation of drug-drug interaction between THP and CYP inhibitors. Following the administration of CYP inhibitors, a single dose of THP (9 mg/kg) was orally administrated.With regard to THP, the AUC were significantly increased by 4.3, 3.79, and 11.39 folds, and were increased by 4.74, 3.64, and 2.76 folds in the ketoconazole group (KET), quinidine group (QD), and 1-aminobenzotriazole group (ABT), respectively. KET and QD both significantly increased the AUC of 2-DM and 2-DM-Glu by 1.38 ∼ 2.43 times, while was significantly decreased by 41.3 and 78.0% in the ABT group, respectively. The of 3-DM was reduced by 51.38, 48.02, and 63.31% after pre-treatment with KET, QD, and ABT, respectively, and of 3-DM-Glu decreased correspondingly by 29.6, 22.1, and 58.0%.Results indicated that CYP inhibitors could markedly influence the systemic level of -THP and its metabolites. To guarantee the safe use of -THP, attention should be paid when -THP was co-administered with CYP inhibitors, particularly with CYP3A4 and 2D6 inhibitors.