Pharmacokinetic interaction study between ligustrazine and valsartan in rats and its potential mechanism

Ligustrazine and valsartan are commonly used drugs in the treatment of cardiac and cardiovascular disease. The interaction between ligustrazine and valsartan was studied to investigate the effect of ligustrazine on the pharmacokinetics of valsartan. The pharmacokinetics of valsartan (10 mg/kg) was investigated in Sprague–Dawley rats divided into three groups (with the pretreatment of 4 or 10 mg/kg/day ligustrazine for 10 days and without the pretreatment of ligustrazine as control) of six rats each. The in vitro experiments in rat liver microsomes were performed to explore the effect of ligustrazine on the metabolic stability of valsartan. Ligustrazine changed the pharmacokinetic profile of valsartan. In the presence of 4 mg/kg ligustrazine, the AUC(0–t) (385.37 ± 93.05 versus 851.64 ± 104.26 μg/L*h), t1/2 (5.46 ± 0.93 versus 6.34 ± 1.25 h), and Cmax (62.64 ± 9.09 versus 83.87 ± 6.15 μg/L) of valsartan was significantly decreased, and the clearance rate was increased from 10.92 ± 1.521 to 25.76 ± 6.24 L/h/kg and similar changes were observed in the group with 10 mg/kg ligustrazine (p