Evaluation of a pharmacokinetic interaction between valsartan and simvastatin in healthy subjects.

Objective: The potential for a pharmacokinetic drug interaction between valsartan, an antihypertensive drug, and simvastatin, a lipid-lowering agent, was investigated in this study. This was an open-label, multiple-dose, randomized, three-period, cross over study in 18 healthy subjects. Each subject received one 160 mg valsartan tablet or one 40 mg simvastatin tablet or co-administration of valsartan (160 mg) and simvastatin (40 mg) tablets for 7 days, with a 7-day inter-dose washout period. The steady-state pharmacokinetics of valsartan, simvastatin β-hydroxy acid (active metabolite of simvastatin) and simvastatin (pro-drug) were determined on day 7 of each dosing period.Results: The results were interpreted based on the point estimates and the 90% confidence intervals. These results indicated that the area under the curve of plasma concentration from 0 to 24 hours (AUC(0–24)) of valsartan, simvastatin β-hydroxy acid and simvastatin was increased by 14%, 19%, and 23%, respectively, with the combination treatment. In addition, the maximum concentration (Cmax) of valsartan and simvastatin β-hydroxy acid was increased by 10% and 22%, respectively, and the Cmax of simvastatin was decreased by 26% with the combination treatment. All treatments were safe and well tolerated.Conclusions: Based on the wide therapeutic dosage ranges of valsartan and simvastatin, and the highly variable pharmacokinetics of three analytes, the observed differences in the exposure and Cmax of valsartan, simvastatin β-hydroxy acid and simvastatin in the combination treatment are unlikely to be of clinical relevance. [ABSTRACT FROM AUTHOR]