Effect of Renal Function on the Pharmacokinetics of Valsartan

Summary

The effect of renal function on the pharmacokinetics of valsartan was investigated in this trial. In order to cover the full spectrum of renal function, a total of 19 subjects with normal renal function and various degrees of renal dysfunction, as determined by creatinine clearance (CL_CR), were assigned to four groups: normal renal function (CL_CR > 90 ml/min), and mild (CL_CR 61 to 90 ml/min), moderate (CL_CR 30 to 60 ml/min) and severe (CL_CR < 30 ml/min) renal dysfunction. Creatinine clearance was determined following a 24-hour urine collection just prior to drug administration. Each subject received a single oral dose of 80mg of valsartan (capsule) after an overnight fast. Blood samples were collected at frequent intervals up to 48 hours postdose and plasma valsartan concentrations were determined. Pharmacokinetic parameters [area under the plasma concentration-time curve (AUC), maximum plasma valsartan concentration (C_max), time to reach C_max (t_max), and the terminal elimination half-life (t_½)] were calculated. Statistical analysis using a cubic polynomial regression function was performed to examine a relationship between renal function and the pharmacokinetic parameters of valsartan.

Scatter plots of pharmacokinetic parameters did not indicate any clear relationship with creatinine clearance. The regression coefficients of linear, quadratic and cubic terms for the AUC and C_max of valsartan versus renal function were not significantly different from zero. Thus, the pharmacokinetics of valsartan did not correlate with renal function. In addition, no clinically significant adverse experiences were observed in this trial; the 80mg dose of valsartan was well tolerated. Based on these observations, there is no rationale for dosage adjustment of valsartan in patients with impaired renal function.