EFFECT OF RENAL-FUNCTION ON THE PHARMACOKINETICS OF VALSARTAN

The effect of renal function on the pharmacokinetics of valsartan was investigated in this trial. In order to cover the full spectrum of ren al function, a total of 19 subjects with normal renal function and var ious degrees of renal dysfunction, as determined by creatinine clearan ce (CLCR, were assigned to four groups: normal renal function (CLCR 90 ml/min), and mild (CLCR 61 to 90 ml/min), moderate (CLCR 30 to 60 ml/ min) and severe (CLCR < 30 ml/min) renal dysfunction. Creatinine clear ance 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 co llected at frequent intervals up to 48 hours postdose and plasma valsa rtan concentrations were determined. Pharmacokinetic parameters [area under the plasma concentration-time curve (AUC), maximum plasma valsar tan concentration (C-max) time to reach C-max (t(max)) and the termina l elimination half-life (t 1/2)] were calculated. Statistical analysis using a cubic polynomial regression function was performed to examine a relationship between renal function and the pharmacokinetic paramet ers of valsartan. Scatter plots of pharmacokinetic parameters did not indicate any clear relationship with creatinine clearance. The regress ion coefficients of linear, quadratic and cubic terms for the AUC and C-max of valsartan versus renal function were not significantly differ ent from zero. Thus, the pharmacokinetics of valsartan did not correla te with renal function. In addition, no clinically significant adverse experiences were observed in this trial; the 80mg dose of valsartan w as well tolerated. Based on these observations, there is no rationale for dosage adjustment of valsartan in patients with impaired renal fun ction.