CLINICAL PHARMACOKINETICS elln. Drug Invest. 1997 Apr: 13 (4): 207·214 117?r2563/97/0CIJ4.(Y2fJ7/S04.00/0 © Adis Intemalional Umited, An rights reselVed. Effect of Renal Function on the Pharmacokinetics of Valsartan Pratapa Prasad, 1 Surinder Mangat,l Les Choi,l Sistine Chen, 1 Bee Chen,1 Angelito Bernardo,2 David Frame,2 Rita Sperelakis2 and Alan Lau 2 1 Novartis Pharmaceuticals Corporation, Summit, New Jersey, USA 2 College of Pharmacy, University of illinois at Chicago, Chicago, Illinois, USA Summary The effect of renal function on the pharmacokinetics of valsartan was inves- tigated 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 dysfunc- tion, as determined by creatinine clearance (CLcR,), were assigned to four groups: normal renal function (CLCR> 90 mVmin), and mild (CLcR 61 to 90 mVmin), moderate (CLcR 30 to 60 mVmin) and severe (CLCR < 30 mVmin) renal dysfunc- tion. 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 concentra- tion-time curve (AUC), maximum plasma valsartan concentration (Cmu), time to reach Cmax (tmax), and the terminal elimination half-life (t'/2)] were calculated. Statistical analysis using a cubic polynomial regression function was performed to examine a relationship between renal function and the pharmacokinetic para- meters of valsartan. Scatter plots of pharmacokinetic parameters did not indicate any clear relation- ship with creatinine clearance. The regression coefficients oflinear, quadratic and cubic terms for the AUC and Cmax 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 exper- iences 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.