Effect of renal function on risedronate pharmacokinetics after a single oral dose

Aims To determine the relationship between risedronate pharmacokinetics and renal function. Methods Risedronate was administered to adult men and women (n=21) with var ious degrees of renal function (creatinine clearance 15-126 ml min(-1) ) as a single oral dose of 30 mg. Serum samples were obtained for 72 h after do sing, and urine samples were collected for 72 h after dosing and then perio dically for 6 weeks. Risedronate concentrations were determined using an en zyme-linked immunosorbent assay (ELISA). Risedronate serum concentration-ti me and urinary excretion rate-time profiles were analysed simultaneously us ing nonlinear regression. Results Renal clearance and volume of distribution were linearly related to creatinine clearance (r(2)=0.854, P < 0.001; and r(2)=0.317, P < 0.01, res pectively). Decreases in predicted renal clearance and volume of distributi on of 82 and 69%, respectively, were observed when creatinine clearance dec reased from 120 to 20 ml min(-1). A 64% decrease in predicted oral clearanc e was observed when creatinine clearance decreased from 120 to 20 ml min(-1 ) (P=0.064). Iohexol clearance, a predictor of renal function, produced sim ilar results to those observed with creatinine clearance. Risedronate was w ell tolerated by the study population. Conclusions Risedronate renal clearance was significantly related to a decr ease in renal function. There was a consistent reduction in oral clearance with a decrease in creatinine clearance. However, based on the regression a nalysis, generally no dosage adjustment appears to be necessary for most pa tients with mild or moderate renal impairment (creatinine clearance > 20 ml min(-1)).