Article date: March 2000
By: D. Y. Mitchell, J. V. St. Peter, R.A. Eusebio , K. A. Pallone, S. C. Kelly, D. A. Russell, J. D. Nesbitt, G. A. Thompson, J. H. Powell, in Volume 49, Issue 3, pages 215-222
Aims To determine the relationship between risedronate pharmacokinetics and renal function.
Methods Risedronate was administered to adult men and women (n=21) with various 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 dosing, and urine samples were collected for 72 h after dosing and then periodically for 6 weeks. Risedronate concentrations were determined using an enzyme‐linked immunosorbent assay (ELISA). Risedronate serum concentration‐time and urinary excretion rate‐time profiles were analysed simultaneously using nonlinear regression.
Results Renal clearance and volume of distribution were linearly related to creatinine clearance (r2=0.854, P<0.001; and r2=0.317, P<0.01, respectively). Decreases in predicted renal clearance and volume of distribution of 82 and 69%, respectively, were observed when creatinine clearance decreased from 120 to 20 ml min−1. A 64% decrease in predicted oral clearance was observed when creatinine clearance decreased from 120 to 20 ml min−1 (P=0.064). Iohexol clearance, a predictor of renal function, produced similar results to those observed with creatinine clearance. Risedronate was well tolerated by the study population.
Conclusions Risedronate renal clearance was significantly related to a decrease in renal function. There was a consistent reduction in oral clearance with a decrease in creatinine clearance. However, based on the regression analysis, generally no dosage adjustment appears to be necessary for most patients with mild or moderate renal impairment (creatinine clearance >20 ml min−1 ).
DOI: 10.1046/j.1365-2125.2000.00135.x
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