Renal and Nonrenal Clearance of Clodronate in Patients with Malignancy and Renal Impairment

Abstract

The short term pharmacokinetics of the bisphosphonate clodronate were studied in 20 patients with tumour-mediated bone disease and a wide range of renal function (creatinine clearance 13 to 112 ml/min; mean 54.8 ml/min). Clodronate 300mg was given as a single intravenous infusion over 2 hours and the concentration of drug in serum and urine was measured at intervals for 24 hours after the start of the infusion. The total clearance was 86.6 ± 7.4 ml/min (mean ± SEM), with an apparent renal clearance of 41.0 ± 4.3 ml/min, and thus a nonrenal clearance of 45.6 ± 5.2 ml/min. The range of nonrenal clearance was as great as that of renal function. Both renal and total clearance showed a significant positive correlation with renal function, as judged by endogenous creatinine clearance (r = 0.66, p = 0.002 and r = 0.62, p = 0.004, respectively). The slope of the regression line of renal clearance on creatinine clearance was 0.46, but renal clearance of clodronate exceeded creatinine clearance in 7 patients, 6 of whom had marked renal impairment. Neither nonrenal clearance nor half-life correlated significantly with renal function.