RENAL AND NONRENAL CLEARANCE OF CLODRONATE IN PATIENTS WITH MALIGNANCY AND RENAL IMPAIRMENT

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. We conclude that there is no need to adjust the dose interval of clodronate in patients with renal impairment, but that the dose of clodronate should be reduced in the presence of markedly impaired renal function. However, the range of nonrenal clearance is high, so that difficulties arise in dose adjustments made on the basis of renal function alone.