Purpose: The purpose of this study was to determine the pharmacokinetic parameters of pentostatin in renally impaired patients in order to establish dosing guidelines for this population.
Methods: Pentostatin doses were administered as 15-min intravenous infusions to patients based on their measured creatinine clearance (CLcr) as follows. Patients with normal renal function (NRF), defined as CLcr >60 ml/min, received 4 mg/m(2) repeated every14 days. Patients with impaired renal function (IRF) included those with CLcr 41-60 ml/min who received 3 mg/m(2) and those with CLcr 21-40 ml/min who received 2 mg/m(2), also repeated every 14 days. Heparinized plasma samples were collected during drug infusion and out through 96 h after dosing, except in two patients in whom sampling was extended to 144 h after dosing. Urine sampling extended to 96 h after dosing, and all samples were analyzed by a validated enzyme immunoassay for pentostatin concentrations.
Results: Enrolled in the study were 13 patients (7 IRF and 6 NRF), of whom 12 contributed samples for pharmacokinetic analysis. Median baseline CLcr values were 71.5 ml/min for NRF patients and 44 ml/min for IRF patients. Following the end of intravenous infusion, pentostatin plasma concentrations declined biexponentially with time. In some patients there was a transient increase in pentostatin equivalents 2 to 4 h after dosing. There was a good correlation between measured CLcr and pentostatin total plasma clearance. The AUC(0- infinity ) values seen in IRF patients, at lower doses, were within the range of the AUC(0- infinity ) values seen in patients with normal CLcr. Toxicities observed in the two groups of patients were similar.
Conclusions: The pentostatin doses used in the study appear to be appropriate for administration to cancer patients with varying degrees of renal impairment.