Publication Date:
2011-11-18
Description:
Abstract 2476 Background: Bendamustine is a unique alkylating agent which combines a nitrogen mustard moiety of mechlorethamine with a benzimidazole. This study was conducted to characterize the distribution, metabolism, and elimination of [14C] bendamustine and its metabolites (M3, M4, and dihydroxy bendamustine [HP2]) and to assess the roles of renal and hepatic pathways in the drug's metabolism and excretion. A secondary objective was to further characterize the safety profile of single-agent bendamustine. Methods: This open-label, phase I study enrolled 6 patients, age ≥18 years, with confirmed relapsed or refractory malignancy. The study was divided into 2 assessment periods: period A, during which the mass balance and pharmacokinetics of [14C] bendamustine were investigated, and period B, an extended-use period of up to 6 cycles with non-labeled bendamustine, during which safety continued to be assessed. Patients received intravenous (IV) bendamustine (120 mg/m2), containing 80–95 μCi of [14C] bendamustine, on day 1 of cycle 1 and non-labeled IV bendamustine (120 mg/m2) on day 2 of cycle 1 (period A). Pharmacokinetic parameters of bendamustine and metabolites M3, M4, and HP2 were calculated through plasma and urine concentrations, which were determined through 24 hours following administration of bendamustine on day 1. Total radioactivity (TRA) levels were measured in plasma, urine, and feces collected prior to drug administration and at time points through 168 hours after patients received [14C] bendamustine. Collection of excreta could continue (after the 7-day period) on an outpatient basis: if radiolabeled bendamustine ≥1% of dose was measurable in the 144- to 168-hour urine or feces collection, collection continued until the recovery in each 24-hour urine or feces collection was
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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