The Pharmacokinetics of Bleomycin in Man

Abstract

The pharmacokinetics of the antineoplastic antibiotic bleomycin in patients with neoplastic disorders was investigated. Drug was administered by long (4-5 days) and short (10 min) zero-order infusions, and serial plasma and urine samples were collected. Serum and urine bleomycin concentrations were determined by radioimmunoassay. The disposition of bleomycin after the 10-min infusion was described by a 2-compartment open model. Following multiple-day infusion estimates were obtained that were inconsistent with those from the short infusion. Parameters from the long infusions agreed with those from the short infusion when terminal plasma bleomycin levels less than 10 .mu.U/ml were excluded. The time to reach steady state following the long infusion (.apprx. 12 h) was consistent with the half-life (3 h) predicted by the short infusion and long infusion excluding levels < 10 .mu.U/ml. Possible explanations include assay interference by an unknown metabolite or strong binding of drug to tissues with release at a rate less than the apparent rate of elimination of drug from the body.