Pharmacokinetics of Erwinia asparaginase after intravenous and intramuscular administration

Purpose: To describe the pharmaco ki ne tics of Erwinia asparaginase (ASNas e) after intravenous (i.v.) and intramuscular (i.m.) administration. Method s: A group of 29 children with newly diagnosed acute lymphoblastic leukemia (ALL) received Erwinia ASNase 30,000 IU/m(2) every day for 10 days during multiagent induction therapy. Of these patients, 13 received i.v. therapy a nd 16 received i.m. therapy. During the reinduction phase the patients rece ived Erwinia ASNase 30,000 IU/m(2) twice a week for 2 weeks (Mondays and Th ursdays) (8 patients in the i.v.-treated group and I I patients in the i.m. -treated group). ASNase activity (spectrophotometric assay I) was measured in plasma samples obtained from the patients at various times during therap y. Results: The estimated half-life was 6.4 +/- 0.5 h (n = 13), the absorpt ion rate after i.m. administration was found to limit elimination. The appa rent volume of distribution corresponded well with the volume of plasma. Th e estimated clearance suggested that Erwinia ASNase is a low-clearance drug . Bioavailability after i.m. administration was (mean +/- SEM) 27.0 +/- 4.5 % (range 11-61 %; n = 12). Conclusions: In this study the pharmacokinetic parameters after i.v. and i.m. administration of Erwinia ASNase were determ ined based on a substantial number of patients. The present findings emphas ize the importance of conducting proper pharmacokinetic studies before a ne w drug or a new preparation of a drug is introduced in a different schedule .