The pharmacokinetics, pharmacodynamics, efficacy, and safety of a new recombinant Escherichia coli-asparaginase preparation was compared with Asparaginase medac. Thirty-two children with acute lymphoblastic leukemia were randomized to receive one of both agents at a dose of 5000 U/m 2 every 3 days, for a total of 8 doses during induction treatment. The serum activity-time profile after the first dose of recombinant asparaginase was similar to that of Asparaginase medac. The trough serum activities were greater than the desired threshold of 100 U/L in both treatment groups. Asparagine was completely depleted in serum and in cerebrospinal fluid, whereas glutamine levels were only moderately influenced. No significant difference between the 2 treatments regarding the degree of asparagine depletion, duration of depletion, complete remission rate, and minimal residual disease status at the end of induction, overall frequency or intensity of adverse events was seen. Observed adverse reactions are known as possible and la-

The main aim of this analysis was to characterize the population pharmacokinetics of native Escherichia coli asparaginase (ASNase medac) in pediatric patients with previously untreated acute lymphoblastic leukemia. Secondary objective was to give further evidence for bioequivalence between ASNase medac and a new recombinant ASNase preparation. The authors reanalyzed 233 plasma samples from 16 children treated according to the DCOG-ALL 10 protocol (5000 U/m(2) ASNase medac) using NONMEM. Subsequently, assessment of bioequivalence was performed by including the preparation as a categorical covariate into the PopPK model when analyzing data of both preparations (480 samples, 32 children). A linear 2-compartment model with first-order elimination sufficiently described ASNase medac pharmacokinetics. The parameters found were as follows: total body clearance 0.13 L/h ± 12.4% per 1.73 m(2), volume of distribution in the central compartment 4.11 L ± 12.3% per 70 kg, volume of distribution in the peripheral compartment 1.63 L per 70 kg and intercompartmental clearance 0.106 L/h (mean ± interindividual variability). A visual predictive check procedure and simulation of different dosages ASNase medac administered in the ALL-BFM protocol indicated adequate model performance. Assessment of bioequivalence provided a difference of about 14% in clearance of both preparations being too small to be considered as clinically relevant. A population pharmacokinetic model of ASNase medac in pediatric patients with previously untreated acute lymphoblastic leukemia was established. The model was able to describe asparaginase activity of different dosages in the ALL-BFM protocol and provides further evidence for bioequivalence between ASNase medac and a new recombinant asparaginase preparation.