Pharmacokinetics of Erwinia asparaginase after intravenous and intramuscular administration.
OBJECTIVE
To describe the pharmacokinetics of Erwinia asparaginase (ASNase) after intravenous (i.v.) and intramuscular (i.m.) administration.


METHODS
A group of 29 children with newly diagnosed acute lymphoblastic leukemia (ALL) received Erwinia ASNase 30,000 IU/m2 every day for 10 days during multiagent induction therapy. Of these patients. 13 received i.v. therapy and 16 received i.m. therapy. During the reinduction phase the patients received Erwinia ASNase 30,000 IU/m2 twice a week for 2 weeks (Mondays and Thursdays) (8 patients in the i.v.-treated group and 11 patients in the i.m.-treated group). ASNase activity (spectrophotometric assay) was measured in plasma samples obtained from the patients at various times during therapy.


RESULTS
The estimated half-life was 6.4 +/- 0.5 h (n = 13), the absorption rate after i.m. administration was found to limit elimination. The apparent volume of distribution corresponded well with the volume of plasma. The 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 determined based on a substantial number of patients. The present findings emphasize the importance of conducting proper pharmacokinetic studies before a new drug or a new preparation of a drug is introduced in a different schedule.
Albertsen
B K
BK
Department of Pharmacology, University of Aarhus, Denmark. bka@farm.au.dk
Jakobsen
P
P
Schrøder
H
H
Schmiegelow
K
K
Carlsen
N T
NT
D000293:Adolescent; D001215:Asparaginase / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004885:Erwinia / Q000201:enzymology*; D006207:Half-Life; D006801:Humans; D007223:Infant; D007273:Injections, Intramuscular; D007275:Injections, Intravenous
D001215:Asparaginase