Comparison of intramuscular therapy with Erwinia asparaginase and asparaginase Medac:: pharmacokinetics, pharmacodynamics, formation of antibodies and influence on the coagulation system

被引:49
作者
Albertsen, BK
Schroder, H
Ingerslev, J
Jakobsen, P
Avramis, VI
Müller, HJ
Carlsen, NT
Schmiegelow, K
机构
[1] Aarhus Univ, Dept Pharmacol, DK-8000 Aarhus C, Denmark
[2] Aarhus Univ, Ctr Clin Pharmacol, DK-8000 Aarhus, Denmark
[3] Skejby Hosp, Dept Paediat Oncol, Aarhus, Denmark
[4] Skejby Hosp, Ctr Haemophilia & Thrombosis, Dept Clin Immunol, Aarhus, Denmark
[5] Univ So Calif, Childrens Hosp, Los Angeles, CA 90027 USA
[6] Univ Munster, Dept Paediat Haematol Oncol, D-4400 Munster, Germany
[7] Odense Hosp, Dept Paediat Oncol, Odense, Denmark
[8] Rigshosp, Dept Paediat Oncol, DK-2100 Copenhagen, Denmark
关键词
Erwinia ASNase; ASNase Medac; i.m; administration; pharmacokinetics; side-effects;
D O I
10.1046/j.1365-2141.2001.03148.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Asparaginase comes from different biological sources and the various preparations have different pharmacokinetic properties, and their tendency to induce side-effects is different. Erwinia asparaginase (ASNase) has a shorter half-life than the Escherichia colt preparations, and it has been reported to be less immunogenic than the E. coli preparations and to induce fewer coagulation disorders. Children with newly diagnosed acute lymphoblastic leukaemia (ALL) were included in this study. Twenty-seven patients were treated with Erwinia ASNase (induction therapy 30,000 IU/m(2)/d i.m. for 10 d, and re-induction therapy 30.000 IU/m(2) twice a week for 2 weeks) and 15 were treated with ASNase Medac (induction therapy 1.000,IU/m(2)/d i.m. for 10 d, and re-induction therapy 5.000 IU/m(2) i.m. twice a week for 2 weeks). Blood samples were drawn to determine enzyme activity, L-asparagine, antiasparaginase antibodies, and coagulation parameters. After i.m. administration, Erwinia ASNase displayed a protracted absorption phase compared to ASNase Medac. The mean bioavailability after i.m. administration was 27% for Erwinia ASNase and 45% for ASNase Medac respectively. Mean trough enzyme activities during induction therapy were Erwinia ASNase 1748 IU/l and ASNase Medac 272 IU/l, and during re-induction therapy Erwinia ASNase 83 IU/l and ASNase Medac 147 IU/l. We conclude that in this setting, therapy with ASNase Medac resulted in sufficient treatment during both phases of therapy, whereas treatment with Erwinia ASNase resulted in unnecessarily intense therapy during the induction phase and insufficient treatment during the re-induction phase. There was no significant difference in the incidence of antibody formation, and therapy with Erwinia ASNase resulted in a more pronounced influence on the coagulation parameters than therapy with ASNase Medac.
引用
收藏
页码:983 / 990
页数:8
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