[Research on the pharmacokinetics and pharmacodynamics of L-asparaginase during its treatment of childhood acute lymphoblastic leukemia].
OBJECTIVE
To investigate the changes in the activity of Escherichia coli asparaginase (L-asp) and the concentration of asparagines (ASN) in the plasma of the acute lymphoblastic leukemia (ALL) children receiving L-asp containing chemotherapeutic protocol to explore more reasonable usage of L-asp in the treatment of childhood ALL.


METHODS
L-asp containing hemotherapy regimen of VDLP was used, in which L-asp (10,000 U/m(2)) was administered intravenously every other day for 10 doses in 15 children with ALL. A total of 340 peripheral blood samples were collected at scheduled time points during the therapy and plasma L-asp activity (by spectrophotometric assay) and asparagines concentration (by RP-HPLC) were measured.


RESULTS
During the administration of L-asp, the plasma L-asp activity was increasing gradually peaked after eight doses and then decreased gradually, while the plasma concentration of asparagines maintained in complete or nearly complete depletion status. After the therapy courses finished, a plasma L-asp activity above 100 U/L with asparagines almost complete depletion status was lasting for about seven days.


CONCLUSIONS
The current L-asp containing chemotherapeutic protocols in which L-asp was administered in a dose of 10 000/m(2) intravenously every other day, are efficient enough for the depletion of plasma ASN.
Chen
Fu-xiong
FX
Department of Pediatrics, the First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120, China.
Cui
Yan-qin
YQ
Wu
Zi-liang
ZL
Ye
Tie-zhen
TZ
Lai
Yong-hong
YH
Zou
Ya-wei
YW
Lu
Cheng-yu
CY
Guan
Jing-ming
JM
Wei
Feng-gui
FG
Zhang
Hui
H
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001216:Asparagine / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
D001216:Asparagine; D001215:Asparaginase