PMID- 19741605
OWN - NLM
STAT- MEDLINE
DCOM- 20091215
LR  - 20220330
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Print)
IS  - 0009-9236 (Linking)
VI  - 86
IP  - 6
DP  - 2009 Dec
TI  - Comparison of native E. coli and PEG asparaginase pharmacokinetics and 
      pharmacodynamics in pediatric acute lymphoblastic leukemia.
PG  - 651-8
LID - 10.1038/clpt.2009.162 [doi]
AB  - Asparaginase (ASP) is used routinely in frontline clinical trials for the 
      treatment of childhood acute lymphoblastic leukemia (ALL). The goals of this 
      study were to assess the pharmacokinetics and pharmacodynamics of ASP and to 
      mathematically model the dynamics between ASP and asparagine (ASN) in relapsed 
      ALL. Forty children were randomized to receive either native or polyethylene 
      glycolated (PEG) Escherichia coli ASP during reinduction therapy. Serial plasma 
      ASP and ASN, cerebrospinal fluid (CSF) ASN, and serum anti-ASP antibody samples 
      were collected. The ASP clearance was higher (P = 0.001) for native vs. PEG ASP. 
      Patients with antibodies to PEG ASP had faster PEG ASP clearance (P = 0.004) than 
      did antibody-negative patients. Patients who were positive for antibodies had 
      higher CSF ASN concentrations than did those who were negative (P = 0.04). The 
      modeling suggests that by modifying dosages, comparable ASN depletion is 
      achievable with both preparations. At relapse, there were significant 
      pharmacokinetic and pharmacodynamic differences attributable to ASP preparation 
      and antibody status.
FAU - Panetta, J C
AU  - Panetta JC
AD  - Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, 
      Memphis, Tennessee, USA.
FAU - Gajjar, A
AU  - Gajjar A
FAU - Hijiya, N
AU  - Hijiya N
FAU - Hak, L J
AU  - Hak LJ
FAU - Cheng, C
AU  - Cheng C
FAU - Liu, W
AU  - Liu W
FAU - Pui, C H
AU  - Pui CH
FAU - Relling, M V
AU  - Relling MV
LA  - eng
GR  - R01 CA051001-15/CA/NCI NIH HHS/United States
GR  - CA 51001/CA/NCI NIH HHS/United States
GR  - P30 CA021765/CA/NCI NIH HHS/United States
GR  - P30 CA021765-31/CA/NCI NIH HHS/United States
GR  - R01 CA051001/CA/NCI NIH HHS/United States
GR  - CA 21765/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090909
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Antibodies)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Recombinant Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 7006-34-0 (Asparagine)
RN  - 7D96IR0PPM (pegaspargase)
RN  - EC 3.5.1.1 (Asparaginase)
SB  - IM
MH  - Antibodies/blood
MH  - Antineoplastic Agents/immunology/*pharmacokinetics/*therapeutic use
MH  - Asparaginase/biosynthesis/genetics/immunology/*pharmacokinetics/*therapeutic use
MH  - Asparagine/blood/cerebrospinal fluid
MH  - Computer Simulation
MH  - Escherichia coli/*enzymology/genetics
MH  - Humans
MH  - Models, Biological
MH  - Polyethylene Glycols/*pharmacokinetics/*therapeutic use
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug 
      therapy/immunology/metabolism
MH  - Recombinant Proteins/pharmacokinetics/therapeutic use
MH  - Recurrence
MH  - Treatment Failure
PMC - PMC2831746
MID - NIHMS175482
COIS- Conflict-of-interest disclosure: The authors declare no competing financial 
      interests.
EDAT- 2009/09/11 06:00
MHDA- 2009/12/16 06:00
PMCR- 2010/12/01
CRDT- 2009/09/11 06:00
PHST- 2009/09/11 06:00 [entrez]
PHST- 2009/09/11 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - clpt2009162 [pii]
AID - 10.1038/clpt.2009.162 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2009 Dec;86(6):651-8. doi: 10.1038/clpt.2009.162. Epub 2009 
      Sep 9.