Source:http://linkedlifedata.com/resource/pubmed/id/15496649
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2004-10-21
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| pubmed:abstractText |
The population pharmacokinetics of plasma clofarabine and intracellular clofarabine triphosphate were characterized in pediatric patients with acute leukemias. Traditional model-building techniques with NONMEM were used. Covariates were entered into the base model using a forward selection significance level of .05 and a backwards deletion criterion of .005. Model performance, stability, and influence analysis were assessed using the nonparametric bootstrap and n-1 jackknife. Simulations were used to understand the relationship between important covariates and exposure. A 2-compartment model with weight (scaled to a 40-kg reference patient) modeled as a power function on all pharmacokinetic parameters (0.75 on clearance-related terms and 1.0 on volume-related terms) was fit to plasma clofarabine concentrations (n = 32). White blood cell (WBC) count, modeled as a power function (scaled to a WBC count of 10 x 10(3)/microL), was a significant predictor of central volume with power term 0.128 +/- 0.0314. A reference patient had a systemic clearance of 32.8 L/h (27% between-subject variability [BSV]), a central volume of 115 L (56% BSV), an intercompartmental clearance of 20.5 L/h (27% BSV), and a peripheral volume of 94.5 L (39% BSV). Intracellular clofarabine triphosphate concentrations were modeled using a random intercept model without any covariates. The average predicted concentration was 11.6 +/- 2.62 microM (80% BSV), and although clofarabine triphosphate half-life could not be definitively estimated, its value was taken to be longer than 24 hours. The results confirm that clofarabine should continue being dosed on a per-squaremeter or per-body-weight basis.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
|
| pubmed:issn |
0091-2700
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| pubmed:author |
pubmed-author:BonatePeter LPL,
pubmed-author:CraigAdamA,
pubmed-author:GandhiVarshaV,
pubmed-author:GaynonPaulP,
pubmed-author:JehaSimaS,
pubmed-author:KadotaRichardR,
pubmed-author:LamGilbert NGN,
pubmed-author:PlunkettWilliamW,
pubmed-author:RazzoukBassemB,
pubmed-author:RyttingMichaelM,
pubmed-author:SteinherzPeterP,
pubmed-author:WeitmanSteveS
|
| pubmed:issnType |
Print
|
| pubmed:volume |
44
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1309-22
|
| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:15496649-Adenine Nucleotides,
pubmed-meshheading:15496649-Adolescent,
pubmed-meshheading:15496649-Adult,
pubmed-meshheading:15496649-Arabinonucleosides,
pubmed-meshheading:15496649-Child,
pubmed-meshheading:15496649-Child, Preschool,
pubmed-meshheading:15496649-Clinical Trials, Phase I as Topic,
pubmed-meshheading:15496649-Clinical Trials, Phase II as Topic,
pubmed-meshheading:15496649-Computer Simulation,
pubmed-meshheading:15496649-Half-Life,
pubmed-meshheading:15496649-Humans,
pubmed-meshheading:15496649-Leukemia, Myeloid, Acute,
pubmed-meshheading:15496649-Leukocyte Count,
pubmed-meshheading:15496649-Metabolic Clearance Rate,
pubmed-meshheading:15496649-Models, Biological,
pubmed-meshheading:15496649-Precursor Cell Lymphoblastic Leukemia-Lymphoma,
pubmed-meshheading:15496649-Reproducibility of Results
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| pubmed:year |
2004
|
| pubmed:articleTitle |
Population pharmacokinetics of clofarabine, a second-generation nucleoside analog, in pediatric patients with acute leukemia.
|
| pubmed:affiliation |
ILEX Products, 4545 Horizon Hill Boulevard, San Antonio, TX 78229, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|