Linked Life Data

15496649

Source:http://linkedlifedata.com/resource/pubmed/id/15496649

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pubmed-article:15496649pubmed:issue11lld:pubmed
pubmed-article:15496649pubmed:dateCreated2004-10-21lld:pubmed
pubmed-article:15496649pubmed:abstractTextThe 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.lld:pubmed
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pubmed-article:15496649pubmed:dateRevised2007-11-15lld:pubmed
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pubmed-article:15496649pubmed:articleTitlePopulation pharmacokinetics of clofarabine, a second-generation nucleoside analog, in pediatric patients with acute leukemia.lld:pubmed
pubmed-article:15496649pubmed:affiliationILEX Products, 4545 Horizon Hill Boulevard, San Antonio, TX 78229, USA.lld:pubmed
pubmed-article:15496649pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:15496649pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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