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Pharmacodynamic Modeling of Vincristine in Lymphoma Patients  

Seo, Jeong-Won (New Drug Research Team, National Institute of Food and Drug Safety Evaluation (NIFDA))
Kim, Dong-Hyun (College of Pharmacy, Chungnam National University)
Yun, Jin-Sang (Chungnam National University Hospital)
Kim, Seon-Hwa (Division of Pharmacological Reserch, National institute of Food and Drug Evaluation, Korea Food & Drug Evaluation)
Choi, Bo-Yoon (College of Pharmacy, Seoul National University)
Oh, Jung-Mi (College of Pharmacy, Seoul National University)
Kwon, Kwang-Il (College of Pharmacy, Chungnam National University)
Publication Information
Korean Journal of Clinical Pharmacy / v.21, no.2, 2011 , pp. 145-155 More about this Journal
Abstract
The objective of this study was to determine whether any pretreatment parameters were associated with pharmacological effect or toxicity parameters after vincristine administration and to describe a mathematical model, which explains the interpatient pharmacodynamic variability. The relationship between patient characteristics and vincristine dose and hematological toxicity were evaluated. 68 pediatric and adolescence patients and 107 adults with acute lymphoblastic leukemia were treated with vincristine $1.5mg/m^2/day$ IV and other anticancer drugs as scheduled. Complete blood counts and other blood test results were obtained. The input variables were age, gender, weight, lean body weight (LBW), height, body surface area, vincristine dose and total vincristine dose. The outcome measures were nadir values (white blood cells, absolute neutrophil counts, hemoglobin, and platelets); the absolute decrease, relative decrease, and survival fraction of blood cells. Polynomial regression analysis was carried out to determine the other significant covariates. The variability of $WBC_{nadir}$ was modeled with good precision and accuracy with a two-covariate model. This model should be validated and improved on with further clinical data. We believe that such pharmacodynamic modeling should be explored further to determine its performance and clinical relevance compared with modeling using pharmacokinetic parameter.
Keywords
vincristine; pharmacodynamic model; lymphoma;
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Times Cited By KSCI : 2  (Citation Analysis)
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