Pharmacokinetics of vincristine in children and adolescents with acute lymphocytic leukemia
We studied the pharmacokinetics of vincristine in children with acute lymphocytic leukemia by means of a specific high-performance liquid chromatographic assay with ultraviolet and electrochemical detection and a limited sampling strategy. Our objectives were to characterize the disposition of vincristine in pediatric patients, to determine clinical, demographic, or biochemical variables related to variability in vincristine pharmacokinetic parameters, and to assess the relationship between pharmacokinetic parameters and vincristine neurotoxicity. Plasma samples were collected at 5 and 30 minutes, and 1, 3, and 24 hours after a rapid intravenous injection during 3 minutes. Vincristine-induced neurotoxicity was retrospectively evaluated by chart review. Pharmacokinetic studies were completed for 64 doses in 54 children between 2 months and 18 years of age (median, 4.3 years), including 2-month-old monozygous twin girls. Vincristine clearance, estimated by Bayesian methods, was highly variable, with a mean (SD) clearance of 19.9 (14.9) ml/min per kilogram or 482 (342) ml/min per square meter. Mean clearance for all subjects was faster than in published studies of adults, which may be related in part to the greater specificity of ...Continue Reading
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