Vincristine pharmacokinetics after repetitive dosing in children
| Autor: | C.J. Meeuwsen-de Boer, Pauline Koopmans, Donald R. A. Uges, Corrie Gidding, Willem Kamps, S.S.N. de Graaf |
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| Rok vydání: | 1999 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Vincristine Behandelingsresultaten bij kinderen met solide tumoren Toxicology Wilms Tumor Drug Administration Schedule Treatment of children with solid tumors Pharmacokinetics Internal medicine Acute lymphocytic leukemia Medicine Humans Pharmacology (medical) Child Chromatography High Pressure Liquid Pharmacology Volume of distribution business.industry Lymphoma Non-Hodgkin Wilms' tumor Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Pediatric cancer Antineoplastic Agents Phytogenic Vinblastine Area Under Curve Immunology Analysis of variance business medicine.drug Half-Life |
| Zdroj: | Cancer Chemotherapy and Pharmacology, 44, 203-209 Cancer Chemotherapy and Pharmacology, 44, pp. 203-209 |
| ISSN: | 0344-5704 |
| Popis: | Purpose: We studied vincristine disposition after 169 weekly i.v. bolus injections in 32 children with acute lymphoblastic leukemia, non-Hodgkin lymphoma, or Wilms' tumor. The aim of the study was to determine intrapatient and interpatient variability in vincristine disposition and demographic, clinical, and biochemical characteristics influencing this variability. Methods: Vincristine plasma concentrations were measured by a high-performance liquid chromatography assay with electrochemical detection. A limited sampling strategy was used based on a bayesian parameter estimation algorithm that is part of the ADAPT II software package. A two-compartment, first-order model was fitted to the data, and pharmacokinetic parameters were calculated from the model using the ADAPT II software. For statistical analysis, analysis of variance (ANOVA), t test, simple and multiple regression analysis, and non-parametric or robust equivalents were used. Results: Results showed a large intrapatient and interpatient variability in distribution half-life, elimination half-life, total body clearance, apparent volume of distribution at steady state, and area under the concentration-time curve. Intrapatient variability was significantly smaller than interpatient variability for all these parameters except distribution half-life. The diagnosis or treatment protocol turned out to be the most predictive characteristic; leukemia and non-Hodgkin lymphoma patients had a significantly higher total body clearance than Wilms' tumor patients. Conclusions: We conclude that both intrapatient and interpatient variability in vincristine pharmacokinetics is large in pediatric cancer patients and that variability, although significantly influenced by diagnosis, largely remains unpredictable. |
| Databáze: | OpenAIRE |
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