A limited-sampling strategy for estimation of etoposide pharmacokinetics in cancer patients
| Autor: | Athanassios Iliadis, Isabelle Lochon, Pierre Canal, Gilles Freyer, Brigitte Tranchand, Véronique Trillet-Lenoir, Blandine Ligneau, C. Ardiet, Carole Amsellem, Etienne Chatelut |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Male Cancer Research Metabolic Clearance Rate medicine.medical_treatment Hematologic toxicity Pharmacology Toxicology Models Biological Pharmacokinetics Neoplasms medicine Limited sampling Humans Pharmacology (medical) Infusions Intravenous Etoposide Selection Bias Aged Volume of distribution Aged 80 and over Chemotherapy Dose-Response Relationship Drug business.industry Cancer Reproducibility of Results Middle Aged medicine.disease Anticancer drug Antineoplastic Agents Phytogenic Oncology Female business medicine.drug Half-Life |
| Zdroj: | Cancer chemotherapy and pharmacology. 43(4) |
| ISSN: | 0344-5704 |
| Popis: | Etoposide (VP16), a widely used anticancer drug, is a topoisomerase II inhibitor. A number of studies have highlighted a correlation between hematologic toxicity and pharmacokinetic or physiological parameters. Other studies have also suggested that the anti-tumor response could be related to the plasma etoposide concentration. Therefore, it would seem of interest to individualize VP16 dose regimens on the basis of pharmacokinetic parameters. The aim of this study was to develop and validate a limited-sampling strategy allowing VP16 pharmacokinetic evaluation with minimal disturbance to the patient. A total of 34 patients (54 kinetics) received VP16 at various dose regimens, with doses ranging between 30 and 200 mg and infusion times varying between 0.5 and 2 h. The statistical characteristics of the pharmacokinetic parameters were assessed from the first courses of treatment performed in 23/34 patients; then the following three-sample protocol was designed: the end of the infusion and 5 and 24 h after the start of the infusion. For validation of the model the main pharmacokinetic parameters (clearance, half-lives, volume of distribution) were estimated in the 11 remaining patients by maximum-likelihood estimation (ML) and by Bayesian estimation (BE) using the three sampling times designed. Statistical comparison showed a good concordance between ML and BE estimates (the bias for clearance was –1.72%). The limited-sampling strategy presented herein can thus be used for accurate estimation of VP16 pharmacokinetic parameters. |
| Databáze: | OpenAIRE |
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