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Pharmacodynamics of High-Dose Chemotherapy

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There is usually considerable variability in anticancer drug plasma levels when delivered at high doses requiring stem-cell support. Given their narrow therapeutic windows and wide interpatient pharmacokinetic variability, drug monitoring and pharmacokinetic-directed dosing represent an attractive strategy in this setting. A major previous requirement to successful application of therapeutic drug monitoring is identification of a significant and clinically meaningful pharmacodynamic correlation between a pharmacokinetic parameter and a toxic or therapeutic outcome, or preferably, both. In this review, we will analyze the current knowledge of identified pharmacodynamic correlations in high-dose chemotherapy. We will summarize the observations from other authors and our own, on drugs employed at high doses, such as cyclophosphamide, melphalan, busulfan, carmustine, paclitaxel, or docetaxel.
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Keywords: Pharmacodynamics High-Dose Chemotherapy; anticancer drug plasma levels; busulfan; carmustine; cyclophosphamide; docetaxel; melphalan; paclitaxel

Document Type: Review Article

Publication date: March 1, 2001

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  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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