Metodología analítica de determinación de antineoplásicos de interés clínico. Aplicación a estudios farmacocinéticos

Resumen

TITULO: METODOLOGÍA ANALÍTICA DE DETERMINACIÓN DE ANTINEOPLASICOS DE INTERÉS CLÍNICO. APLICACIÓN A ESTUDIOS FARMACOCINETICOS RESUMEN: ANALYTICAL METHODS FOR DETERMINATION OF CLINICAL INTEREST ANTINEOPLASICS. Application to pharmacokinetic studies. Cancer can seriously threaten human health and it is a leading cause of death. A worthy goal, at the present, is to develop treatments that produce remission and/or palliation. Chemotherapy for cancer is understood in a narrower sense of using chemotherapeutical agents directed at killing or controlling the cancer cells, and the cancer chemotherapeutic agents are often toxic or even life-threatening. It carries a high risk due to drug toxicity. Problems still exist even for successful chemotherapy, and the patients have to tolerate severe is de effects and sacrifice their quality of life. Cancer chemotherapy could be improved by the application of Therapeutic Drug monitoring since this kind of drugs have highly variable pharmacokinetics and narrow therapeutic Indices. Maximal efficacy of cancer chemotherapy is of prime importance because of the enormous consequences to cancer patients. Knowledge about the therapeutic range of antineoplasics is of great el inical utility in order to maximize efficacy and minims se undesirable adverse effects. Boding surface area (BSA) has been routinely employed in the el inical trials to dose antineoplasic agents; in the last years, however, several studies have shown that BSA fail in anticancer agents which suffer hepatic metabolism. The alternative strategy when BSA has proven to be useless is to individual use the dose according to pharmacokinetic parameters. During last year¿s some studies have been done with antineoplastic agents, for analysing relationships between the pharmacokinetic of the drug and, therapeutic and toxic effects related to its administration. Their results have made use of increasing therapeutic benefits in these patients (disease free survival, survival, increasing of quality of life, decreasing of adverse effects,...) . Selective and sensitive analytical methods for the quantitative evaluation of drugs and their metabolites are critical for the successful of el inical pharmacokinetics studies. So, the first step in this work will be the development of the analytical methods for the determination of antineoplasic levies in human plasma or tissue (carboplatin, tegafur, capecitabine, irinotecan, docetaxel and paclitaxel) with the study of the analytical parameters (selectivity, linearity and range, within and between day precision, aecuracy, detection and quantificatión limits, recovery and stability) to ensure suitable performance of the analytical method and reliable and reproducible results for the intended use. The chromatographic methods presented in this research work have been carried out in the pharmacokinetic laboratory of the universitary Hospital of Navarra. They have been validated for pharmacokinetic evaluation and therapeutic monitoring of these agents in the el inical setting, according to the fda Guidance for Industry which provides general recommendations for Bioanalitical Method validation.