RESUMO
Alkylating agents are widely used in high-dose chemotherapy regimens in combination with hematological support. Knowledge about the pharmacokinetics and pharmacodynamics of these agents administered in high doses is critical for the safe and efficient use of these regimens. The aim of this review is to summarize the clinical pharmacology of the alkylating agents (including the platinum compounds) in high-dose chemotherapy. Differences between conventional and high doses will be discussed.
Assuntos
Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/farmacocinética , Alcanossulfonatos/administração & dosagem , Alcanossulfonatos/efeitos adversos , Alcanossulfonatos/farmacocinética , Alcanossulfonatos/farmacologia , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Aziridinas/administração & dosagem , Aziridinas/efeitos adversos , Aziridinas/farmacocinética , Aziridinas/farmacologia , Humanos , Compostos de Mostarda Nitrogenada/administração & dosagem , Compostos de Mostarda Nitrogenada/efeitos adversos , Compostos de Mostarda Nitrogenada/farmacocinética , Compostos de Mostarda Nitrogenada/farmacologia , Compostos de Nitrosoureia/administração & dosagem , Compostos de Nitrosoureia/efeitos adversos , Compostos de Nitrosoureia/farmacocinética , Compostos de Nitrosoureia/farmacologia , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/farmacocinética , Compostos Organoplatínicos/farmacologia , Triazenos/administração & dosagem , Triazenos/efeitos adversos , Triazenos/farmacocinética , Triazenos/farmacologiaRESUMO
An assay for the simultaneous quantitative determination of thioTEPA, TEPA and the recently identified metabolite N,N'-diethylene-N"-2-chloroethylphosphoramide (monochloroTEPA) in human urine has been developed. MonochloroTEPA was synthesized by incubation of TEPA with sodium chloride at pH 8. Thus, with this assay monochloroTEPA is quantified as TEPA equivalents. Analysis of the three analytes in urine was performed using gas chromatography with selective nitrogen-phosphorous detection after extraction with a mixture of 1-propanol and chloroform from urine samples. Diphenylamine was used as internal standard. Recoveries ranged between 70 and 100% and both accuracy and precision were less than 15%. Linearity was accomplished in the range of 25-2500 ng/ml for monochloroTEPA and 25-5000 ng/ml for thioTEPA and TEPA. MonochloroTEPA proved to be stable in urine for at least 4 weeks at -80 degrees C. ThioTEPA, TEPA and monochloroTEPA cummulative urinary excretion from two patients treated with thioTEPA are presented demonstrating the applicability of the assay for clinical samples and that the excreted amount of monochloroTEPA exceeded that of thioTEPA on day 2 to 5 of urine collection.