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Cancer Chemother Pharmacol ; 62(4): 679-83, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18084764

RESUMEN

OBJECTIVE: To evaluate the pharmacokinetic inter-patient variability of 30-min hyperthermic intraperitoneal oxaliplatin chemotherapy. PATIENTS AND METHODS: Data were obtained from 24 patients who were treated according to two procedures of heated intra-operative intraperitoneal oxaliplatin. For the first procedure (12 patients), the solution instilled within the peritoneal cavity contained oxaliplatin, and a delay of 8-10 min was necessary to reach a temperature of 42-43 degrees C. For the second procedure (12 patients), the cavity was initially filled only with the dextrose solution, and oxaliplatin was added to the peritoneal instillate when temperature reached 42-43 degrees C. Plasma and peritoneal fluid oxaliplatin concentrations were analyzed according to a population pharmacokinetic approach using NONMEM. RESULTS: Peritoneal and total plasma data were simultaneously analyzed according to a three-compartment pharmacokinetic model. The peritoneal half-life ranged between 18 and 42 min. The mean peritoneal clearance was 5.47 L/h (+/-21%), and the mean plasma clearance was 3.71 L/h (+/-47%). The heated intra-operative procedure did not have any impact on oxaliplatin pharmacokinetics. CONCLUSION: The inter-individual variability was larger for plasma pharmacokinetic parameters than that for peritoneal parameters. However, the percentage of oxaliplatin dose absorbed during a 30-min hyperthermic intraperitoneal chemotherapy may vary from 40 to 68%. The present pharmacokinetic model will be useful to implement pharmacokinetic evaluation of further clinical trials of hyperthermic intraperitoneal chemotherapy based on platinum compounds' administration.


Asunto(s)
Antineoplásicos/farmacocinética , Hipertermia Inducida , Neoplasias/metabolismo , Compuestos Organoplatinos/farmacocinética , Piridinas/farmacocinética , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Líquido Ascítico/química , Cromatografía Líquida de Alta Presión , Terapia Combinada , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas , Femenino , Humanos , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Piridinas/administración & dosificación , Piridinas/efectos adversos
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