Document Detail


Population pharmacokinetics of hyperthermic intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis after cytoreductive surgery.
MedLine Citation:
PMID:  23274396     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: To characterize the hyperthermic intraperitoneal oxaliplatin (HIO) pharmacokinetics in peritoneum and plasma in patients with peritoneal carcinomatosis (PC) after cytoreductive surgery (CRS). METHODS: Data from 36 patients receiving HIO diluted in isotonic 4 % icodextrin were combined with data from 13 patients receiving HIO diluted in isotonic 5 % dextrose. Total oxaliplatin in peritoneal and plasma fluids were used to characterize an open two-compartment disposition model with linear distribution and elimination and first-order absorption from peritoneum to plasma using NONMEM software. The effect of patient- and treatment-related covariates on oxaliplatin pharmacokinetic parameters was explored. RESULTS: The typical value (interindividual variability, %) in k ( a ), CL, and V ( ss ) were 0.57 h(-1) (43 %), 1.71 L h(-1) (39 %), and 77 L (65 %), respectively. No significant effect of age, body surface area, sex, creatinine clearance, liver metastases, PC index, and complete cytoreduction on pharmacokinetic parameters was found. A 12-15 % reduction in peritoneal volume of distribution was observed in patients receiving HIO diluted in 5 % dextrose relative to those patients receiving HIO diluted in 4 % icodextrin. CONCLUSIONS: The integration of peritoneal and plasma data demonstrated oxaliplatin linear absorption from peritoneum to plasma, non-specific distribution to a peripheral compartment, and linear elimination from the central compartment when HIO was administered with isotonic carrier solutions to PC patients who underwent CRS. Only the effect of the carrier solution had an impact in the peritoneal volume of distribution, but its clinical relevance seems to be limited, especially for short HIO infusions (<60 min).
Authors:
Carlos Pérez-Ruixo; Belén Valenzuela; José Esteban Peris; Pedro Bretcha-Boix; Vanesa Escudero-Ortiz; José Farré-Alegre; Juan José Pérez-Ruixo
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-30
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  -     ISSN:  1432-0843     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Pharmacy and Pharmaceutical Technology Department, University of Valencia, Valencia, Spain.
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