title: Population pharmacokinetics and pharmacodynamics of cisplatinum during hyperthermic intraperitoneal chemotherapy using a closed abdominal procedure.
abstract: The aim of this work was to study the pharmacokinetics of cisplatinum during closed abdominal hyperthermic intraperitoneal chemotherapy (HIPEC) using a population pharmacokinetics approach. Forty patients were treated between January 2003 and December 2004. Peritoneal and blood concentrations of cisplatinum were used to develop a pharmacokinetic model of the peritoneal and plasma compartments using NONMEM software. Different covariables were analyzed to identify those that explain part of the interindividual variability of the pharmacokinetic parameters. Relationships between the area under the concentration-time curve (AUC) and hematological and renal toxicity and efficiency were explored. The pharmacokinetics of cisplatinum were modeled with a 3-compartment model. Estimations of the plasma and peritoneal pharmacokinetic parameters were obtained. No clinical or biological covariates correlated with these parameters. No direct relationship between the AUC of the peritoneal or plasma and toxicity or efficiency was demonstrated. The pharmacokinetics during HIPEC could be modeled with a 3-compartment model using a population pharmacokinetics approach. This work is the basis of further studies. Notably, studies including new patients will analyze the impact of abdominal cavity volume and the variation of the abdominal pressure during HIPEC on the pharmacokinetics of cisplatinum.
authors.affiliation: Department of Digestive Surgery, Centre Hospitalo-Universitaire Lyon Sud, Pierre Bénite cedex, France. eddy.cotte@chu-lyon.fr
authors.forename: Eddy
authors.initials: E
authors.lastname: Cotte
authors.forename: Olivier
authors.initials: O
authors.lastname: Colomban
authors.forename: Jérome
authors.initials: J
authors.lastname: Guitton
authors.forename: Brigitte
authors.initials: B
authors.lastname: Tranchand
authors.forename: Nawel
authors.initials: N
authors.lastname: Bakrin
authors.forename: François-Noël
authors.initials: FN
authors.lastname: Gilly
authors.forename: Olivier
authors.initials: O
authors.lastname: Glehen
authors.forename: Michel
authors.initials: M
authors.lastname: Tod
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D008954:Models, Biological; D017711:Nonlinear Dynamics; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D016685:Mitomycin; D002945:Cisplatin