Pharmacokinetics of heated intraperitoneal oxaliplatin

• Published in: Cancer chemotherapy and pharmacology 2008-09, Vol.62 (4), p.679-683
• Main Authors: Ferron, G., Dattez, S., Gladieff, L., Delord, J.-P., Pierre, S., Lafont, T., Lochon, I., Chatelut, E.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Ascitic Fluid - chemistry; Biological and medical sciences; Cancer Research; Chromatography, High Pressure Liquid; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Hyperthermia, Induced; Infusions, Parenteral; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Neoplasms - drug therapy; Neoplasms - metabolism; Oncology; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; Organoplatinum Compounds - pharmacokinetics; Original Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pyridines - administration & dosage; Pyridines - adverse effects; Pyridines - pharmacokinetics
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-007-0654-x

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°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°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.