Pharmacokinetics of heated intraperitoneal oxaliplatin
To evaluate the pharmacokinetic inter-patient variability of 30-min hyperthermic intraperitoneal oxaliplatin chemotherapy. 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. 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. 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.