Abstract
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.
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We thank Miss Tracy Chapman for editorial assistance with the English.
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Ferron, G., Dattez, S., Gladieff, L. et al. Pharmacokinetics of heated intraperitoneal oxaliplatin. Cancer Chemother Pharmacol 62, 679–683 (2008). https://doi.org/10.1007/s00280-007-0654-x
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DOI: https://doi.org/10.1007/s00280-007-0654-x