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


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 degrees 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 degrees 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.


CONCLUSIONS
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.
Ferron
G
G
Department of Surgical Oncology and Anesthaesiology, Institut Claudius-Regaud, Toulouse, France.
Dattez
S
S
Gladieff
L
L
Delord
J-P
JP
Pierre
S
S
Lafont
T
T
Lochon
I
I
Chatelut
E
E
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001202:Ascitic Fluid / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011725:Pyridines; C431073:oxiplatin