title: Pharmacokinetics of carboplatin after intraperitoneal administration.
abstract: The pharmacokinetics of carboplatin, ultrafilterable platinum, and total platinum after intraperitoneal (i.p.) administration were studied in peritoneal fluid, plasma, red blood cells (RBCs), and urine during a phase-I trial in patients with minimal, residual ovarian cancer. Samples were collected from 7 patients who had received carboplatin (200-500 mg/m2) in 21 dialysis fluid. The fluid was withdrawn after a 4-h dwell. Platinum concentrations were measured by flameless atomic absorption spectrometry, and intact carboplatin was determined by HPLC with electrochemical detection. Peak concentrations of carboplatin in plasma were obtained 2 h after the end of instillation. The mean ratio of peak concentrations of carboplatin in instilled fluid and plasma was 24 +/- 11. The peritoneal clearance of carboplatin was 8 +/- 3 ml/min, which was 12 times less than the plasma clearance (93 +/- 32 ml/min). Due to this clearance ratio, the AUCs for the peritoneal cavity were about 10 times higher than those for plasma. On average, 34% +/- 14% of the dose was still present in the instillation fluid that had been withdrawn after a dwell time of 4 h. In plasma, the mean value of AUC/Dnet (Dnet = Dose - amount recovered from the peritoneal cavity) after i.p. administration was comparable with that of AUC/D after i.v. administration. This means that unrecovered carboplatin (66%) was completely absorbed from the peritoneal cavity. It may be expected from this bioavailability that the maximum tolerated dose (MTD) of i.p.-administered carboplatin with a 4-h dwell is around 1.5 times higher than that after i.v. administration. Overall pharmacokinetic parameters of carboplatin and platinum in plasma were comparable after i.p. and i.v. administration.
authors.affiliation: Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Elferink
authors.forename: W J
authors.initials: WJ
authors.lastname: van der Vijgh
authors.forename: I
authors.initials: I
authors.lastname: Klein
authors.forename: W W
authors.initials: WW
authors.lastname: ten Bokkel Huinink
authors.forename: R
authors.initials: R
authors.lastname: Dubbelman
authors.forename: J G
authors.initials: JG
authors.lastname: McVie
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016190:Carboplatin; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010529:Peritoneal Cavity / Q000378:metabolism; D010984:Platinum / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010984:Platinum; D016190:Carboplatin