Preliminary observations of intraperitoneal carboplatin pharmacokinetics during a phase I study of the Northern California Oncology Group |
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| Authors: | Michael W. DeGregorio Bert L. Lum Walter M. Holleran Bruce J. Wilbur Branimir I. Sikic |
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| Affiliation: | (1) Cancer Pharmacokinetics Laboratory, Children's Cancer Research Institute, Pacific Presbyterian Medical Center, San Francisco, CA, USA;(2) Cancer Research Institute, University of California, San Francisco, CA, USA;(3) School of Pharmacy, University of the Pacific, Stanford, CA, USA;(4) Division of Medical Oncology, Stanford University Medical Center, Stanford, CA, USA |
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| Abstract: | Summary The pharmacokinetic behavior of carboplatin administered by the i.p. route at a dose of 200 mg/m2 was studied during five courses of therapy in four patients with ovarian cancer. A regional pharmacologic advantage was noted with carboplatin administered by this route, with (1) peak peritoneal fluid concentrations 18-fold those in plasma, and (2) area under the curve (AUC) for the peritoneum showing a 18-fold and 6-fold increase over plasma AUC at 4 and 24 h, respectively. The mean residence time of total platinum in the peritoneum was 4.7 h. Approximately 10% and 40% of plasma platinum was protein bound at 4 and 24 h after treatment, respectively, whereas peritoneal fluid platinum showed minimal protein binding. Peak plasma platinum levels were comparable to those recorded in previous studies with i.v. doses of carboplatin. Peritoneal clearance of carboplatin in these four patients appeared to be less than that previously reported for cisplatin. Further studies are in progress with higher doses of i.p. carboplatin.Supported in part by the Louis R. Lurie Foundation, the Randy Lynn Baruh Research Foundation, and grants CA21744, CA19408, CA25827, and CA25862 from the National Institutes of Health, Department of Health and Human Services |
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