Penetration of carboplatin and cisplatin into rat peritoneal tumor nodules after intraperitoneal chemotherapy.
Platinum distribution was studied in rat peritoneal tumors after i.p. treatment with equimolar doses of carboplatin and cisplatin. Low platinum concentrations (4 ppm) were detected in the periphery of the tumor after carboplatin treatment, whereas no platinum was detected 0.5 mm in from the periphery. In contrast, after cisplatin treatment, high platinum concentrations (29 ppm) were measured in the periphery of the tumor and moderate concentrations (14 ppm) were measured in the center. Only following increased carboplatin doses were low platinum concentrations detectable in the tumor. The total platinum concentration in the tumors was determined after equimolar administration of both drugs. In all, 7 times more platinum was detected after cisplatin treatment than after carboplatin treatment, and 10 times more carboplatin than cisplatin had to be injected to obtain comparable platinum concentrations in the tumors. When single cells were incubated with equimolar concentrations of carboplatin and cisplatin, 6-7 times more platinum was found in cells treated with cisplatin. However, pharmacokinetic studies favored i.p. administration of carboplatin because the clearance of this compound from the peritoneal cavity, expressed as t1/2 beta, was lower than that of cisplatin (239 vs 78 min), resulting in an AUC in the peritoneal cavity for both total and ultrafiltered drug that was almost 3 times higher for carboplatin than cisplatin. The AUC for ultrafiltered carboplatin in plasma was 2-fold that for cisplatin (2,801 +/- 210 vs 1,334 +/- 431 microM m). The present study demonstrated that in spite of the pharmacological advantages of carboplatin, its capacity to penetrate into peritoneal tumors and tumor cells is far lower than that of cisplatin.
Los
G
G
Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam.
Verdegaal
E M
EM
Mutsaers
P H
PH
McVie
J G
JG
D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D016190:Carboplatin / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D002945:Cisplatin / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013052:Spectrometry, X-Ray Emission / Q000379:methods; D013054:Spectrophotometry, Atomic / Q000379:methods; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D016190:Carboplatin; D002945:Cisplatin