Comparative distribution and excretion of carboplatin and cisplatin in mice.
The comparative distribution and excretion of Carboplatin (cis-diammine-1,1-cyclobutane dicarboxylate platinum II, CBDCA, JM8) and cisplatin have been investigated in Balb C- mice following i.v. administration of the maximally tolerated doses (MTDs) of the compounds. Although the concentrations of platinum in the plasma and tissues during the alpha-phase were much higher for Carboplatin than for cisplatin, reflecting the difference in the doses used (4 vs 80 mg/kg), the tissue-to-plasma ratios were similar. During the beta-phase (1-10 days), however, both the platinum concentrations and the ratios were found to be similar for most tissues when cisplatin and Carboplatin were compared. The platinum concentrations and the tissue-to-plasma ratios of the spleen, brain, muscle, testes, ovary and bile, on the other hand, were consistently higher (two- to sixfold) after Carboplatin than after cisplatin. The highest ratios (greater than 20) were found in the kidney, liver, spleen (after Carboplatin only) and skin at 6 days after treatment. Comparison of the two compounds showed that the half-lives of platinum in the plasma and tissues during both the alpha- and beta-phases were similar, except for the spleen, in which a nine-fold greater t1/2 beta was recorded for Carboplatin than for cisplatin. The main route of excretion for the two complexes is via the kidneys, with 52% of cisplatin and 93% of Carboplatin being excreted during the first 3 days. The major part of this, however, is excreted within the 1st day. These results indicate that, although there are quantitative differences, the distribution and excretion profiles are similar for Carboplatin and cisplatin.
Siddik
Z H
ZH
Biochemical Pharmacology, Drug Development Section, Institute of Cancer Research, Surrey, England.
Jones
M
M
Boxall
F E
FE
Harrap
K R
KR
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D016190:Carboplatin; D002945:Cisplatin / Q000493:pharmacokinetics*; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics*; D011485:Protein Binding; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D001798:Blood Proteins; D009944:Organoplatinum Compounds; D016190:Carboplatin; D002945:Cisplatin