Siddik Z H, Jones M, Boxall F E, Harrap K R
Biochemical Pharmacology, Drug Development Section, Institute of Cancer Research, Surrey, England.
Cancer Chemother Pharmacol. 1988;21(1):19-24. doi: 10.1007/BF00262732.
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.
在给Balb C小鼠静脉注射卡铂（顺二氨-1,1-环丁烷二羧酸铂II，CBDCA，JM8）和顺铂的最大耐受剂量（MTDs）后，对它们的比较分布和排泄情况进行了研究。尽管在α期卡铂在血浆和组织中的铂浓度比顺铂高得多，这反映了所用剂量的差异（4毫克/千克对80毫克/千克），但组织与血浆的比率相似。然而，在β期（1 - 10天），当比较顺铂和卡铂时，发现大多数组织的铂浓度和比率相似。另一方面，卡铂给药后，脾脏、大脑、肌肉、睾丸、卵巢和胆汁中的铂浓度和组织与血浆的比率始终较高（高出两到六倍）。在治疗后6天，肾脏、肝脏、脾脏（仅卡铂给药后）和皮肤中的比率最高（大于20）。两种化合物的比较表明，除脾脏外，α期和β期血浆和组织中铂的半衰期相似，在脾脏中，卡铂的β半衰期比顺铂长九倍。两种复合物的主要排泄途径是通过肾脏，顺铂在头3天内排泄52%，卡铂排泄93%。然而，其中大部分在第1天内排泄。这些结果表明，尽管存在定量差异，但卡铂和顺铂的分布和排泄情况相似。
