Plasma Pharmacokinetics, Urinary Excretion, and Tissue Distribution of Platinum Following IV Administration of Cyclobutanedicarboxylatoplatinum-II and cis-Platinum to Rabbits

Abstract

Cisdiamminedichloroplatinum (Cisplatin) is an effective agent in the treatment of several human cancers (3). Its clinical effectiveness is limited, however, by dose limiting toxicities such as renal failure, nausea and vomiting, and hearing loss (8,10). Ever since the clinical introduction of cisplatin in the early 1970’s efforts have been underway to discover or develop additional platinum complexes that would have a greater therapeutic index, i.e. either greater antitumor activity with the same degree of toxicity, or less toxicity so that greater doses could be administered. It has been only recently that large scale clinical trials of several of the most promising analogs have been undertaken. Cyclobutanedicarboxylatoplatinum (II) (CBDCA; JM-8; NSC 241240) is one of the second generation analogs of cisplatin that is currently undergoing large scale clinical trials (1). In these early clinical studies, evaluation of the pharmacokinetics and renal excretion of this analog have been conducted but similar data have not yet appeared for animals. We have evaluted plasma decay, urinary and biliary excretion, and organ distribution of CBDCA at various times after a single IV administration of 2 different doses to rabbits and compared the behavior of CBDCA to cisplatin.