Drug metabolism and disposition : the biological fate of chemicals
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Drug Metab. Dispos. · Mar 1994
Pharmacokinetics of tetraplatin administered intraperitoneally with reduced glutathione in mice.
Tetraplatin (Ormaplatin) has been developed as a second generation platinum complex because of its good antitumor activity against some cisplatin-resistant tumor cell lines. It is currently in clinical trials. Its reduction to diaminocyclohexane (DACH)-dichloroplatinum(II) [DACH-Pt(II)Cl2] or closely similar species is essential for binding to DNA to produce the desired antitumor effects. ⋯ Plasma and ascitic fluid from tumor-bearing mice demonstrated equivalent abilities to reduce tetraplatin rapidly. However, tetraplatin treatment of intraperitoneal-inoculated L1210/0 (parent) or L1210/DDP (cisplatin-resistant) tumor cells was unaffected by GSH. As GSH lowered systemic tetraplatin exposure in vivo without compromising antitumor activity against peritoneal tumor models, the combination of thiol and tetraplatin may be clinically useful in the treatment of intraperitoneal disseminated cancers.