Pharmacokinetics cisplatin compounds

Interpretation of pharmacokinetic data is also complicated by biotransformation processes. Cisplatin is metabolized to various aquated species and in the low-chloride intracellular environment these predominate. Plati-num(IV) compounds are converted rapidly to platinum(II) derivatives in plasma, and multiple distinct circulating molecular species may be produced [223], While some HPLC assays may distinguish among metabolites, sensitivity often limits resolution of the various molecular species. Pharmacokinetic data should be interpreted accordingly. Recently it has been possible... 

At the preclinical level, oral antitumor activity has been observed with two other classes of platinum compound, the PtIV monocarboxylate, C(5)-OHP-C1, and the first Ptn complex to exhibit oral activity, the sterically hindered AMD473. Now licenced to Zeneca, AMD473 exhibited promising circumvention of acquired cisplatin resistance against both in vitro and in vivo preclinical models. Together with the drug s favourable pharmacokinetic and toxicology profile in rodents (myelosuppression was dose-limit-... 

Vermeulen NP, Baldew GS, Los G, et al. 1993. Reduction of cisplatin nephrotoxicity by sodium selenite. Lack of interaction at the pharmacokinetic level of both compounds. Drug Metab Dispos Biol Fate Chem 21(l) 30-36. 

The in vitro interactions of the cysteine-rich intracellular protein Zn7-metal-lothionein with cisplatin and transplatin and the histidine-rich proteins Hpni32,i33 HspA with a bismuth antiulcer compound were investigated, respectively. These kinds of interactions may play a crucial role in the metabolism of various metallodrugs. Notably, drug binding to plasma proteins has a strong influence on their biodistribution, biotransformation, and pharmacokinetics, and therefore merits further characterizations. 

---