Platinum compounds pharmacokinetics

Optimization of the pharmacokinetic profile of trans-platinum compounds may eventually produce a clinically effective agent. 

Table VII. Disposition and Pharmacokinetics of Mercury and Platinum Compounds in the Dogfish Shark6...

Platinum-based compounds are commonly used as cancer treatment agents. Pharmacokinetic studies of these antitumor drugs require ultratrace analysis. Electrothermal vaporization ICP-MS provides low detection limits for small samples [256]. High-performance liquid chromatography with ICP-MS detection allows speciation of platinum compounds in tissues [256]. LA-ICP-MS can be used to study the distribution of platinum in tissues and tumors [256]. Natural levels of Pt are below typical quadrupole ICP-MS detection limits [257]. 

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-... 

Lipp HP, Bokemeyer C. Clinical pharmacokinetics of cytostatic drugs efficacy and toxicity (2.2. platinum compounds as anticancer drugs). In Lipp HP, editor. Anticancer drug toxicity prevention, management and clinical pharmacokinetics. New York-Basel Marcel Dekker Inc, 1999 61-81. 

Microwave acid digestion of the tissue, blood, serum, etc., can be used to prepare samples for metal analysis. The ICP-OES method is useful for monitoring the distribution of platinum compounds in the body but the information alone is not sufficient to support rigorous pharmacokinetic studies required to fully understand the total functionality as a cancer killing drug. 

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... 

Within the context of toxicological and clinical importance, speciation studies have been focused on relatively few elements, mainly aluminum, antimony, arsenic, chromium, iodine, lead, mercury, platinum, selenium and tin. However, coupled HPLC-ICP-MS has most often been used for speciation of arsenic, selenium, iodine and, to a lesser extent, mercury. The primary species of these elements include different oxidation states, alkylated metal and/or metalloid compounds, selenoamino acids and selenopeptides.In addition, applications in smdies on the pharmacokinetics of metal-based drugs (mainly platinum complexes) and metalloproteins should be included. " In the following sections, the advances in speciation smdies of individual elements are reviewed. 

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