Abstract
The uptake of cisplatin and its metabolites into rat and rabbit renal cortical slices was investigated. Under anaerobic conditions the cisplatin uptake rate was significantly reduced by pretreatment with dinitrophenol and by organic cationic compounds (cimetidine, verapamil and quinidine). Verapamil competitively inhibited the uptake of cisplatin (apparent inhibitory constant (Ki) = 204.5 ± 43.0 μM). There was very little uptake of the cisplatin metabolite formed by complexation with glutathione. In addition, both aquated cisplatin and a metabolite formed by complexation with thiosulphate were taken up to a very low extent at 37°C compared with unchanged cisplatin. These results suggest that the intact chemical structure of cisplatin may be required for transport of cisplatin into the kidney and cisplatin may be partly transported via organic cation transport systems.
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