Effect of Stoichiometry of Cisplatin—Alginate Complex on the Pharmacokinetics of Cisplatin

Abstract

It was previously reported that alginate forms a complex with cisplatin, increasing plasma levels of cisplatin and reducing nephrotoxicity but without decreasing in-vitro antitumour activity. We examined three kinds of cisplatin—alginate complexes with various stoichiometrics (molar ratios of uronic acid of two-, four- and tenfold to cisplatin) to clarify the effect of alginate on the pharmacokinetics of cisplatin-alginate complex. Plasma levels of cisplatin were maintained at high levels dependent upon the content of alginate. Tissue-plasma partitioning values of cisplatin (Kp) in several tissues, especially the kidney, at 48 h after administration were repressed by complexation. However, the addition of alginate at molar ratios of uronic acid residue to cisplatin of more than four-fold had no further effect on plasma level or tissue accumulation of cisplatin. Urinary excretion of cisplatin was accelerated by alginate content up to a ratio of four uronic residues to each cisplatin molecule, while a uronic acid molar ratio of ten showed no further effect. Thus, the effect of alginate on pharmacokinetics of cisplatin is dependent on the amount of alginate, and the optimal content of alginate was around a molar ratio of four, uronic acid to cisplatin.