IN-VITRO CARBOPLATIN-MESNA INTERACTION IN AQUEOUS-SOLUTION, HUMAN PLASMA AND URINE

The chemotherapeutic benefit of synergistic drug combinations and high er drug dosages has generated interest in the application of these reg imens to cancer patients. A major obstacle in the application of these strategies to the treatment of cancer is the dose-limiting toxicities of drug combinations. Sodium 2-mercaptoethane-sulfonate (mesna), a ch emoprotective drug, may reduce the nephrotoxicity of carboplatin [CBDC A, paraplatin, JM-8, cis-diammine (1,1-cyclobutane dicarboxylato) plat inum II] when administered in combination chemotherapy. The purpose of this study was to evaluate, compare and contrast in vitro the interac tion of mesna with carboplatin in aqueous solution, human plasma and u rine. Carboplatin and mesna were incubated separately and together at clinically relevant concentrations in plasma and urine. The concentrat ion of carboplatin was assayed by HPLC, and the decay of carboplatin a lone and in combination with mesna was compared. The incubation of car boplatin with mesna in human plasma up to 8 days did not result in a s tatistically significant interaction: the half-life of carboplatin in plasma when it was combined with mesna was 1.62+/-11.08 (SE) days comp ared to 1.85+/-0.04 (SE) days for carboplatin by itself. The incubatio n of drugs in fresh human urine up to 15 days gave a half-life of 3.43 +/-0.8 (SE) days for carboplatin alone and 2.78+/-0.7 (SE) days for ca rboplatin when it was combined with mesna. Our results show that carbo platin and mesna do not significantly interact in plasma. Although a s tatistically significant difference between the half-life of carboplat in and the half-life of the carboplatin/mesna combination is detected in urine, it is not likely to be clinically significant, as there is n o significant interaction detected in the first 48 h). It is thus unli kely that mesna would sub-stantially affect the pharmacokinetics of ca rboplatin when both are given together to patients as part of combinat ion chemotherapy regimens.