Oral bioavailability of mesna tablets

Abstract

To test the feasibility of uroprotection with sodium 2-mercaptoethane-sulfonate (mesna) in tablet form the bioavailability of mesna tablets was determined in healthy volunteers by HPLC. The area under the plasma concentration-time curve (AUC) of free mesna was significantly lower following oral (110 μmol.l⁻¹.h⁻¹; 95% CI 98–122) than following i.v. administration of 1.2 g of mesna (201 μmol.l⁻¹.h⁻¹; 95% CI 158–244). The AUC for total mesna, i.e. dimesna and mixed disulfides, however, were comparable in the two groups, with 628 (539–717) and 772 (713–831) μmol.l⁻¹.h⁻¹, respectively. The mean residence time was significantly longer following oral mesna, at 79 (76–83) min vs 239 (229–250) min. Following oral mesna 51.1% (46.2–56.0%) of the administered dose was recovered in the urine in 24 h, compared with 60.6 (53.6–67.6)% in 4 h following i.v. mesna, and the average concentration of mesna in the urine exceeded 3 mmol.l⁻¹ for 8 h. The data indicate that mesna in tablet form has an adequate bioavailability for uroprotection and therefore may be preferable to liquid mesna, which has an unpleasant taste. Oral mesna has a longer mean residence time than i.v. mesna, which means that uroprotection can be achieved with longer dosing intervals.