Relative bioavailability of almitrine bismesylate in humans

Bioavailability and bioequivalency studies of almitrine bismesylate from U.S. manufactured film coated, waxed, 50 mg tablets were compared in 34 normal healthy volunteers to 50 mg European film coated, waxed and unwaxed, tablets and a 0·5 per cent (w/v) oral reference solution of almitrine bismesylate in d,1 malic acid. The U.S. manufactured formulations were 85·88 and 87·85 per cent of the calculated mean area under the individual concentration‐time curve for almitrine bismesylate reference solution compared to 88·40 and 88·86 per cent for the waxed and unwaxed film coated European tablets, respectively. The mean peak plasma concentrations for the U.S. formulations were 176·3 ng ml −1 and 180·1 ng ml −1 compared to 196·3 and 200·1 ng ml −1 for the waxed and unwaxed European formulations, respectively. Mean time to peak plasma concentrations for the two U.S. formulations and the waxed and unwaxed European formulations were 3·22, 3·33, 3·06, and 3·26h, respectively. In addition, the oral reference solution yielded a mean peak plasma concentration of 222·8 ng ml −1 and a mean time to peak plasma concentration of 2·68 h. Analysis of variance and multiple range comparisons ( p < 0·05) indicated that the tablet formulations were bioequivalent. The results of this study show that the U.S. formulated almitrine bismesylate tablets exceed 85 per cent relative bioavailability with respect to the oral reference solution and are bioequivalent compared to the marketed standard European tablet formulations.