Relative bioavailability of almitrine bismesylate in humans

Abstract

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,l 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 3.26 h, 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 less than 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.

One year administration of almitrine bismesylate (vectarion) to chronic obstructive pulmonary disease patients: Pharmacokinetic analysis

“…In addition, elimination half-lives have been reported for both intravenous and oral single dose administration of almitrine bismesylate ranging from 40 to 50 h. 4,5 Single dose studies involving oral administration of almitrine bismesylate solid and liquid formulations for the purpose of establishing bioequivalency and determining bioavailability report elimination half-lives ranging from 60 to 100 hours. 6 Studies have been conducted administering almitrine bismesylate up to 56days which have suggested that no apparent steady state levels are attained.' Therefore, in order to properly design an appropriate multiple dosing regimen, studies were implemented in the United States in stable COPD patients for 1 year.…”