Pharmacokinetics and bioequivalence of two trimebutine formulations in healthy volunteers using desmethyl-trimebutine levels

Trimebutine tablets (dimethylamino-2-phenyl-2-n-butyl-3,4,5-trimethoxybenzo ate maleate, CAS 34140-59-5, reference) and a new tablet formulation (Eurog alena, test) were administered in 24 healthy volunteers of both sexes accor ding to a cross-over design, in a single dose of one 100 mg tablet of each formulation. Blood samples were drawn off over a 24-h period, before (time 0) and after each administration at specific intervals. Trimebutine and its main active metabolite, desmethyl-trimebutine, were measured in plasma usi ng a validated HPLC method with UV detection. For both compounds, the sensi tivity was 20 ng.ml(-1) and the analytical method was proved to be linear f or concentrations between 20 ng.ml(-1) and 5000 ng.ml(-1), with a variabili ty less than 11 %. The non-compartmental method was used for pharmacokinetic analysis. The con fidence interval approach was used for comparison of the formulations accor ding to the EU guidance note on bioavailability and bioequivalence on C-max , AUC(0-t) and AUC(0-infinity), log transformed. T-max values were statisti cally compared using the Friedman non-parametric test. No trimebutine concentration was measured in the plasma samples. The obtain ed data with desmethyl-trimebutine proved the bioequivalence of the two tes ted formulations.