Comparative bioavailability of alpha-methyldopa normal and film tablet formulations after single oral administration in healthy volunteers

Abstract

In a single dose, randomized, cross-over study, with one week of wash-out period, the relative bioavailability of Dopegyt tablets containing 250 mg alpha-methyldopa (AMD) and Presinol film tablets with identical active ingredient content was examined in 24 healthy volunteers. Since technologically two completely different preparations (a film-tablet and a non-film-tablet) having significantly different in vitro dissolution were to be compared, both preparations were compared to a third one, AMD solution (Dopegyt solution) with 250 mg/50 ml concentration. Plasma concentrations of the drug were measured for 24 hours post-dose, applying HPLC with fluorometric detection. Pharmacokinetic parameters calculated from individual data (AUC0-infinity, AUC0-t, Cmax, Cmax/AUC0-infinity, t(max)) were evaluated statistically. Wilcoxon's nonparametric test and the four-way variance analysis could not detect any significant difference at the usual a=95% probability level in these pharmacokinetic parameters of the two tablet preparations. For AUC0-infinity at the 90% probability level, the confidence interval was 0.883-1.237 (with an estimated geometric mean of 1.045), for the test/reference ratio of Dopegyt and Presinol tablets, thus the two preparations proved to be bioequivalent. The relative bioavailability of Dopegyt (test preparation) and Presinol (reference preparation) calculated from the AUC0-infinity values was 116.7+/-56.7% that also confirmed bioequivalence. The results of all the applied statistical tests suggest that Dopegyt and Presinol can be considered as bioequivalent preparations.

Approaches to the Development of Bioanalytical Methods for Determination of Unstable Substances in Biological Fluids

“…Выявление подходов к разработке методик определения нестабильных соединений в плазме было выполнено на примере микофеноловой кислоты (МФК), содержащей в структуре один фенольный гидроксил и в процессе метаболизма образующей О-ацилглюкуронид (АГМФК) и фенольный глюкуронид (ФГМФК) [8,9], деметилированной мебевериновой кислоты (ДМК), также содержащей в структуре один фенольный гидроксил и метаболизирующейся с образованием фенольного глюкуронида (ФГДМК) [22], и метилдопы (МД), содержащей два фенольных гидроксила (рис. 1) [30,32,35,36]. Данные методики разрабатывались для изучения биоэквивалентности (БЭ) лекарственных препаратов данных веществ.…”

Single dose bioequivalence study of α-methyldopa tablet formulations using a modified HPLC method

“…The method used wasvalidated forspecificity, accuracy,precision and sensitivity.The pharmacokineticparameters (C max , AUC 0-t ,AUC 0-1 )werestatisticallycompared byanalysisof variance(ANOVA)for test and referencef ormulations. [4].Although in previous studies,spectrofluorimetric, gasand liquid chromatographicmethodshavebeen reported tobeused fordetermination of a -methyldopa in biologicalf luids [4][5][6], in the presents tudyin which the bioavailability of twotabletformulationsof amethyldopahasbeen compared,the plasmaconcentrationsof methyldopawered etermined using amodified HPLC method withf luorescenced etection. The new HPLC method wasv alidated fors pecificity,a ccuracy, precision and sensitivity.Furthermore,the pharmacokineticparameters of test and referencef ormulations (C max ,A UC 0-t ,A UC 0-1 )werestatisticallycompared by analysisof variance(ANOVA).…”