Bioequivalence evaluation of two tablet formulations of carbocysteine in healthy Chinese men

A randomized, two-way crossover study was conducted in 20 healthy Chinese male volunteers to compare the bioequivalence of two tablet formulations of carbocysteine as required by China State Food and Drug Administration. Test and reference tablets were administered as a single dose on two treatment days separated by a 1-week washout period. After dosing, serial blood samples were collected for a period of 10 hours. Carbocysteine in human plasma was determined by a sensitive, selective, reproducible and accurate liquid chromatography-tandem mass spectrometry (LC/MS/MS) method validated following international guidelines. Pharmacokinetic parameters including Cmax, Tmax, t1/2b, AUC0-t, and AUC to infinity were determined from plasma concentration of both formulations, and it is interesting to find that there is maybe ethnic variation in the Cmax value of carbocysteine. Statistical modules (analysis of variance [ANOVA] and 90% confidence interval [CI]) were applied to Cmax, AUC0-t, and AUC 0-infinity to assess the bioequivalence of the two tablets. No significant differences between the tablets were found, and the 90% CI fell within the China and US FDA accepted range of 80% to 125%.The results indicate that the two tablet formulations of carbocysteine are equivalent in the rate and extent of absorption.