ABSTRACT
The bioequivalence of two carbocysteine capsulae preparations was assessed in 18 healthy volunteers who received a single 750 mg dose of each carbocysteine formulation, and a new sensitive method for the quantification of carbocysteine in human plasma was developed. The study was conducted using an open, randomized, two-sequence, two-period crossover design with a week washout period between the succesive treatments. Plasma samples were obtained over a 12-hour period and analyzed by high performance liquid chromatography coupled to electrospray ionization-mass spectrometry. Either a multiplicative statistic model for concentration-dependent parameters or an additive approach for time-related parameters were used for the comparison of pharmacokinetic parameters describing both the early and total exposure to carbocysteine. The respective 90% confidence limits [CL] of the individual ratios of geometric means were 0.898 to 1.112 [point estimate 0.999] for Cmax and 0.923 to 1.210 [point estimate 1.057] for AUC(0-infinity), while the difference between times elapsed to reach Cmax was insignificant [p = 0.4497]. Since both 90% CL for the log-transformed AUC(0-infinity) and Cmax geometric mean ratios were included in the proposed 0.80-1.25 interval, test drug (Bronchobos capsules) was considered bioequivalent to the reference one (Mucopront capsules).
