A comparative bioavailability study of a generic capsule formulation containing carbocysteine.
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).
Jovanović
D
D
National Poison Control Centre, Military Medical Academy, Belgrade, Serbia & Montenegro. NCKTVMA@Eunet.yu
Cusić
S
S
Segrt
Z
Z
Dordević
D
D
Vehabović
M
M
Potogija
N
N
D000996:Antitussive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D002233:Carbocysteine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004339:Drug Compounding; D016568:Drugs, Generic; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D013810:Therapeutic Equivalency
D000996:Antitussive Agents; D002214:Capsules; D016568:Drugs, Generic; D002233:Carbocysteine