Investigations into the relative bioavailability of carbamazepine after single oral administration of three test batches of a carbamazepine-containing sustained release formulation in healthy subjects.

ABSTRACT

A bioavailability study with three test batches of a sustained release formulation of carbamazepine, which differed only in their in vitro dissolution profiles, was performed in 18 healthy subjects to compare the respective plasma concentration profiles and to determine the relative bioavailability of carbamazepine (CBZ). This investigation was designed to examine the extent to which these differences in dissolution properties can be determined from the results of in vivo tests. The randomized, single-dose, crossover study comprised three experimental periods, separated by washout intervals of three weeks' duration. A sensitive, validated HPLC method was used for the analysis of serum carbamazepine concentrations. Bioequivalence was only accepted if the 90% confidence interval (parametric or nonparametric) for the quotients of the mean values of the variables for each test and reference preparation was completely within the bioequivalence range. For this calculation, all three test preparations were compared with one another. The following relative bioavailability values were obtained A/B AUC = 87% (83%, 92%), MRT = 106% (103%, 109%), HVD = 109% (105%, 113%). C/B AUC = 106% (101%, 110%), MRT = 98% (96%, 99%), HVD = 87% (82%, 91%). C/A AUC = 124% (117%, 130%), MRT = 92% (89%, 94%), HVD = 79% (74%, 84%). There was a positive correlation between the in vitro dissolution rates of the different test batches and the respective degree of carbamazepine absorption as determined in vivo, while an inverse correlation existed between the in vitro dissolution rates on one side and the mean residence time (MRT) as well as the half value duration (HVD) on the other.(ABSTRACT TRUNCATED AT 250 WORDS)