PURPOSE: To determine if three marketed generic carbamazepine tablets were bioequivalent to the innovator formulation, as well as to each other. In addition, to examine in vivo-in vitro relationships among the four formulations. METHODS: Each formulation was given as a single dose to 18 healthy male and female subjects using a crossover design. Blood samples were collected for 169 hr. Carbamazepine was assayed by HPLC with UV detection. RESULTS: In vivo fraction absorbed plots indicated that the three generic formulations were absorbed more rapidly than the innovator product, and the mean time of maximum plasma concentration was 6-7 hr sooner for the generic formulations. The mean maximum plasma concentration ranged from 17-19 percent higher for the generic products compared to the innovator, and the 90% confidence limits for Cmax data ranged from 11 1% to 126%. The mean AUC(0-infinity) for the generic products ranged from 101-104% compared to the innovator, and the confidence limits for AUC ranged from 97-108%. CONCLUSIONS: The generic products were all more rapidly absorbed than the innovator, but simulations of steady-state concentrations indicated that it would be unlikely that these differences would have any significant clinical effect. An excellent association was seen between the Cmax and the percent of drug dissolved in vitro. The correlation was used to accurately predict the Cmax of four other 200 mg tablets evaluated in an earlier study.
PURPOSE: To determine if three marketed generic carbamazepine tablets were bioequivalent to the innovator formulation, as well as to each other. In addition, to examine in vivo-in vitro relationships among the four formulations. METHODS: Each formulation was given as a single dose to 18 healthy male and female subjects using a crossover design. Blood samples were collected for 169 hr. Carbamazepine was assayed by HPLC with UV detection. RESULTS: In vivo fraction absorbed plots indicated that the three generic formulations were absorbed more rapidly than the innovator product, and the mean time of maximum plasma concentration was 6-7 hr sooner for the generic formulations. The mean maximum plasma concentration ranged from 17-19 percent higher for the generic products compared to the innovator, and the 90% confidence limits for Cmax data ranged from 11 1% to 126%. The mean AUC(0-infinity) for the generic products ranged from 101-104% compared to the innovator, and the confidence limits for AUC ranged from 97-108%. CONCLUSIONS: The generic products were all more rapidly absorbed than the innovator, but simulations of steady-state concentrations indicated that it would be unlikely that these differences would have any significant clinical effect. An excellent association was seen between the Cmax and the percent of drug dissolved in vitro. The correlation was used to accurately predict the Cmax of four other 200 mg tablets evaluated in an earlier study.
Authors: Bernhard J Steinhoff; Uwe Runge; Otto W Witte; Hermann Stefan; Andreas Hufnagel; Thomas Mayer; Günter Krämer Journal: Ther Clin Risk Manag Date: 2009-06-22 Impact factor: 2.423