Simultaneous first- and zero-order absorption of carbamazepine tablets in humans.

The absorption kinetics of carbamazepine (5H-dibenz[b,f]azepine-5-carboxamide) in healthy adult volunteers was investigated following a single 400-mg (2 X 200-mg) oral dose of commercially available conventional tablets (Tegretol). Wagner-Nelson plots of the data from all subjects (n = 10) showed that the fraction remaining to be absorbed declined in a biphasic manner, suggesting a mixed order of absorption. A model assuming the absorption of carbamazepine by simultaneous first-order and zero-order rates was used to describe the overall absorption process. Model parameters (and their mean +/- SD values) were: alpha, the fraction of the dose absorbed at a first-order rate (0.646 +/- 0.070); Ka, the first-order absorption rate constant (0.45 +/- 0.13 h-1); and tdur, the duration of the zero-order absorption component (36.0 +/- 4.4 h). If complete absorption can be assumed, then the corresponding average zero-order rate was 4.0 mg X h-1. The results indicate that 35% of the available dose is absorbed at a zero-order rate. These data suggest a prolonged constant rate of absorption due to continued delivery during its transit in the intestine. In addition, an assessment of the mean absorption time, based on the parameters from the model described above, compared closely (7.95 versus 8.44 h) with the mean absorption time estimated from an analysis of the fraction remaining to be absorbed versus time plot using a noncompartmental approach.