1. Eight healthy subjects took part in a balanced, double‐blind, crossover comparison of conventional carbamazepine (Tegretol, Ciba‐ Geigy Ltd, CBZ‐C) and a novel controlled‐release formulation (Tegretol CR Divitabs, Ciba‐Geigy Ltd; CBZ‐CR). An initial single dose of either preparation was followed 1 week later by a 2 week course of 200 mg twice daily. 2. Following the single dose, CBZ‐CR produced a concentration plateau from 6‐56 h at 50‐60% of the CBZ‐CR peak. 3. After 2 weeks' treatment, CBZ daytime levels measured as area under the concentration‐time curve over a dosage interval were 7% lower with CBZ‐ CR, but this difference was not statistically significant. 4. CBZ‐CR showed less diurnal fluctuation (12%) of CBZ than CBZ‐C (24%; P less than 0.025) with less rapid changes in concentration (P less than 0.02). 5. Diurnal fluctuation of free CBZ and of CBZ 10,11 epoxide, the active metabolite, did not differ significantly between the two preparations. 6. Auto‐induction of CBZ metabolism resulted from the administration of both formulations. The mean elimination half‐life was 23 h (CBZ‐C) and 25 h (CBZ‐CR) after dose 29 compared with a base‐line value of 37 h (both P less than 0.02). Antipyrine metabolism was also induced to a similar extent in both legs of the study (P less than 0.01). 7. No significant alteration in psychomotor function was demonstrated with either preparation. 8. CBZ‐CR fulfils the criteria for a controlled‐release preparation with comparable apparent bioavailability to CBZ‐C. Further pharmacokinetic and, more importantly, pharmacodynamic studies are required in epileptic patients to confirm a clinical advantage over the currently available formulation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.