Double dummy comparison between once and twice daily dosing with modified-release carbamazepine in epileptic patients

Abstract

1. Fourteen patients with refractory epilepsy on a twice daily regimen of modified-release carbamazepine (CBZ-MR. Tegretol Retard. Ciba Pharmaceuticals) completed a balanced, double-blind, double dummy, random order, crossover comparison of 8 weeks treatment with once (o.d.) and twice daily (b.d.) dosing. In order to obtain a profile of serum CBZ concentrations over 24 h on once daily dosing, patients were randomised to taking it in the morning (o.d. a.m.) or evening (o.d. p.m.) for 4 weeks. Each treatment was taken with a placebo of the other and total tablet numbers were matched. Blood sampling was undertaken 0, 2, 4, 6, 8, 10, 12 and 24 h after the morning tablets at the end of each 4 week treatment period. 2. Overall, trough serum drug concentrations (Cmin) were lower with once daily dosing (Cmin: b.d. 7.5 mg l-1, o.d. 6.5 mg l-1, P < 0.05, 95% CI of the difference -1.3 to -0.1), but no significant differences were found in average (Cav) or peak (Cmax) concentrations, AUC values or fluctuations in CBZ concentrations. 3. Pharmacokinetic parameters for CBZ 10.11 epoxide, the active metabolite of CBZ did not differ significantly between the dosage schedules. 4. Seizure control was similar during once and twice daily dosing with CBZ-MR (median seizures/month (range): b.d. 1 (0-14.5), o.d. 0.5 (0-11), NS, 95% CI of the difference -1.8 to + 0.25). 5. There were no differences in psychomotor performance between the treatment periods. 6. More patients (n = 11) preferred treatment (P < 0.05) with once daily than twice daily dosing (n = 3) with CBZ-MR. 7. Once daily dosing with CBZ-MR should be possible in the majority of patients receiving the drug as monotherapy.