DOUBLE DUMMY COMPARISON BETWEEN ONCE AND TWICE-DAILY DOSING WITH MODIFIED-RELEASE CARBAMAZEPINE IN EPILEPTIC PATIENTS

1 Fourteen patients with refractory epilepsy on a twice daily regimen of modified-release carbamazepine (CBZ-MR, Tegretol Retard, Ciba Pharm aceuticals) completed a balanced, double-blind, double dummy, random o rder, crossover comparison of 8 weeks treatment with once (o.d.) and t wice daily (b.d.) closing. In order to obtain a profile of serum CBZ c oncentrations 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 eac 4 week treatment period. 2 Overall, trough serum drug concentrations (C(min) ) were lower with once daily dosing (C(min): 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 sign ificant differences were found in average (C(av)) or peak (C(max)) con centrations, AUC values or fluctuations in CBZ concentrations. 3 Pharm acokinetic parameters for CBZ 10, 11 epoxide, the active metabolite of CBZ, did not differ significantly between the dosage schedules. 4 Sei zure control was similar during once and twice daily dosing with CBZ-M R (median seizures/month (range), b.d. 1(0-1;4.5), 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 pati ents (n = 11) preferred treatment (P < 0.05) with once daily than twic e daily dosing (n = 3) with CBZ-MR. 7 Once daily dosing with CBZ-MR sh ould be possible in the majority of patients receiving the drug as mon otherapy.