ACUTE ORAL LOADING OF CARBAMAZEPINE-CR AND PHENYTOIN IN A DOUBLE-BLIND RANDOMIZED STUDY OF PATIENTS AT RISK OF SEIZURES

The serum levels and side effects of,an acute oral loading dose-schedu le of carbamazepine (CBZ) divitabs [CBZ controlled release (CR)] and p henytoin (PHT) were assessed in patients at risk of seizures. CBZ-CR a nd PHT were administered to 42 adult patients (21 each) at a dosage of 20 mg/kg with a minimum and maximum dosage of 1,200 and 1,600 mg in p atients weighing <60 and >80 kg, respectively. CBZ-CR was given as sin gle loading dose; PHT was split, with two thirds of the dose administe red at 0 h and one third administered 2 h later. The 24-and 36-h doses were assessed according to the nystagmus status at 24 h. Mean CBZ ser um levels (percentage of subjects with level >4 mu g/ml shown in paren theses) were 0.0 (0%), 5.2 (62%), 6.7 (81%), 6.8 (95%), and 6.1 mu g/m l (95%) at 0, 4, 8, 24, and 48 h after loading, respectively, and mean PHT levels (percentage of subjects with PHT level >10 mu g/ml in pare ntheses) were 0.1 (0%), 13.2 (86%), 16.3 (100%), 16.3 (100%), and 15.4 mu g/ml (82%). One subject in the CBZ group and 3 in the PHT group vo mited. Clinical effects did not differ significantly between treatment groups and are reported. Acute doses of CBZ-CR 20 mg/kg and PHT 20 mg /kg (two-thirds at 0 h and one-third at 2 h) provided therapeutic leve ls in most patients in less than or equal to 4 h and were well tolerat ed.