Acute oral loading of carbamazepine-CR and phenytoin in a double-blind randomized study of patients at risk of seizures.

Summary: The serum levels and side effects of, an acute oral loading dose-schedule of carbamazepine (C) divitabs [CBZ controlled release (CR)] and phenytoin (PHT) were assessed in patients at risk of seizures. CBZ-CR and 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 patients weighing 80 kg, respectively. CBZ-CR was given as single loading dose; PHT was split, with two thirds of the dose administered 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 serum levels (percentage of subjects with level >4 μg/ml shown in parentheses) were 0.0 (0%), 5.2 (62%), 6.7 (81%), 6.8 (95%), and 6.1 μg/ml(95%) at 0, 4, 8, 24, and 48 h after loading, respectively, and mean PHT levels (percentage of subjects with PHT level >10 μg/ml in parentheses) were 0.1 (0%), 13.2 (86%), 16.3 (loo%), 16.3 (l00%), and 15.4 pg/ml (82%). One subject in the CBZ group and 3 in the PHT group vomited. 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 levels in most patients in G4 h and were well tolerated.