ABSTRACT
In preparation for a prospective controlled study of mexiletine in the treatment of epilepsy, a preliminary study of serum concentrations after multiple doses was performed with 8 institutionalized Caucasian adult males with uncontrolled seizures and similar weight, medical regimen, and seizure classification. Two patients each received daily dosages of 200, 400, 600 or 800 mg mexiletine administered in capsules four times a day for 7 days, in addition to their usual medication. Serum concentrations of mexiletine were determined by the Kupferberg-Yonekawa method. After the first day, serum concentrations of mexiletine were significantly higher for the 600 and 800-mg dosages than for the 200- and 400-mg dosages. The differences in serum concentration between the 200- and 400-mg dosages and between the 600- and 800-mg dosages were not significant. Serum concentrations for the 200-mg and 400-mg dosages were generally below 400 ng/ml, whereas at dosages of 600- and 800-mg, serum concentrations ranged from 400 to over 1,100 ng/ml, after the first day. Optimal dosage for this population appeared to be at least 800 mg/day. Half-life ranged from 3.5 to 7.8 hr.
Subject(s)
Anticonvulsants/administration & dosage , Epilepsy/drug therapy , Mexiletine/administration & dosage , Propylamines/administration & dosage , Adult , Dose-Response Relationship, Drug , Humans , Male , Mexiletine/blood , Mexiletine/therapeutic useABSTRACT
The efficacy and bioavailability, and tolerance to carbamazepinee when administered with phenobarbital or phenytoin or with both drugs were evaluated in a prospective, double-blind study of patients whose seizures were not completely controlled by currently available antiepileptic drugs in usually therapeutic dosages as determined by serum levels. During each of four 21-day treatment periods, one fourth of the patients received daily doses of: (1) carbamazepine (1,200 mg) and phenytoin (300 mg); (2) carbamazepine (1,200 mg) and phenobarbital (300 mg); (3) phenytoin (300 mg) and phenobarbital (300 mg); or (4) carbamazepine (1,200 mg), with phenytoin (300 mg) and phenobarbital (300 mg). The treatment periods were separated by 2 wk of each patient's usual prestudy medication. Treatment with all three drugs was the most efficacious for seizure control. Serum carbamazepine concentration was significantly decreased when the drug was administered with either phenytoin or phenobarbital or both.
