Plasma Concentrations

Blood level data were available from 12 of the 17 patients treated on both dose schedules. Their mean daily dose of mexiletine was 725 mg every 8 h and 657 mg every 12 h, while individual doses averaged 242 mg every 8 h and 328 mg every 12 h. The mean trough blood levels in these patients were 0.80 ±0.55 jig/ml every 8 h and 0.73 ± 0.57 every 12 h, while the peak levels of mexiletine averaged 1.2 ±0.60 |JLg/ml every 8 h and 1.6±0.64 |xg/ml every 12 h.

Mean trough levels in patients receiving the same daily dose on both dosing regimens (200 mg three times a day or 300 mg twice a day) were 1.2 ± 0.5 and 1.4 ±0.7 jig/ml, respectively. The difference between these values is not statistically significant.

Side Effects

All the 31 patients originally admitted were included in the safety evaluation.

Of the 17 patients treated on both regimens, 11 experienced side effects; these were tolerable and required no interruption of treatment. In the great majority of cases the symptom or symptoms were first noted within a day after administration of a given dose had begun. The most common symptoms were upper gastrointestinal distress (eight patients) and lighthead­edness (five patients). Other reactions, occurring in one patient each, were tremor, change in appetite and headache, tinnitus, clouded sensorium and diaphore­sis. No adverse cardiovascular effects were recorded.

Seven of the 11 patients with side effects experi­enced them on both regimens at all dose levels, while among the other four patients, one experienced them only on the 8-h schedule and two others only on the 12-h schedule; the fourth patient suffered upper gastrointestinal distress, tremor and lightheadedness only after the initial loading dose.

Two patients whose PVC reductions on 200 mg every 8 h were greater than 50 percent (86.5 and 55.8 percent, respectively) failed to go on to the 12-h dosage regimen because of side effects. These com­prised dizziness, nausea, vomiting, sweating and blurred vision in one of the patients, a woman of age 68, and nausea, constipation and oliguria in the other, a 74-year-old man. Neither of these two patients was in the group that had been successfully treated with mexiletine before the study.

No clinically significant abnormalities in hemato­logic studies, blood chemistry values, liver function tests or urinalysis values were observed during mexi­letine treatment.