Serial free and plasma valproic acid and phenytoin monitoring and drug interactions.

In 12 institutionalized epilepsy patients who had been treated 19 months (SD +/- 5) with valproic acid, 27.0 mg/kg (SD +/- 11.9), phenytoin, 6.33 mg/kg (SD +/- 1.36), and co-anticonvulsants, the mean percentage of daily free valproic acid was 11.72 (SD +/- 2.10) and of phenytoin 20.39 (SD +/- 3.32). By serial within-day blood samplings for a.m., noon, and p.m. periods, the diurnal variation of percentage free valproic acid and phenytoin was determined for each patient. For morning and noon periods the variations in the percentages of free valproic acid and phenytoin were independent of each other, correlation coefficients (r) being zero for each period. In contrast, for early p.m. the correlation coefficient was highly significant at r = 0.894 (p less than 0.01). It is apparent that diurnal variations in the percentages of free valproic acid and phenytoin occur even in patients who have been treated with these compounds for more than a year.