Chronic valproic acid therapy and incidence of increases in venous plasma ammonia

Results are described on the association of elevated ammonia (NH3) with valproic acid (VPA) therapy in a large group (n = 157) of randomly selected, chronically medicated (greater than 2 years) outpatients. The highest incidence (45.5%) of elevations occurred in patients comedicated with VPA-phenobarbital (PB)-phenytoin (PHT) combinations, followed by VPA-PB (33.3%) and VPA-PHT (15.4%). No NH3 elevations were detected in all patients (n = 38) on chronic VPA monotherapy. Considering the total sample (n = 157), NH3 concentrations were found to be linearly and directly correlated with VPA plasma concentration (n = 125, r = 0.249, p less than 0.001), PB concentration (n = 86, r = 0.411, p less than 0.001), sum of VPA-PB concentration (n = 60, r = 0.721, p less than 0.001), and sum of VPA-PB-PHT concentration (n = 33, r = 0.802, p less than 0.001). When patients in the subgroups (n = 73) that included all the patients with elevated NH3 were separated into one group (n = 47) with normal NH3 (less than or equal to 0.70 micrograms/ml) and one group (n = 26) with elevated NH3 (greater than or equal to 0.71 micrograms/ml), Student's t tests for equality of means showed that the group with elevated NH3 had a significantly higher mean plasma concentration for VPA, PB, sum of VPA-PB, and sum of VPA-PB-PHT (all at p less than 0.001) when compared with the normal group.(ABSTRACT TRUNCATED AT 250 WORDS)