The Prevalence of Valproic-Acid-Associated Hyperammonaemia in Patients with Intractable Epilepsy Resident at the Chalfont Centre for Epilepsy

Abstract Valproic acid (VPA)-induced hyperammonaemia, with or without clinical or laboratory evidence of hepatoxicity, is well-documented. This study was designed to assess the prevalance of hyperammonaemia in institutionalised patients treated with VPA chronically and to identify contributing factors. Eight-two refractory patients (60 men and 22 women; mean age, 39 years; mean weight, 70.1 kg), were studied. Ten patients were on VPA monotherapy, and 72 were on antiepileptic drug (AED) polytherapy. Fourteen epileptic patients on AED polytherapy excluding VPA (patient controls) and 10 volunteers (healthy controls) were also evaluated. VPA dose ranged between 7.1 and 71.4 mg/kg/day and was associated with VPA plasma concentrations of 114–753 and 77–1,315 μmol/L pre-and postprandially, respectively. A plasma ammonium (NH 4 + ) concentration of 50 μmol/L is considered the upper normal limit in healthy adult subjects. Pre- and postprandial plasma NH 4 + concentrations >50 μmol/L were seen in 20% and 30% of VPA-treated patients, respectively. In contrast, all healthy and patient controls had plasma NH 4 + concentrations 4 + concentration. The highest VPA dose (71.4 mg/kg/day) was associated with the highest (95 μmol/L) plasma NH 4 + concentration. There was a significant correlation ( r = 0.61; p 4 + and VPA concentration postprandially in male patients taking VPA and carbamazepine in combination. It is concluded that, although VPA medication can be associated with elevated plasma NH 4 + concentrations that are not clinically significant in many patients, caution is necessary when prescribing VPA.