Plasma concentrations of vigabatrin in epileptic patients

Objective: To measure plasma concentrations of vigabatrin in a group of 30 adult epileptic patients with complex partial seizures (CPS) refractory to conventional antiepileptic drugs. With a view to better defining the drug's dose-response relationships in the presence of concomitant alternative antiepileptic drugs. Methods: High-performance liquid chromatographic analysis of blood samples drawn at steady-state trough levels from patients receiving vigabatrin. Results: The steady-state plasma concentrations of vigabatrin showed marked interpatient variability (CV=59.5%). The mean concentration was 42 +/- 25 mu g/ml (range 11.5-102.7 mu g/ml). Nineteen patients (63%) had plasma levels between 20 and 60 mu g/ml. The plasma clearance of vigabatrin ranged from 0.24 to 1.57 ml/min/kg (mean +/- SD = 0.74 +/- 0.40 ml/min/kg), with a median value of 0.64 ml/min/kg. Concomitant treatment with carbamazepine increased the plasma clearance of vigabatrin from 0.59 ml/min/kg (monotherapy), 0.54 ml/min/kg (co-treated with phenobarbital) and 0.41 ml/min/kg (co-treated with valproic acid) to 0.92 ml/min/kg. Conclusion: Vigabatrin plasma levels show wide interpatient variability, and co-administration with carbamazepine increases vigabatrin's clearance. While there is no relationship between plasma level and anti-epileptic effect, abnormally high levels of the drug may increase toxicity.