A. Sanchezalcaraz et al., PLASMA-CONCENTRATIONS OF VIGABATRIN IN EPILEPTIC PATIENTS, Journal of clinical pharmacy and therapeutics, 21(6), 1996, pp. 393-398
Objective: To measure plasma concentrations of vigabatrin in a group o
f 30 adult epileptic patients with complex partial seizures (CPS) refr
actory to conventional antiepileptic drugs. With a view to better defi
ning the drug's dose-response relationships in the presence of concomi
tant alternative antiepileptic drugs. Methods: High-performance liquid
chromatographic analysis of blood samples drawn at steady-state troug
h levels from patients receiving vigabatrin. Results: The steady-state
plasma concentrations of vigabatrin showed marked interpatient variab
ility (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 0.2
4 to 1.57 ml/min/kg (mean +/- SD = 0.74 +/- 0.40 ml/min/kg), with a me
dian value of 0.64 ml/min/kg. Concomitant treatment with carbamazepine
increased the plasma clearance of vigabatrin from 0.59 ml/min/kg (mon
otherapy), 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-ad
ministration with carbamazepine increases vigabatrin's clearance. Whil
e there is no relationship between plasma level and anti-epileptic eff
ect, abnormally high levels of the drug may increase toxicity.