Pharmacokinetics of the S(+) and R(−) enantiomers of vigabatrin during chronic dosing in a patient with renal failure

Aims To study the pharmacokinetics of vigabatrin in a patient affected with tuberous sclerosis who developed major agitation and aggression, while receiving vigabatrin orally (1.5  g every 12  h) and in whom impaired renal function was diagnosed.
Methods The patient received vigabatrin (0.5  g  day⁻¹ ). A pharmacokinetic study of the S(+) and R(−) enantiomers of vigabatrin was performed before and during dialysis. Plasma concentrations were measured at 0, 1, 2, 3, 4, 6, 12, 18 and 24  h by a specific GCMS assay.
Results Before dialysis, the maximum and minimun plasma concentrations of vigabatrin at steady-state were lower for the S(+) than for the R(−) enantiomer, while the apparent oral clearance was higher for the S(+) than for the R(−) enantiomer (2.97 vs 0.48 l  h⁻¹ ). In addition, the haemodialysis clearance was similar for the two enantiomers (4.96 vs 5.15 l  h⁻¹ ).
Conclusions Vigabatrin is an irreversible inhibitor of GABA-transaminase, effective in the treatment of drug-resistant epilepsy and reported to be eliminated unchanged by renal excretion. Although vigabatrin is known to have stereoselective kinetics, the difference in plasma dry concentrations and pharmacokinetics of the S(+) and R(−) enantiomers that we observed during long term administration at high doses in a patient with impaired renal function, has not been reported before. The question remains of the potential toxicity of the high levels of the R(−) enantiomer.