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

Abstract

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.

• Authors: E Jacqz-Aigrain, M Guillonneau, E Rey, M A Macher, C Montes, C Chiron, C Loirat
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 44 Issue 2 Pg. 183-5 (Aug 1997) ISSN: 0306-5251 [Print] England
• PMID: 9278207 (Publication Type: Journal Article)

Chemical References

• Anticonvulsants
• Enzyme Inhibitors
• gamma-Aminobutyric Acid
• Vigabatrin

Topics

• Adult
• Anticonvulsants (administration & dosage, chemistry, pharmacokinetics)
• Enzyme Inhibitors (administration & dosage, chemistry, pharmacokinetics)
• Humans
• Kidney Failure, Chronic (complications, metabolism, therapy)
• Renal Replacement Therapy
• Stereoisomerism
• Tuberous Sclerosis (complications, drug therapy)
• Vigabatrin
• gamma-Aminobutyric Acid (administration & dosage, analogs & derivatives, chemistry, pharmacokinetics)