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)
|