Effect of vigabatrin on epilepsy in mentally retarded patients

Matilainen, Riitta; Pitkänen, A.; Ruutiainen, T; Mervaala, Esa; Sarlund, H.; Riekkinen, Paavo

doi:10.1212/wnl.38.5.743

Cited by 59 publications

(20 citation statements)

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“…Vigabatrin had no effect on plasma concentrations of carbamazepine, valproic acid, phenobarbital, clonazepam, clobazam, ethosuximide and oxcarbazepine (Cocito et al 1989;Gram et al 1985;Loiseau et al 1986;Luna et al 1989;Matilainen et al 1988). …”

Section: Drug Interactionsmentioning

confidence: 93%

Vigabatrin

Rey

Pons

Olivé

1992

Clinical Pharmacokinetics

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Vigabatrin is a structural analogue of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). It is supplied as a racemic mixture, with the S(+) enantiomer possessing pharmacological activity. [R,S]-Vigabatrin plasma concentrations can be estimated using high-performance liquid chromatographic methods. Only gas chromatography-mass spectrometry methods allow quantification of the S(+) and R(-) enantiomers. Vigabatrin was rapidly absorbed reaching peak concentrations within 1 to 2h. Area under plasma concentration-time curves indicated dose-linear pharmacokinetics. There was no effect of food on the absorption of vigabatrin. The absorption characteristics of the enantiomers were similar to those of the [R,S]-vigabatrin. No chiral inversion was detected after administration of the pure S(+) enantiomer. Vigabatrin is not protein bound. The apparent volume of distribution of [R,S]-vigabatrin was approximately 0.8 L/kg. Despite the lack of protein binding, cerebrospinal concentrations of the [R,S]-vigabatrin were only 10% of the plasma concentration 6h after a single oral dose. The half-life of [R,S]-vigabatrin was between 5.3 and 7.4h, the half-life of the enantiomers were 7.5 and 8.1h for the S(+) and the R(-) forms, respectively. The major route of elimination was renal excretion; urinary recovery of the [R,S]-vigabatrin was close to 70%. Pharmacokinetic studies in epileptic children did not show any significant effect of maturation on the disposition of the S(+) enantiomer: the half-life and the renal clearance were similar to adult values. Data suggest a lower bioavailability in children. In adults with epilepsy, the half-life of the [R,S]-vigabatrin ranged from 4.2 and 5.6h, similar to that measured in healthy adults. In elderly nonepileptic volunteers the pharmacokinetics of the enantiomers of vigabatrin showed delayed absorption, a major increase in peak concentration and a prolonged half-life. These changes were attributed to decreased renal clearance of vigabatrin. A nonlinear relationship between renal clearance and creatinine clearance was suggested. Vigabatrin caused a 20% fall in plasma phenytoin concentrations, the mechanism of which has not been elucidated. There were no other interactions with most concurrently administered anticonvulsants. The usual dosage of vigabatrin as add-on treatment in adults is 2 to 4g daily. Higher dosages up to 80 mg/kg daily were required in children. A dosage adjustment was recommended in any patient with decreased renal clearance. Although anticonvulsant effects were clearly related to dosage, monitoring of plasma concentrations of vigabatrin as a guide to dosage is unlikely to be of as much value as with other antiepileptic drugs. The action of the drug long outlasts its presence in plasma.

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Section: Drug Interactionsmentioning

confidence: 93%

Vigabatrin

Rey

Pons

Olivé

1992

Clinical Pharmacokinetics

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“…With the exception of decreased hemoglobin levels noted in several children receiving VGB (38) and decreased granulocytes observed in a few adult patients (39), no clinically significant laboratory changes have been reported with VGB (28). Serum levels of liver transaminase are reported to be reduced in some patients during VGB administration (40), but these have not been associated with hepatic or renal dysfunction (28).…”

Section: Ltgmentioning

confidence: 99%

Overview of the Safety of Newer Antiepileptic Drugs

Shorvon

Stefan

1997

Epilepsia

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Summary: Standard antiepileptic drugs (AEDs) are associated with a wide variety of acute and chronic adverse events and with many interactions with each other and with nonAEDs that complicate patient management. The safety and interaction profiles of the newer AEDs have also been intensively studied. Safety data are available for six of the newer AEDs, lamotrigine (LTG), vigabatrin (VGB), gabapentin (GBP), tiagabine (TGB), felbamate (FBM), and topiramate (TPM). The potential for the most recently developed AEDs for producing rare idiosyncratic reactions cannot be ascertained until additional patient exposures have been reported from careful postmarketing surveillance.

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confidence: 99%

“…Several groups have reported changes in subjectively assessed aggression, irritability, and other mood components, 3 20 21 but other studies have shown no effect of vigabatrin on mood'819 and an overall improvement in quality of life and subjective wellbeing as assessed by questionnaire. '8 [21][22][23] Methods PATIENTS AND PROCEDURES Forty five outpatients with partial seizures refractory to optimal antiepileptic drug treatment were studied. Patients had shown an ability to keep an accurate seizure diary distinguishing between simple partial seizures, complex partial seizures, and secondary generalised seizures.…”

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Effects of vigabatrin on partial seizures and cognitive function.

Grünewald

Thompson

Corcoran

et al. 1994

Journal of Neurology, Neurosurgery & Psychiatry

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In comparison with the baseline period, vigabatrin treatment was associated with a significant reduction in median complex partial seizure frequency four to 12 and 12 to 20 weeks after commencing vigabatrin (-66% and -69% in the vigabatrin group, + 50% and + 25% in the placebo group). Ten of 20 patients on vigabatrin and four of 23 on placebo showed a > 50% reduction in complex partial seizure frequency in the last eight weeks of double blind treatment. At least 60% of responders had maintained the response to vigabatrin when assessed during the open phase of the trial at 44 weeks. Two patients discontinued vigabatrin because of depression, which resolved on drug withdrawal.

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Effect of vigabatrin on epilepsy in mentally retarded patients

Cited by 59 publications

References 1 publication

Vigabatrin

Vigabatrin

Overview of the Safety of Newer Antiepileptic Drugs

Effects of vigabatrin on partial seizures and cognitive function.

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