What does vigabatrin do to GABA?

Vigabatrin blocks GABA transaminase (GABA-T), the enzyme that breaks down GABA. The block is irreversible, so GABA levels rise. In people taking vigabatrin, GABA in the spinal fluid rose as the dose went up.

What drug class is vigabatrin?

Vigabatrin is an anticonvulsant (seizure medicine). It is a selective, irreversible inhibitor of the enzyme GABA transaminase.

Why is vigabatrin taken twice a day if its half-life is short?

Because vigabatrin blocks the enzyme permanently, its action lasts much longer than the drug stays in the blood. The label sets a twice-daily schedule.

Does vigabatrin interact with other seizure medicines?

It has few clinically important interactions. It mostly leaves the body unchanged and does not bind to blood proteins. One exception is phenytoin: vigabatrin lowers phenytoin levels by about 16 to 20%.

Do vigabatrin blood levels need to be checked?

Routine blood-level monitoring is not needed. Kidney function matters more, because the kidneys remove most of the drug.

Vigabatrin Mechanism of Action: How It Affects GABA

Short answer: vigabatrin is an anticonvulsant that permanently blocks GABA transaminase (GABA-T), the enzyme that breaks down GABA. With the enzyme blocked, GABA builds up.^1,2 Because the block is irreversible, the drug's effect lasts much longer than the drug itself stays in the blood.³

GABA (gamma-aminobutyric acid) is a chemical messenger in the brain that dampens nerve activity. Raising it is how vigabatrin is thought to reduce seizures. This page explains the mechanism and how the body handles the drug, in plain terms first and with numbers for clinicians after.

Drug class

Vigabatrin is an anticonvulsant, a medicine used to treat seizures. In the AHFS drug classification used on the federal NIOSH list, it is filed under "anticonvulsants, miscellaneous."⁴ More specifically, it is a selective, irreversible inhibitor of GABA-T.¹

How vigabatrin raises GABA

Without vigabatrin

With vigabatrin

GABA calms nerve activity. The enzyme GABA transaminase (GABA-T) breaks it down. Vigabatrin permanently blocks GABA-T, so GABA builds up in the brain. Simplified illustration.

GABA-T is the enzyme that breaks GABA down. Vigabatrin switches it off for good. It is selective, meaning it targets this one enzyme.¹

The effect can be measured. In people taking vigabatrin, GABA in the cerebrospinal fluid (the fluid around the brain and spinal cord) rose as the dose went up, which fits with GABA-T being blocked.²

Vigabatrin is a mix of two mirror-image forms. Only one of them, the S(+) form, is active, and the body does not convert one into the other.³

Why the effect outlasts the drug

Because vigabatrin disables the enzyme permanently, its effect does not track its blood level. In the words of one review, "the action of the drug long outlasts its presence in plasma."³ The label gives vigabatrin twice a day, even though its half-life is only about 6 to 10 hours.⁵

How the body handles vigabatrin

Absorption

Vigabatrin is absorbed almost completely when swallowed.⁵ Blood levels peak about 1 hour after a dose in children and adults, and about 2.5 hours in infants.⁵ Absorption is slower in younger patients, and in infants with spasms the amount absorbed varied by about 27% from one occasion to the next.⁶

Food lowers the peak level by about a third but does not change the total amount absorbed, so vigabatrin can be taken with or without food.^5,7 The tablet and the oral solution are bioequivalent.⁵

Distribution

Vigabatrin does not bind to proteins in the blood. Its levels rise in proportion to the dose (linear pharmacokinetics), and its volume of distribution is about 0.8 L/kg.³

Half-life by age

Half-life is the time it takes for blood levels to fall by half. For vigabatrin it is shorter in younger children:⁵

Age group	Half-life
Infants	5.7 hours
Children 3 to 9 years	6.8 hours
Children 10 to 16 years	9.5 hours
Adults	10.5 hours

From the Sabril label.⁵

Elimination through the kidneys

Vigabatrin is not broken down much by the body. Most of it leaves in the urine. In label studies, about 95% of a radiolabeled dose was found in the urine, 80% of it as unchanged vigabatrin.⁵ Earlier studies found about 65% excreted unchanged within 24 hours, and about 70% cleared by the kidneys overall.^2,3 Clearance rises and falls with kidney function.⁶

Kidney impairment

Because the kidneys do most of the work, reduced kidney function raises blood levels. In adults, exposure was about 30% higher with mild impairment, twice as high with moderate impairment and 4.5 times as high with severe impairment.⁷ The label lowers the dose by 25%, 50% or 75% depending on kidney function, for patients 2 years and older. There is no dosing information for infants with kidney impairment.⁵ In one case report, a patient with kidney failure on 3 g a day became agitated as the inactive form of the drug built up; hemodialysis removed both forms.⁸ See dosage.

Drug interactions

Vigabatrin has few clinically important interactions, and blood levels do not need routine monitoring.¹ The label notes two points:

Vigabatrin induces the liver enzyme CYP2C9, which can speed up the breakdown of some other drugs.⁵
It lowers phenytoin levels by about 16 to 20%.⁵

Tell the prescriber about every other medicine your child takes.

What this means for families

A short half-life is not a short effect. The drug's action long outlasts its time in the blood, and the label sets a twice-daily schedule.^3,5
Food does not matter. Doses can be given with or without feeds.⁷
Kidneys matter. If your child has kidney problems, the prescriber may need to adjust the dose.⁵
No blood-level tests. Vigabatrin does not need routine blood-level checks.¹ Eye checks are what is monitored. See vision loss.
Every form is the same medicine. Tablets, powder and the ready-to-use liquid all contain vigabatrin and work the same way.^5,7 See liquid vs powder, and read about its uses in infantile spasms and refractory complex partial seizures.

How vigabatrin works