indication

For the management of postherpetic neuralgia in adults and as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients over 12 years of age with epilepsy.

pharmacology

Gabapentin, an analog of GABA, is used as an anticonvulsant to treat partial seizures, amyotrophic lateral sclerosis (ALS), and painful neuropathies. Potential uses include monotherapy of refractory partial seizure disorders, and treatment of spasticity in multiple sclerosis, tremor. mood disorders, and attenuation of disruptive behaviors in dementia. Gabapentin has high lipid solubility, is not metabolized by the liver, has no protein binding, and doesn't possess the usual drug interactions.

mechanism of action

Gabapentin interacts with cortical neurons at auxillary subunits of voltage-sensitive calcium channels. Gabapentin increases the synaptic concentration of GABA, enhances GABA responses at non-synaptic sites in neuronal tissues, and reduces the release of mono-amine neurotransmitters. One of the mechanisms implicated in this effect of gabapentin is the reduction of the axon excitability measured as an amplitude change of the presynaptic fibre volley (FV) in the CA1 area of the hippocampus. This is mediated through its binding to presynaptic NMDA receptors. Other studies have shown that the antihyperalgesic and antiallodynic effects of gabapentin are mediated by the descending noradrenergic system, resulting in the activation of spinal alpha2-adrenergic receptors. Gabapentin has also been shown to bind and activate the adenosine A1 receptor.

toxicity

Symptoms of overdose include ataxia, labored breathing, ptosis, sedation, hypoactivity, and excitation.

biotransformation

All pharmacological actions following gabapentin administration are due to the activity of the parent compound; gabapentin is not appreciably metabolized in humans.

absorption

Rapid. Absorbed in part by the L-amino acid transport system, which is a carrier-mediated, saturable transport system; as the dose increases, bioavailability decreases. Bioavailability ranges from approximately 60% for a 900 mg dose per day to approximately 27% for a 4800 milligram dose per day. Food has a slight effect on the rate and extent of absorption of gabapentin (14% increase in AUC).

half life

5-7 hours

route of elimination

Gabapentin is eliminated from the systemic circulation by renal excretion as unchanged drug. Gabapentin is not appreciably metabolized in humans.

drug interactions

Ethotoin: Increases the effect of hydantoin

Fosphenytoin: Gabapentin may increase the effect of fosphenytoin.

Mephenytoin: Increases the effect of hydantoin

Phenytoin: Gabapentin may increase the therapeutic and adverse effects of phenytoin.

Triprolidine: The CNS depressants, Triprolidine and Gabapentin, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.