Gabapentin (gabapentin)

Gabapentin is an anticonvulsant structurally related to the inhibitory CNS neurotransmitter gamma -aminobutyric acid (GABA); the drug also possesses analgesic activity. Gabapentin enacarbil is a prodrug of gabapentin.

Gabapentin is an anticonvulsant agent structurally related to the inhibitory CNS neurotransmitter gamma-aminobutyric acid (GABA). Gabapentin enacarbil is a prodrug of gabapentin that is rapidly converted to gabapentin following oral administration; the therapeutic effects of gabapentin enacarbil are attributed to gabapentin. Although gabapentin was developed as a structural analog of GABA that would penetrate the blood-brain barrier (unlike GABA) and mimic the action of GABA at inhibitory neuronal synapses, the drug has no direct GABA-mimetic action and its precise mechanism of action has not been elucidated.

Results of some studies in animals indicate that gabapentin protects against seizure and/or tonic extensions induced by the GABA antagonists picrotoxin and bicuculline or by GABA synthesis inhibitors (e.g., 3-mercaptopropionic acid, isonicotinic acid, semicarbazide). However, gabapentin does not appear to bind to GABA receptors nor affect GABA reuptake or metabolism and does not act as a precursor of GABA or of other substances active at GABA receptors. Gabapentin also has no affinity for binding sites on common neuroreceptors (e.g., benzodiazepine; glutamate; quisqualate; kainate; strychnine-insensitive or -sensitive glycine; alpha1-, alpha2-, or beta-adrenergic; adenosine A1 or A2; cholinergic (muscarinic or nicotinic); dopamine D1 or D2; histamine H1; type 1 or 2 serotonergic (5-HT1 or 5-HT2); opiate mc, delta, or kappa) or ion channels (e.g., voltage-sensitive calcium channel sites labeled with nitrendipine or diltiazem, voltage-sensitive sodium channel sites labeled with batrachotoxinin A 20alpha-benzoate).

Conflicting results have been reported in studies of gabapentin affinity for and activity at N-methyl-d-aspartic acid (NMDA) receptors.

In animal test systems, gabapentin exhibits anticonvulsant activity similar to that of other commonly used anticonvulsant drugs. The drug protects against seizures induced in animals by electrical stimulation or pentylenetetrazole, suggesting that it may be effective in the management of tonic-clonic (grand mal) and partial seizures or absence (petit mal) seizures, respectively. However, available data in animals and humans are conflicting regarding the effect of gabapentin on EEG spike and wave activity associated with absence (petit mal) seizures.

Gabapentin also prevents seizures in some animals with congenital epilepsy and protects against audiogenic tonic extensions and clonic seizures in mice.

Although the exact mechanism by which gabapentin exerts its analgesic effects is not known, the drug has been shown to prevent allodynia (pain-related behavior in response to normally innocuous stimuli) and hyperalgesia (exaggerated response to painful stimuli) in several models of neuropathic pain. Gabapentin also has been shown to decrease pain-related responses after peripheral inflammation in animals; however, the drug has not altered immediate pain-related behaviors. The clinical relevance of these findings is not known.

In vitro studies demonstrate that gabapentin binds to the alpha2delta subunit of voltage-activated calcium channels; however, the clinical importance of this effect is not known.

The pharmacokinetic properties of gabapentin vary based on the specific formulation of the drug. (See Dosage and Administration: Administration.) Following oral administration, gabapentin is absorbed principally in the proximal small intestine via a saturable L-amino acid transport system; as a result, the bioavailability of the drug decreases with increasing doses. Gabapentin gastroretentive tablets are specifically formulated to swell upon contact with gastric fluid to a size that promotes gastric retention for approximately 8-10 hours when taken with a meal; this allows for gradual and slow release of the drug to the proximal small intestine, its principal site of absorption. Following administration of gabapentin gastroretentive tablets in healthy individuals, time to peak plasma concentrations of the drug was increased (about 4-6 hours longer), peak plasma concentrations were increased, and systemic exposure was decreased relative to conventional (immediate-release) gabapentin.

Gabapentin enacarbil, a prodrug of gabapentin, is rapidly and efficiently converted to gabapentin by first-pass hydrolysis following oral administration. Unlike gabapentin, gabapentin enacarbil is absorbed via high-capacity transporters throughout the GI tract and is not affected by saturable absorption; this improves bioavailability of the drug and allows for dose-proportional exposure. Food has only a minimal effect on the pharmacokinetics of conventional (immediate-release) formulations of gabapentin, but increases the bioavailability of gabapentin gastroretentive tablets.

Administration of gabapentin enacarbil extended-release tablets with food also increases systemic exposure of the drug compared with exposure under fasted conditions. Gabapentin does not bind to plasma proteins, is not appreciably metabolized, does not induce hepatic enzyme activity, and does not appear to alter the pharmacokinetics of commonly used anticonvulsant drugs (e.g., carbamazepine, phenytoin, valproate, phenobarbital, diazepam) or oral contraceptives. In addition, the pharmacokinetics of gabapentin are not altered substantially by concomitant administration of other anticonvulsant drugs.

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information.

The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Conventional (immediate-release) preparations of gabapentin are used in the management of seizure disorders. Conventional preparations also may be used in the treatment of postherpetic neuralgia (PHN). Gabapentin also is commercially available as a gastroretentive tablet formulation (Gralise(R)) for once-daily administration in the treatment of PHN.

Because of differences in pharmacokinetic properties, gabapentin gastroretentive tablets are not interchangeable with other gabapentin preparations.

Generic name: gabapentin
Pronunciation: (gab-uh-PEN-tin)

The following indications are listed for Gabapentin:

• Partial Epilepsy Treatment Adjunct
• Postherpetic Neuralgia

Also known as: Partial Onset Seizures Treatment Adjunct, Partial Seizures Treatment Adjunct, Post Herpetic Neuralgia, Postherpetic Neurodynia.

No ICD codes are available for this drug.