Brands, Medical Use, Clinical Data
- Anti-Anxiety Agents
- Antimanic Agents
- Antiparkinson Agents
- Calcium Channel Blockers
- Excitatory Amino Acid Antagonists
- Tablet (oral)
- Solution (oral)
Brands / Synonyms
Aclonium; Gababentin; Gabapentin [Usan:Ban:Inn]; Gabapentine; Gabapentine [Inn-French]; Gabapentino [Inn-Spanish]; Gabapentino [Spanish]; Gabapentinum [Inn-Latin]; Gabapetin; Horizant; Neurontin; Novo-Gabapentin
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.
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.
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).
Symptoms of overdose include ataxia, labored breathing, ptosis, sedation, hypoactivity, and excitation.
Biotrnasformation / Drug Metabolism
All pharmacological actions following gabapentin administration are due to the activity of the parent compound; gabapentin is not appreciably metabolized in humans.
NeurontinÒ is contraindicated in patients who have demonstrated hypersensitivity to
the drug or its ingredients.
In vitro studies were conducted to investigate the potential of gabapentin to inhibit the major cytochrome
P450 enzymes (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) that mediate drug and xenobiotic
metabolism using isoform selective marker substrates and human liver microsomal preparations. Only at the highest
concentration tested (171 μg/mL; 1 mM) was a slight degree of inhibition (14%-30%) of
isoform CYP2A6 observed. No inhibition of any of the other isoforms tested was observed at gabapentin concentrations
up to 171 mg/mL (approximately 15 times the Cmax at 3600 mg/day).
Gabapentin is not appreciably metabolized nor does it interfere with the metabolism of commonly coadministered
The drug interaction data described in this section were obtained from studies involving healthy adults and adult
patients with epilepsy.
Phenytoin: In a single (400 mg) and multiple dose (400 mg TID) study of NeurontinÒ in epileptic patients (N=8) maintained on phenytoin monotherapy for at least 2 months,
gabapentin had no effect on the steady-state trough plasma concentrations of phenytoin and phenytoin had no effect on
Carbamazepine: Steady-state trough plasma carbamazepine and carbamazepine 10, 11 epoxide concentrations
were not affected by concomitant gabapentin (400 mg TID; N=12) administration. Likewise, gabapentin pharmacokinetics
were unaltered by carbamazepine administration.
Valproic Acid: The mean steady-state trough serum valproic acid concentrations prior to and during
concomitant gabapentin administration (400 mg TID; N=17) were not different and neither were gabapentin
pharmacokinetic parameters affected by valproic acid.
Phenobarbital: Estimates of steady-state pharmacokinetic parameters for phenobarbital or gabapentin (300 mg
TID; N=12) are identical whether the drugs are administered alone or together.
Naproxen: Coadministration (N=18) of naproxen sodium capsules (250 mg) with NeurontinÒ (125 mg) appears to increase the amount of gabapentin absorbed by 12% to 15%. Gabapentin
had no effect on naproxen pharmacokinetic parameters. These doses are lower than the therapeutic doses for both
drugs. The magnitude of interaction within the recommended dose ranges of either drug is not known.
Hydrocodone: Coadministration of NeurontinÒ (125 to 500 mg;
N=48) decreases hydrocodone (10 mg; N=50) Cmax and AUC values in a dose-dependent manner relative to
administration of hydrocodone alone; Cmax and AUC values are 3% to 4% lower, respectively, after
administration of 125 mg NeurontinÒ and 21% to 22% lower, respectively,
after administration of 500 mg NeurontinÒ. The mechanism for this
interaction is unknown. Hydrocodone increases gabapentin AUC values by 14%. The magnitude of interaction at other
doses is not known.
Morphine: A literature article reported that when a 60-mg controlled-release morphine capsule was
administered 2 hours prior to a 600-mg NeurontinÒ capsule (N=12), mean
gabapentin AUC increased by 44% compared to gabapentin administered without morphine. Morphine pharmacokinetic
parameter values were not affected by administration of NeurontinÒ 2 hours
after morphine. The magnitude of interaction at other doses is not known.
Cimetidine: In the presence of cimetidine at 300 mg QID (N=12) the mean apparent oral clearance of
gabapentin fell by 14% and creatinine clearance fell by 10%. Thus cimetidine appeared to alter the renal excretion of
both gabapentin and creatinine, an endogenous marker of renal function. This small decrease in excretion of
gabapentin by cimetidine is not expected to be of clinical importance. The effect of gabapentin on cimetidine was not
Oral Contraceptive: Based on AUC and half-life, multiple-dose pharmacokinetic profiles of norethindrone and
ethinyl estradiol following administration of tablets containing 2.5 mg of norethindrone acetate and 50 mcg of
ethinyl estradiol were similar with and without coadministration of gabapentin (400 mg TID; N=13). The
Cmax of norethindrone was 13% higher when it was coadministered with gabapentin; this interaction is not
expected to be of clinical importance.
Antacid (MaaloxÒ): Maalox reduced the bioavailability of
gabapentin (N=16) by about 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2
hours after Maalox. It is recommended that gabapentin be taken at least 2 hours following Maalox administration.
Effect of Probenecid: Probenecid is a blocker of renal tubular secretion. Gabapentin pharmacokinetic
parameters without and with probenecid were comparable. This indicates that gabapentin does not undergo renal tubular
secretion by the pathway that is blocked by probenecid.
Drug/Laboratory Tests Interactions
Because false positive readings were reported with the Ames N-Multistix SGÒ dipstick test for urinary protein when gabapentin was added to other antiepileptic drugs,
the more specific sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine