| 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. |
| Pharmacodynamics |
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. |
| 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). |
| Volume of distribution |
|
| Protein binding |
Less than 3% of gabapentin circulates bound to plasma protein. |
| Metabolism |
All pharmacological actions following gabapentin administration
are due to the activity of the parent compound; gabapentin is not
appreciably metabolized in humans. |
| Route of elimination |
Gabapentin is eliminated from the systemic circulation by renal excretion as unchanged drug.
Gabapentin is not appreciably metabolized in humans. |
| Half life |
5-7 hours |
| Clearance |
|
| Toxicity |
Symptoms of overdose include ataxia, labored breathing, ptosis, sedation, hypoactivity, and excitation. |
