Gabapentin (Neurontin)

Pharmacokinetics of Gabapentin

Absorption Bioavailabiltiy of 59%. Tmax = 2-4 hours
Distribution High volume of distribution (58L), less than 3% of gabapentin is bound to plasma proteins
Metabolism Not metabolized to a significant extent in humans.
Elimination Solely renal excretion as unchanged drug, and can be
removed from plasma by hemodialysis.
Half-life 5-7 hours

Gabapentin: Cytochrome P450 Metabolism

Substrate of (Metabolized by) Not metabolized in humans
Induces -
Inhibits -
  • Gabapentin is designed as GABA analog (similar to pregabalin), which means it binds to the α2δ (alpha-2-delta) subunit of presynaptic voltage-sensitive Ca2+ channels (VSCCs), and block the release of excitatory neurotransmitters such as glutamate.
  • This changes the VSCC conformation to reduce calcium influx and thus reduce excessive stimulation of postsynaptic receptors.
  • Seizure disorders
  • Alcohol use disorder
  • Anxiety disorders, sleep disorders, pain syndromes

Dosing for Gabapentin

Starting
Titration
Maximum
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  • Gabapentin comes in oral formulation.
  • Withdrawal may occur after prolonged use of gabapentin
  • Gabapentin is an approved treatment as an adjunctive therapy in the management of epilepsy. However, it is most commonly prescribed off-label for other conditions, including anxiety, alcohol use disorder, and chronic pain.[1] Gabapentin misuse is increasing. oral, intranasal, and intravenous). Misuse can produce anxiolytic effects and a euphoria that is similar opioid misuse. Gabapentin can cause respiratory depression, physiologic dependence, and withdrawal symptoms on cessation (including diaphoresis, anxiety, confusion, and seizures).
    • Patients who are co-prescribed gabapentin and opioids are at a significantly higher risk of death compared with those prescribed opioids alone.[2]
Research