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.

Dosing for Gabapentin

  • Gabapentin comes in oral formulation.
  • Gabapentin can also cause myoclonus (especially in the setting of acute kidney injuries when gabapentin is not able to be cleared).[1]
  • 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.[2]
  • 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.[3]