Pregabalin in epilepsy

Pregabalin is an antiepileptic medication that works by binding to alpha 2 delta subunit of the voltage-dependent calcium channels present in presynaptic neurons

• its pharmacokinetic advantages include rapid and almost complete absorption, lack of protein binding, linear kinetics, absence of enzyme induction, and absence of interactions with other drugs
  • like gabapentin it works by binding to alpha 2 delta subunit of the P/Q-type voltage-sensitive Ca2+ channels (VSCC) which are present in presynaptic neurons
  • pregabalin is structurally related to both the neurotransmitter gamma- aminobutyric acid (GABA), and the older antiepileptic drug, gabapentin
  • the primary mechanism underlying the pharmacological action of pregabalin does not appear to involve the GABA system
    • in particular, pregabalin does not bind to GABA-A, GABA-B, or benzodiazepine receptors
      • pregabalin is neither metabolically converted to GABA or to a GABA agonist, nor does it have any effect on the uptake or degradation of GABA.
  • does not block calcium channels rather it modulates calcium channels
  • is rapidly and completely absorbed after oral dosing in the fasting state (bioavailability is >90%) (1)
    • absorption is not dose-dependent
    • is not protein-bound
    • maximal plasma concentrations are reached in 1 hour after single or multiple doses, and steady state is achieved within 24 to 48 hours after repeated administration
      • therefore, pregabalin can be taken with or without food
        
        
• is approved in multiple countries worldwide as an add-on therapy for focal onset seizures in adult and paediatric populations (2)
  
  
• a systematic review found pregabalin significantly more effective than placebo at producing a 50% or greater seizure reduction and seizure freedom with increasing effectiveness at 600 mg doses, although with tolerability issues (2)

Reference:

• Arain AM. Pregabalin in the management of partial epilepsy. Neuropsychiatr Dis Treat. 2009;5:407-413. doi:10.2147/ndt.s3850
• Panebianco M, Bresnahan R, Marson AG. Pregabalin add -on for drug - resistant focal epilepsy. Cochrane Database of Systematic Reviews 2022, Issue 3. Art. No.: CD005612. DOI: 10.1002/14651858.CD005612.pub5.