Pregalin Mechanism of Action

Pharmacology: Pharmacodynamics: Binds to alpha₂-delta subunit of voltage-gated calcium channels within the CNS and modulates calcium influx at the nerve terminals, thereby inhibiting excitatory neurotransmitter release including glutamate, norepinephrine (noradrenaline), serotonin, dopamine, substance P, and calcitonin gene-related peptide. Although structurally related to GABA, it does not bind to GABA or benzodiazepine receptors. Exerts antinociceptive and anticonvulsant activity. Pregabalin may also affect descending noradrenergic and serotonergic pain transmission pathways from the brainstem to the spinal cord.
Pharmacokinetics: Absorption/Distribution: Pregabalin is well absorbed after oral administration. Following oral administration of pregabalin under fasting conditions, peak plasma concentrations (Cmax) occur within 1.5 hours. Steady state is achieved within 24 to 48 hours.
Pregabalin does not bind to plasma proteins. The distribution of pregabalin following oral administration is approximately 0.5 L/kg. Pregabalin is a substrate for system L transporter, which is responsible for the transport of large amino acids across the blood-brain barrier.
Metabolism/Excretion: Pregabalin undergoes negligible metabolism in humans. Approximately 90% of the administered dose was recovered in the urine as unchanged pregabalin.
Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug, with a mean elimination half-life of 6.3 hours in subjects with normal renal function. Because pregabalin is not bound to plasma proteins, this clearance rate indicates that renal tubular reabsorption is involved.
Breastfeeding Women: Small amounts of pregabalin have been detected in the breast milk. In a pharmacokinetic study, pregabalin concentrations in plasma and breast milk of 10 lactating women (at least 12 weeks postpartum) taking pregabalin 150 mg oral capsules every 12 hours (a total of 4 doses) were evaluated. Pregabalin concentrations in breast milk were about 76% of those in maternal plasma and the estimated average daily infant dose of pregabalin from breast milk was about 7% of the maternal dose. The effect of pregabalin on milk production and breasted infant were not evaluated.