Pebarin Mechanism of Action

Pharmacology: Pharmacodynamics: Pregabalin binds with high affinity to the alpha-2-delta site, an auxiliary subunit of voltage-gated calcium channels in CNS tissues. Binding to the alpha-2-delta may be involved in analgesic and anticonvulsant effects. In vitro, Pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function.
Pregabalin is structurally related to the gamma–aminobutyric acid (GABA). However, it does not bind to GABA_A, GABA_B or benzodiazepine receptors.
Pharmacokinetics: Absorption: Pregabalin is well absorbed after oral administration. Following oral administration of Pregabalin capsules under fasting conditions, peak plasma concentrations occur within 1.5 hours. Pregabalin bioavailability is about 90% or more and is independent of dose. Following single dose of 25 to 300 mg and multiple dose of 75 to 900 mg/day administration, maximum plasma concentration (C_max) and area under the curve (AUC) values increase linearly. Following repeated administration, steady state is achieved within 24 to 48 hours. The rate of Pregabalin absorption is decreased when given with food, resulting in a decrease in C_max of approximately 25% to 30% and an increase in time of maximal concentration (T_max) to approximately 3 hours. However, administration of Pregabalin with food has no clinically relevant effect on the total absorption of Pregabalin. Therefore, Pregabalin can be taken with or without food.
Distribution: Pregabalin does not bind to plasma proteins. The apparent volume 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. Although there are no data in humans, Pregabalin crossed the blood brain barrier in mice, rats, and monkeys. In addition, Pregabalin crosses placenta in rats and was present in the milk of lactating rats.
Metabolism: Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabeled Pregabalin, approximately 90% of the administered dose recovered in the urine was unchanged Pregabalin. The N-methylated derivative of Pregabalin, the major metabolite of pregabalin found in urine, accounted for 0.9% of the dose. In preclinical studies, Pregabalin (S-enantiomer) did not undergo racemization to the R-enantiomer in mice, rats, rabbits, or monkeys.
Excretion: 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 healthy renal function. Mean renal clearance was estimated to be 67 to 80.9 mL/min in young, healthy subjects. Because Pregabalin is not bound to plasma proteins, this clearance rate indicates that renal tubular reabsorption is involved.