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Author: Admin | 2025-04-28
In animal models.22 By binding presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system, pregabalin modulates the release of several excitatory neurotransmitters including glutamate, substance-P, norepinephrine, and calcitonin gene related peptide.6 In addition, pregabalin prevents the alpha2-delta subunit from being trafficked from the dorsal root ganglia to the spinal dorsal horn, which may also contribute to the mechanism of action.15 Although pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors.8 TargetActionsOrganismAVoltage-dependent calcium channel subunit alpha-2/delta-1modulatorHumansAbsorptionAfter oral dosing administered in the fasted state, pregabalin absorption is rapid, and extensive.8 Pregabalin oral bioavailability is reported to be ≥90% regardless of the dose.8 Cmax is attained within 1.5 hours after single or multiple doses, and steady state is attained within 24-48 hours with repeated administration.8,22 Both Cmax and AUC appear to be dose proportional.8Food decreases the rate of pregabalin absorption and as a result, lowers the Cmax by an estimated 25-30% and increases the Tmax to approximately 3 hours.22 However, the effect of food does not appear to impact the total absorption of pregabalin in a way that is clinically relevant. As a result, pregabalin can be administered with or without food.22Volume of distributionAfter oral administration of pregabalin, the reported apparent volume of distribution is roughly 0.5 L/kg.22 Although pregabalin is not very lipophilic, it is able to cross the blood brain barrier(BBB).16 System L transporters facilitate the transport of large amino acids across the BBB and it has been confirmed that pregabalin is a substrate.22,16 This information suggests that system L transporters are responsible for pregabalin uptake into the BBB.16In rat models, pregabalin has been shown to cross the placenta.22Protein bindingPregabalin is not plasma protein bound.8,22MetabolismLess than 2% of pregabalin is metabolized and it is excreted virtually unchanged in the urine.8,22Hover over products below to view reaction partnersRoute of eliminationPregabalin is almost exclusively eliminated in the urine.17,18Further, based on preclinical studies, pregabalin does not appear to undergo racemization to the R enantiomer in the body.11Half-lifeThe elimination half life of pregabalin is 6.3 hours.22ClearanceIn young healthy subjects the mean renal clearance is estimated to be 67.0 to 80.9 mL mL/min.22 Given pregabalin's lack of plasma protein binding, this clearance rate suggests that renal tubular reabsorption is involved.22Adverse EffectsImprove decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.ToxicityIn a systematic review that included 38 randomized controlled trials, there were 20 identified adverse effects that were significantly associated with pregabalin, most of which involve the
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