Pharmacokinetic and pharmacodynamic profile of pregabalin and its role in the treatment of epilepsy

Abstract

Introduction: Pregabalin, the S-enantiomer of 3-aminomethyl-5-methylhaxanoic acid, is a second-generation antiepileptic drug (AED) developed after gabapentin with improved pharmacokinetic and pharmacodynamics properties. Pregabalin has a linear uptake without transporter saturation at therapeutic dosages, high bioavailability with rapid absorption independent of food intake. There is no binding to plasma proteins, and more than 90% of the drug is renally excreted, mostly without prior metabolization. Binding to the α₂δ subunit of P/Q-type voltage-gated calcium channels, pregabalin is thought to exert its antiepileptic potency by modulating calcium channel traffic and physiology thus reducing the presynaptic calcium influx and subsequent neurotransmitter release.

Areas covered: The article presents the pharmacokinetics and pharmacodynamics of pregabalin as well as its efficacy and tolerability in clinical trials. The article also looks at its clinical application as a combination therapy with particular respect to its pharmacokinetic profile.

Expert opinion: The higher intrinsic potency of pregabalin compared to gabapentin is associated with an increased antiepileptic efficacy both in animal models of epilepsy and in clinical applications. In randomized add-on trials, seizure reduction compares favorably with other second-generation AED. Reliable absorption, absence of protein binding and hepatic metabolism make treatment reliable as does the absence of interactions with coadministered drugs. The rapid onset of action with significant antiepileptic effects at dosages of 150 – 600 mg/day makes pregabalin an option in patients with high seizure frequency. Whereas weight gain in some patients can cause acceptance problems, favorable effects on mood offer advantages in many patients with chronic epilepsy and psychiatric comorbidities.

Keywords::

• antiepileptic drug
• calcium channels
• clinical trials
• focal epilepsy
• gabapentin
• pharmacodynamics
• pharmacokinetics
• pregabalin

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