A Comparison of the Pharmacokinetics and Pharmacodynamics of Pregabalin and Gabapentin

Abstract

Pregabalin and gabapentin share a similar mechanism of action, inhibiting calcium influx and subsequent release of excitatory neurotransmitters; however, the compounds differ in their pharmacokinetic and pharmacodynamic characteristics. Gabapentin is absorbed slowly after oral administration, with maximum plasma concentrations attained within 3-4 hours. Orally administered gabapentin exhibits saturable absorption--a nonlinear (zero-order) process--making its pharmacokinetics less predictable. Plasma concentrations of gabapentin do not increase proportionally with increasing dose. In contrast, orally administered pregabalin is absorbed more rapidly, with maximum plasma concentrations attained within 1 hour. Absorption is linear (first order), with plasma concentrations increasing proportionately with increasing dose. The absolute bioavailability of gabapentin drops from 60% to 33% as the dosage increases from 900 to 3600 mg/day, while the absolute bioavailability of pregabalin remains at > or = 90% irrespective of the dosage. Both drugs can be given without regard to meals. Neither drug binds to plasma proteins. Neither drug is metabolized by nor inhibits hepatic enzymes that are responsible for the metabolism of other drugs. Both drugs are excreted renally, with elimination half-lives of approximately 6 hours. Pregabalin and gabapentin both show dose-response relationships in the treatment of postherpetic neuralgia and partial seizures. For neuropathic pain, a pregabalin dosage of 450 mg/day appears to reduce pain comparably to the predicted maximum effect of gabapentin. As an antiepileptic, pregabalin may be more effective than gabapentin, on the basis of the magnitude of the reduction in the seizure frequency. In conclusion, pregabalin appears to have some distinct pharmacokinetic advantages over gabapentin that may translate into an improved pharmacodynamic effect.

Misuse and Abuse of Pregabalin and Gabapentin: Cause for Concern?

“…This may be considered an observation that is in apparent contrast with gabapentinoids, similar to benzodiazepines, being GABA analogues only [26]. With a relatively short half-life of about 6 h, gabapentinoids are mostly ([98 %) excreted unchanged in the urine [15], with a urine specimen being positive for pregabalin for up to 5-6 days after intake in subjects with normal renal function [2].…”

“…Furthermore, orally administered pregabalin is absorbed more rapidly than gabapentin, with maximum plasma concentrations attained within 1 h as opposed to 3-4 h [15]. Indeed, the absolute bioavailability of gabapentin drops from 60 to 33 % as the dosage increases from 900 to 3,600 mg/day, while the absolute bioavailability of pregabalin remains at C90 % irrespective of the dosage [15].…”

Comparative efficacious study between preoperative pregabalin and gabapentin on postoperative pain in abdominal hysterectomy: an institutional experience

“…14 These drugs are only available for oral administration and the absorption of gabapentin is slow and limited by active transport in the gastrointestinal tract. 15,16 Plasma concentrations of gabapentin do not increase proportionally with increasing dose (non-linear absorption). In contrast, pregabalin absorption is more rapid and without a ceiling of amount absorbed.…”

In vivo imaging reveals that pregabalin inhibits cortical spreading depression and propagation to subcortical brain structures

“…Although, initial studies suggested that gabapentin may be effective in the treatment of migraine, it has since been shown to have only nominal potency in migraineurs (19). Pregabalin (Lyrica) displays more linear kinetics and a longer half-life than gabapentin (20) and has shown initially encouraging results as a potential treatment for migraine Significance Spreading depression is proposed to underlie migraine with aura, a type of debilitating headache for which few pharmacological treatments are available. The pain drug pregabalin has demonstrated initial promising results for the treatment of migraine in the clinic.…”