Pregabalin Versus Gabapentin

How does pregabalin compare to gabapentin in the treatment of neuropathic pain?

David F. McAuley, Pharm.D.
GlobalRPh Inc.

Pregabalin versus gabapentin:
Pregabalin, like gabapentin, is an amino acid derivative of gamma-amino butyric acid (GABA analogue).^1,2 Pregabalin is the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid, and has a similar pharmacological profile to gabapentin.¹ These agents are part of a unique class that have a high affinity to the alpha-2-delta protein in the CNS.^3,4,5 Both agents have been shown to be effective for neuropathic pain disorders, however, only prebabalin has been FDA approved for both the management of diabetic peripheral neuropathy and post herpetic neuralgia.^3,6,7

Pregabalin has been shown in studies to provide equivalent efficacy to gabapentin, however, at much lower doses.^3,5 Because lower dosages can be used to treat neuropathic pain, it is likely that pregabalin will be associated with fewer dose-related adverse events.^3,5 Part of the reason why pregabalin requires lower dosages is that it has a much higher bioavailability (90% versus 33-66%) and is rapidly absorbed (peak: 1 hr). Also, plasma concentrations increase linearly with increasing dose.³ This is not true with gabapentin. Gabapentin is slowly absorbed (peak: 3 to 4 hours post-dose) and more importantly, plasma concentrations have been found to have a non-linear relationship to increasing doses. Pregabalin has been found to have distinct pharmacokinetic advantages over gabapentin.³

Pregabalin has shown greater potency than gabapentin in pain and seizure disorders.⁶ J. Fehrenbacher et al stated that pregabalin has been shown to have greater analgesic activity in rodent models of neuropathic pain.² Further, D. Wesche et al noted that pregabalin is approximately 2.5 times more potent than gabapentin based on plasma concentrations.³

M. Vera-Llonch et al estimated analgesic outcomes in patients with painful diabetic peripheral neuropathy or post-herpetic neuralgia receiving pregabalin versus gabapentin.⁸ They developed a model to estimate the impact on analgesic outcomes of treatment with pregabalin (375 mg/day) versus gabapentin (1200 mg/day and 1800 mg/day) in a hypothetical cohort of 1,000 patients with diabetic peripheral neuropathy or post-herpetic neurolgia. Targeted outcomes included the mean number of days with no or mild pain (score<3), and days with at least a thirty to fifty percent reduction in pain intensity. The study concluded that pregabalin may provide better analgesic outcomes than gabapentin over a 12-week period.

Conclusion:
Further head-to-head trials are needed to provide further evidence supporting the use of pregabalin over gabapentin in the treatment of neuropathic pain. Current study results appear to provide early support for pregabalin based on its greater potency and pharmacokinetic superiority. Pregabalin is generally well tolerated with the most common adverse effects reported being dizziness, somnolence and peripheral edema.¹

References:

1. Frampton JE, Foster RH. Pregabalin: in the treatment of postherpetic neuralgia. Drugs. 2005;65(1):111-8; discussion 119-20.

2. Fehrenbacher JC, Taylor CP, Vasko MR. Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain. 2003 Sep;105(1-2):133-41.

3. D. Wesche, H. Bockbrader. A pharmacokinetic comparison of pregabalin and gabapentin. https://www.ampainsoc.org/abstract/2005/data/684/index.html. Accessed: June 22, 2005.

4. Lesser H, Sharma U, LaMoreaux L, Poole RM. Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. Neurology. 2004 Dec 14;63(11):2104-10.

5. Freynhagen R, Strojek K, Griesing T, Whalen E, Balkenohl M. Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of fble- and fixed-dose regimens. Pain. 2005 Jun;115(3):254-63.

6. Klasco RK (Ed): DRUGDEX® System. Thomson Micromedex, Greenwood Village, Colorado (Edition expires [Nov 2005]).

7. Pfizer Inc. FDA Approves Lyrica (Pregabalin) for Treatment of Neuropathic Pain. https://www.docguide.com/news/content.nsf/news/8525697700573E1885256F7E006DA389. Accessed: June 22, 2005.

8. M. Vera-Llonch, E. Dukes, C. Argoff, G. Oster. 24th annual scientific meeting of the american pain society, Boston, 2005. Analgesic outcomes in patients with painful diabetic neuropathy or post-herpetic neuralgia receiving pregabalin versus gabapentin. https://www.ampainsoc.org/abstract/2005/data/700/index.html. Accessed: June 22, 2005.