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Pregabalin

In the Treatment of Postherpetic Neuralgia

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Abstract

▴ Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid, has a similar pharmacological profile to that of its developmental predecessor gabapentin, but showed greater analgesic activity in rodent models of neuropathic pain.

▴ The exact mechanism of action of pregabalin is unclear, although it may reduce excitatory neurotransmitter release by binding to the α2-gd protein subunit of voltage-gated calcium channels.

▴ Oral pregabalin 150–600 mg/day, administered twice or three times daily, was superior to placebo in relieving pain and improving pain-related sleep interference in three randomised, double-blind, placebo-controlled, multicentre studies of 8–13 weeks’ duration in a total of 776 evaluable patients with postherpetic neuralgia (PHN).

▴ Weekly mean pain scores (primary endpoint; assessed in all three studies) and weekly mean sleep interference scores (assessed in two studies) were significantly improved at 1 week. In two studies, significant improvements in daily mean pain scores were apparent on the first or second day of treatment with pregabalin administered three times daily.

▴ Pregabalin was generally well tolerated when force-titrated over 1 week to fixed dosages (maximum 600 mg/day) in clinical trials that enrolled mostly elderly PHN patients. Dizziness, somnolence and peripheral oedema of mild-to-moderate intensity were the most common adverse events.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Kanazi GE, Johnson RW, Dworkin RH. Treatment of postherpetic neuralgia: an update. Drugs 2000 May; 59(5): 1113–26

    Article  PubMed  CAS  Google Scholar 

  2. Dworkin RH, Backonja M, Rowbotham MC, et al. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol 2003 Nov; 60(11): 1524–34

    Article  PubMed  Google Scholar 

  3. Dubinsky RM, Rabbani H, El-Chami Z, et al. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2004; 63: 959–65

    Article  PubMed  CAS  Google Scholar 

  4. Spruce MC, Potter J, Coppini DV. The pathogenesis and management of painful diabetic neuropathy: a review. Diabet Med 2003; 20(2): 88–98

    Article  PubMed  CAS  Google Scholar 

  5. Huckle. Pregabalin (Pfizer). Curr Opin Investig Drugs 2004; 5(1): 82–9

    PubMed  CAS  Google Scholar 

  6. Pfizer Inc. Pfizer statement on regulatory status of Lyrica [online]. Available from URL: http://www.pfizer.com/are/news_releases/2004pr/mn_2004_0902.html [Accessed 2004 Sep 28]

  7. Lauria-Horner BA, Pohl RB. Pregabalin: a new anxiolytic. Expert Opinon Investig Drugs 2003; 12(4): 663–72

    Article  CAS  Google Scholar 

  8. Bryans JS, Wustrow DJ. 3-Substituted GABA analogs with central nervous system activity: a review. Med Res Rev 1999; 19: 149–77

    Article  PubMed  CAS  Google Scholar 

  9. Nozaki-Taguchi N, Chaplan SR, Higuera ES, et al. Vincristine-induced allodynia in the rat. Pain 2001 Jul; 93(1): 69–76

    Article  PubMed  CAS  Google Scholar 

  10. Field MJ, McCleary S, Hughes J, et al. Gabapentin and pregabalin, but not morphine and amitriptyline, block both static and dynamic components of mechanical allodynia induced by streptozocin in the rat. Pain 1999 Mar; 80(1–2): 391–8

    Article  PubMed  CAS  Google Scholar 

  11. Field MJ, Bramwell S, Hughes J, et al. Detection of static and dynamic components of mechanical allodynia in rat models of neuropathic pain: are they signalled by distinct primary sensory neurones? Pain 1999 Nov; 83(2): 303–11

    Article  PubMed  CAS  Google Scholar 

  12. Wallin J, Cui JG, Yakhnitsa V, et al. Gabapentin and pregabalin suppress tactile allodynia and potentiate spinal cord stimulation in a model of neuropathy. Eur J Pain 2002; 6(4): 261–72

    Article  PubMed  CAS  Google Scholar 

  13. Chen SR, Xu Z, Pan HL. Stereospecific effect of pregabalin on ectopic afferent discharges and neuropathic pain induced by sciatic nerve ligation in rats. Anesthesiology 2001 Dec; 95(6): 1473–9

    Article  PubMed  CAS  Google Scholar 

  14. Field MJ, Oles RJ, Lewis AS, et al. Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of selective antihyperalgesic agents. Br J Pharmacol 1997 Aug; 121(8): 1513–22

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Hurley RW, Chatterjea D, Rose Feng M, et al. Gabapentin and pregabalin can interact synergistically with naproxen to produce antihyperalgesia. Anesthesiology 2002 Nov; 97(5): 1263–73

    Article  PubMed  CAS  Google Scholar 

  16. Partridge BJ, Chaplan SR, Sakamoto E, et al. Characterisation of the effects of gabapentin and 3-isobutyl-gamma-aminobutyric acid on substance P-induced thermal hyperalgesia. Anesthesiology 1998 Jan; 88(1): 196–205

    Article  PubMed  CAS  Google Scholar 

  17. Jun JH, Yaksh TL. The effect of intrathecal gabapentin and 3-isobutyl gamma-aminobutyric acid on the hyperalgesia observed after thermal injury in the rat. Anesth Analg 1998 Feb; 86(2): 348–54

    PubMed  CAS  Google Scholar 

  18. Jones DL, Sorkin LS. Systemic gabapentin and S(+)-3-isobutyl-gamma-aminobutyric acid block secondary hyperalgesia. Brain Res 1998 Nov 9; 810(1–2): 93–9

    Article  PubMed  CAS  Google Scholar 

  19. Field MJ, Holloman EF, McCleary S, et al. Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain. J Pharmacol Exp Ther 1997 Sep; 282(3): 1242–6

    PubMed  CAS  Google Scholar 

  20. Bialer M, Johannessen SI, Kupferberg HJ, et al. Progress report on new antiepileptic drugs: a summary of the fifth Eilat conference (EILAT V). Epilepsy Res 2001; 43: 11–58

    Article  PubMed  CAS  Google Scholar 

  21. Fink K, Dooley DJ, Meder WP, et al. Inhibition of neuronal Ca(2+) influx by gabapentin and pregabalin in the human neocortex. Neuropharmacology 2002 Feb; 42(2): 229–36

    Article  PubMed  CAS  Google Scholar 

  22. Dooley DJ, Mieske CA, Borosky SA. Inhibition of K(+)-evoked glutamate release from rat neocortex and hippocampal slices by gabapentin. Neurosci Lett 2001 Feb; 280(2): 107–10

    Article  Google Scholar 

  23. Dooley DJ, Donovan CM, Meder WP, et al. Preferential action of gabapentin and pregabalin at P/Q-type voltage-sensitive calcium channels: inhibition of K+-evoked. Synapse 2002 Sep 1; 45(3): 171–90

    Article  PubMed  CAS  Google Scholar 

  24. Taylor CP. Meeting report: the biology and pharmacology of calcium channel alpha2-delta proteins. Pfizer satellite symposium to the 2003 Society for Neuroscience Meeting. CNS Drug Rev 2004; 10(2): 159–64

    Google Scholar 

  25. 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; 105: 133–44

    Article  PubMed  CAS  Google Scholar 

  26. Corrigan BW, Pool WF, Posvar EL, et al. Metabolic disposition of pregabalin in healthy volunteers [abstract no. PI-68]. Clin Pharmacol Ther 2001 Feb; 69: P18

    Google Scholar 

  27. Bockbrader HN, Hunt T, Strand J, et al. Pregabalin pharmacokinetics and safety in healthy volunteers: results from two phase 1 studies [abstract no. P06.051]. Neurology 2000 Apr 11; 54 Suppl. 3: 421

    Google Scholar 

  28. Busch JA, Strand JC, Posvar EL, et al. Pregabalin (CI-1008) single-dose pharmacokinetics and safety/tolerance in healthy subjects after oral administration of pregabalin solution or capsule doses [abstract no. 2.108]. Epilepsia 1998; 39 Suppl. 6: 58

    Google Scholar 

  29. Dworkin RH, Corbin AE, Young Jr JP, et al. Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2003 Apr 22; 60(8): 1274–83

    Article  PubMed  CAS  Google Scholar 

  30. Randinitis EJ, Posvar EL, Alvey CW, et al. Pharmacokinetics of pregabalin in subjects with various degrees of renal function. J Clin Pharmacol 2003 Mar; 43(3): 277–83

    Article  PubMed  CAS  Google Scholar 

  31. Bockbrader HN, Wesche D. Pharmacokinetic profile of pregabalin: results of a series of studies [abstract no. NR378]. 157th Annual Meeting of the American Psychiatric Association; 2004 May 1–6; New York, 140

  32. Sabatowski R, Galvez R, Cherry DA, et al. Pregabalin reduces pain and improves sleep and mood disturbances in patients with postherpetic neuralgia: results of a randomised, placebo-controlled clinical trial. Pain 2004; 109: 26–35

    Article  PubMed  CAS  Google Scholar 

  33. Van Seventer R, Bladin C, Hoggart B, et al. Pregabalin dosed twice a day (BID) efficaciously and safely treats neuropathic pain associated with postherpetic neuralgia [abstract no. 800]. J Pain 2004; 5 Suppl. 1: 58

    Article  Google Scholar 

  34. Van Seventer R, Bladin C, Hoggart B, et al. Pregabalin dosed BID is efficacious for improving sleep interference in patients suffering from postherpetic neuralgia: results of a large, randomized, placebo-controlled trial [abstract no. 806]. J Pain 2004; 5 Suppl. 1: 60

    Article  Google Scholar 

  35. van Seventer R, Feister H, Young Jr JP, et al. pregabalin dosed twice daily improves health-related quality of life in patients with postherpetic neuralgia [abstract no. P1371]. 8th Congress of the European Federation of Neurological Sciences; 2004 Sep 4; Paris

  36. Rowbotham M, Young J, Sharma U, et al. Pregabalin shows reduction in pain by day three of treatment. J Pain 2003 Mar; 4 Suppl. 1: 63

    Article  Google Scholar 

  37. Portenoy R, Sharma U, Young J, et al. Pregabalin sustains its efficacy as long-term maintenance therapy for neuropathic pain associated with diabetic neuropathy and postherpetic neuralgia [abstract no. 599-P]. Diabetes 2004 Jun; 53 Suppl. 2: 142

    Google Scholar 

  38. Farrar JT, Young Jr JP, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001 Nov; 94(2): 149–58

    Article  PubMed  CAS  Google Scholar 

  39. Data on file, Pfizer, 2004

  40. Pfizer Inc. Pfizer receives approval to market Lyrica for neuropathic pain and add-on epilepsy in Europe [online]. Available from URL: http://www.pfizer.com/are/news_releases/2004pr/mn_2004_0706.html [Accessed 2004 Sep 28]

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  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 1311, New Zealand

    James E. Frampton & Rachel H. Foster

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  1. James E. Frampton
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  2. Rachel H. Foster
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Correspondence to James E. Frampton.

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Frampton, J.E., Foster, R.H. Pregabalin. Drugs 65, 111–118 (2005). https://doi.org/10.2165/00003495-200565010-00011

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