Pregabalin in neuropathic pain: a more "pharmaceutically elegant" gabapentin?
OBJECTIVE
This article reviews the available information on pregabalin, a new anticonvulsant for peripheral neuropathic pain. Pregabalin was provisionally approved by the US Food and Drug Administration in December 2004 and was granted final approval after controlled substance scheduling (Schedule V) by the US Drug Enforcement Agency in August 2005.


METHODS
A MEDLINE search (1986-August 2005) was conducted to identify pertinent studies in the English language. The search terms included pregabalin, PD144723, CI-1008, gabapentin, and neuropathic pain. Additional references were obtained from the bibliographies of identified articles. All studies that evaluated any aspect of pregabalin in vitro or in vivo in animals or humans were included, with a focus on data relevant to older adults.


RESULTS
In preclinical studies, pregabalin, a structural congener of gabapentin, exhibited antinociceptive activity in animal models of neuropathic and inflammatory pain. Unlike gabapentin, pregabalin was well absorbed (> 90%), and its absorption was dose independent. Like gabapentin, pregabalin was predominantly excreted unchanged in the urine (> or = 98%). Dosed at 50 to 200 mg TID, pregabalin was superior to placebo in relieving pain and improving sleep and health-related quality of life in patients with diabetic peripheral neuropathy and postherpetic neuralgia (P < 0.001-P < 0.049). No active-controlled trials were available. The most problematic adverse events associated with pregabalin were dizziness and somnolence (21%-26%).


CONCLUSIONS
In the absence of active-controlled clinical trials and geriatric-specific efficacy/tolerability data, the place of pregabalin in the analgesic armamentarium for the elderly is unclear. Because pregabalin is a Schedule V controlled substance, its utility is not compromised by substantial limitation of access or the need for extra steps in prescribing. However, abuse potential is a consideration, and utilization should be carefully monitored, particularly in patients with a past or current history of substance abuse. The improved pharmacokinetic profile of pregabalin relative to gabapentin is manifested in linear and dose-independent absorption and a narrow therapeutic dosing range. However, pregabalin still requires multiple administrations per day, and daily doses > 150 mg/d require dose titration. The relatively high frequency of central nervous system adverse events, particularly dizziness and somnolence, is a concern in the elderly. Time and further experience should clarify the role of this agent.
Guay
David R P
DR
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis 55455, USA. guayx001@umn.edu
D000368:Aged; D000588:Amines / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D004347:Drug Interactions; D000077206:Gabapentin; D006801:Humans; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000588:Amines; D018712:Analgesics, Non-Narcotic; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin