Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0600142 (hot flushes)
 1,242 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Depomed is developing an extended-release (ER) oral formulation of gabapentin, a GABA receptor agonist commonly used for the treatment of epilepsy and seizures, neuropathic pain and hot flushes. Gabapentin ER is based on the company's proprietary AcuForm drug delivery technology, which is part of the Gastric Retention (GR) family of technologies; this offers improved drug absorption and bioavailability compared with the existing immediate-release formulation of gabapentin (Neurontin), making gabapentin ER suitable for twice-daily dosing. The product is in clinical development for the treatment of postherpetic neuralgia and diabetic neuropathies in the US. Additionally, Depomed has commenced a phase II trial of gabapentin ER in postmenopausal patients with hot flushes. Depomed's AcuForm platform is based on polymer technology that provides targeted drug delivery for a variety of compounds. Following ingestion, AcuForm tablets swell and are retained for 6-8 hours in the stomach, enabling controlled and prolonged release of gabapentin to the upper intestinal tract; this extends the time of drug delivery to the small intestine for complete and safe elimination via the lower intestinal track. Gabapentin ER is available for licensing. Depomed acquired exclusive development and commercialisation rights to gabapentin ER in September 2003 via its subsidiary, Depomed Development Ltd (DDL). Depomed is not required to pay upfront license fees, but will make royalty and milestone payments to DDL upon successful commercialisation of gabapentin ER. Gabapentin ER was originally developed by DDL, a joint venture between Depomed and Elan established in January 2000 to design products using the GR family of technologies. However, in efforts to restructure joint venture relationships, Elan withdrew from operational involvement of DDL in September 2003, and Depomed has gained full ownership of DDL. Depomed sublicensed exclusive rights to a US patent (held by the University of Rochester) covering the use of gabapentin in the treatment of hot flushes from PharmaNova in October 2006. Under the agreement, Depomed paid PharmaNova an upfront fee of US dollars 500 000. PharmaNova is also entitled to milestone payments and royalties on sales of gabapentin ER in this indication only. Depomed has reported significant safety and efficacy benefits from gabapentin ER in its phase II trial. This study was initiated in February 2005 following positive results from a phase I trial in which gabapentin ER demonstrated a pharmacokinetic profile suitable for twice-daily dosing. In two pharmacokinetic studies, gabapentin ER achieved improved bioavailability at higher doses. This result supports Depomed's development of a once- or twice-daily product with potentially fewer adverse events. The basic US patents relating to gabapentin expired in 2000. Depomed holds exclusive rights to a US patent (No. 6 310 098) held by the University of Rochester covering the use of gabapentin to treat hot flushes.Additionally, Depomed was issued a US patent (No. 6 723 340) in May 2004 that covers proprietary polymer combinations (as used in AcuForm tablets) to create improved formulations of existing drugs.
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PMID:Gabapentin Extended-Release - Depomed: Gabapentin ER, Gabapentin Gastric Retention, Gabapentin GR. 1776 96

Hot flashes occur frequently in menopausal women and in women with breast cancer, diminishing their quality of life. A report from the Women's Health Initiative published in 2002 raised concerns about the long-term safety of estrogen therapy. As a result, nonhormonal alternatives have emerged as preferred treatments. Gabapentin is an anticonvulsant that the United States Food and Drug Administration approved as an adjunct therapy for partial seizures and postherpetic neuralgia. Somnolence, dizziness, ataxia, fatigue, nystagmus, and peripheral edema are adverse effects commonly associated with gabapentin in the treatment of epilepsy and postherpetic neuralgia. The North American Menopause Society and the American College of Obstetricians and Gynecologists recommend the use of gabapentin as an option for managing hot flashes in women who are unwilling to take estrogen-containing supplements. To evaluate the efficacy and safety of gabapentin for the treatment of hot flashes in women with menopause and/or breast cancer, we performed a search of the MEDLINE database (1966-March 2008) and International Pharmaceutical Abstracts, as well as manually searching reference articles for relevant articles and abstracts; 10 clinical studies were identified. Although the studies were few, all showed gabapentin to be safe and effective in the treatment of hot flashes. At doses used to control hot flashes, gabapentin was well tolerated, with drowsiness as its most reported adverse effect. Gabapentin can be considered effective in the treatment of hot flashes and should be considered a reasonable alternative when estrogen therapy is not desired.
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PMID:Use of gabapentin in patients experiencing hot flashes. 1911 98

Gabapentin (GP) and pregabalin (PB) are structurally related compounds and their predominant mechanism of action is the inhibition of calcium currents via high-voltage-activated channels containing the a2d-1 subunit. A2delta ligands are approved for the treatment of pain of diabetic neuropathy and post-herpetic neuralgia in adults and as adjunctive therapy of partial seizures in children. Recently, pregabalin has been approved for treatment of anxiety disorders in Europe. Besides their already approved indications both drugs are promising treatment options for a number of different serious and debilitating diseases, as fibromyalgia, neuropathic pain of spinal cord injury, hot flushes, and essential tremor. In the present review, the unique mechanism of action of the above drugs is critically analyzed and evidence for their future use is provided. Gabapentin and pregabalin can be treatment options for these disorders, however, a clear comparison between the two drugs can not be performed, since there is no direct comparison study. The most common side effects are dizziness and somnolence which are also the most frequent reasons for withdrawal. Recommendations for future studies should include assessment of ideal titration period for GP and PB to reduce incidence of somnolence and dizziness and increase tolerability, cost-effectiveness and dose-response analysis of PB and GP and direct comparison of the two drugs.
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PMID:A2delta ligands gabapentin and pregabalin: future implications in daily clinical practice. 2059 59