Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro / R. Scott Obach (2006)

Public Titre : Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro Type de document : texte imprimé Auteurs : R. Scott Obach, Auteur ; Anne E. Reed-Hagen, Auteur ; Suzanne S. Krueger, Auteur ; Beth J. Obach, Auteur Editeur : American Society for Pharmacology and Experimental Therapeutic Année de publication : 2006 Collection : Drug Metabolism and Disposition, ISSN 0090-9556 num. 34:1 Importance : p. 121-130 Présentation : tab., graph. Langues : Anglais (eng) Catégories : [TABAC] étude [TABAC] sevrage tabagique:méthode de sevrage:méthode individuelle:approche pharmacologique:varénicline Index. décimale : TA 6.2.3.2 Autres produits Résumé : he metabolism and disposition of varenicline (7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine), a partial agonist of the nicotinic acetylcholine receptor for the treatment of tobacco addiction, was examined in rats, mice, monkeys, and humans after oral administration of [14C]varenicline. In the circulation of all species, the majority of drug-related material was composed of unchanged varenicline. In all four species, drug-related material was primarily excreted in the urine. A large percentage was excreted as unchanged parent drug (90, 84, 75, and 81% of the dose in mouse, rat, monkey, and human, respectively). Metabolites observed in excreta arose via N-carbamoyl glucuronidation and oxidation. These metabolites were also observed in the circulation, in addition to metabolites that arose via N-formylation and formation of a novel hexose conjugate. Experiments were conducted using in vitro systems to gain an understanding of the enzymes involved in the formation of the N-carbamoylglucuronide metabolite in humans. N-Carbamoyl glucuronidation was catalyzed by UGT2B7 in human liver microsomes when incubations were conducted under a CO2 atmosphere. The straightforward dispositional profile of varenicline should simplify its use in the clinic as an aid in smoking cessation. Permalink : https://biblio.fares.be/opac_css/index.php?lvl=notice_display&id=8368

Exemplaires (1)

Code-barres	Cote	Support	Localisation	Section	Disponibilité
TA 005999	TA 6.2.3.2 OBA M	Article/Périodique	Bibliothèque FARES	Tabac	Consultation sur place Exclu du prêt

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Varenicline / Victor I. Reus (2007)  

Public Titre : Varenicline : new treatment with efficacy in smoking cessation Type de document : texte imprimé Auteurs : Victor I. Reus, Auteur ; R. Scott Obach, Auteur ; Jotham W. Coe, Auteur ; Helene Faessel, Auteur ; Hans Rollema, Auteur ; Eric Watsky, Auteur ; Karen Reeves, Auteur Editeur : Barcelona [Espagne] : Thomson Reuters Année de publication : 2007 Collection : Drugs of today, ISSN 1699-3993 num. 43(2) Importance : p.65-75 Langues : Anglais (eng) Catégories : [TABAC] sevrage tabagique [TABAC] sevrage tabagique:efficacité du sevrage [TABAC] sevrage tabagique:méthode de sevrage:méthode individuelle:approche pharmacologique:varénicline Index. décimale : TA 6.2.3.1.4 Autres substituts nicotiniques Résumé : Smoking is a significant public health problem, and existing treatments have demonstrated only moderate efficacy in assisting smokers to quit. Varenicline, recently approved by the U.S. Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products as an aid to smoking cessation treatment, has a novel mechanism of action, targeting the specific nicotinic acetylcholine receptor (nAChR) associated with nicotine-induced behaviors (alpha4beta2 nAChR). It has both agonistic and antagonistic properties that together are believed to account for reduction of craving and withdrawal as well as blocking the rewarding effects of smoking. The clinical efficacy and tolerability of varenicline has been demonstrated in phase III clinical trials involving more than 2,000 cigarette smokers. At the end of the treatment period in two 12-week, multicenter, randomized, double-blind, placebo-controlled studies, patients receiving varenicline (1 mg twice daily) experienced an increase in the odds of quitting smoking by nearly fourfold compared with those receiving placebo, and almost twofold compared with the odds for patients receiving 150 mg bupropion SR (sustained release) twice daily. In these two trials where patients were randomized to either varenicline or bupropion, the efficacy of varenicline was consistently superior at 12 weeks; this result sustained significance at 24 weeks in both studies and up to 52 weeks in one study. Nausea, a common adverse event reported in clinical trials, led to few treatment discontinuations. Its targeted mechanism of action, superior efficacy and excellent tolerability make varenicline a welcome and useful addition to the therapeutic options for smoking cessation. En ligne : https://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_ [...] Format de la ressource électronique : PDF, HTML Permalink : https://biblio.fares.be/opac_css/index.php?lvl=notice_display&id=7932

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