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. |
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