دورية أكاديمية

Disposition and metabolism of [14C]-levomilnacipran, a serotonin and norepinephrine reuptake inhibitor, in humans, monkeys, and rats

التفاصيل البيبلوغرافية
العنوان: Disposition and metabolism of [14C]-levomilnacipran, a serotonin and norepinephrine reuptake inhibitor, in humans, monkeys, and rats
المؤلفون: Brunner V, Maynadier B, Chen L, Roques L, Hude I, Séguier S, Barthe L, Hermann P
المصدر: Drug Design, Development and Therapy, Vol 2015, Iss default, Pp 3199-3215 (2015)
بيانات النشر: Dove Medical Press, 2015.
سنة النشر: 2015
المجموعة: LCC:Therapeutics. Pharmacology
مصطلحات موضوعية: Therapeutics. Pharmacology, RM1-950
الوصف: Valérie Brunner,1 Bernadette Maynadier,2 Laishun Chen,3 Louise Roques,2 Isabelle Hude,2 Sébastien Séguier,2 Laurence Barthe,1 Philippe Hermann11Pierre Fabre Médicament, Centre de R&D, Toulouse, 2Centre Experimental PreClinque, Campans, France; 3Forest Research Institute Inc., an affiliate of Actavis Inc., Jersey City, NJ, USAAbstract: Levomilnacipran is approved in the US for the treatment of major depressive disorder in adults. We characterized the metabolic profile of levomilnacipran in humans, monkeys, and rats after oral administration of [14C]-levomilnacipran. In vitro binding of levomilnacipran to human plasma proteins was also studied. Unchanged levomilnacipran was the major circulating compound after dosing in all species. Within 12 hours of dosing in humans, levomilnacipran accounted for 52.9% of total plasma radioactivity; the circulating metabolites N-desethyl levomilnacipran N-carbamoyl glucuronide, N-desethyl levomilnacipran, and levomilnacipran N-carbamoyl glucuronide accounted for 11.3%, 7.5%, and 5.6%, respectively. Similar results were seen in monkeys. N-Desethyl levomilnacipran and p-hydroxy levomilnacipran were the main circulating metabolites in rats. Mass balance results indicated that renal excretion was the major route of elimination with 58.4%, 35.5%, and 40.2% of total radioactivity being excreted as unchanged levomilnacipran in humans, monkeys, and rats, respectively. N-Desethyl levomilnacipran was detected in human, monkey, and rat urine (18.2%, 12.4%, and 7.9% of administered dose, respectively). Human and monkey urine contained measurable quantities of levomilnacipran glucuronide (3.8% and 4.1% of administered dose, respectively) and N-desethyl levomilnacipran glucuronide (3.2% and 2.3% of administered dose, respectively); these metabolites were not detected in rat urine. The metabolites p-hydroxy levomilnacipran and p-hydroxy levomilnacipran glucuronide were detected in human urine (≤1.2% of administered dose), and p-hydroxy levomilnacipran glucuronide was found in rat urine (4% of administered dose). None of the metabolites were pharmacologically active. Levomilnacipran was widely distributed with low plasma protein binding (22%).Keywords: FETZIMA, metabolites, mass balance, excretion, tissue distribution
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1177-8881
Relation: http://www.dovepress.com/disposition-and-metabolism-of-14c-levomilnacipran-a-serotonin-and-nore-peer-reviewed-article-DDDT; https://doaj.org/toc/1177-8881
URL الوصول: https://doaj.org/article/37511a4cb2294b97a0a5fed9f9830309
رقم الأكسشن: edsdoj.37511a4cb2294b97a0a5fed9f9830309
قاعدة البيانات: Directory of Open Access Journals