Pharmacokinetic and Metabolic Profile of Deutetrabenazine (TEV-50717) Compared With Tetrabenazine in Healthy Volunteers.


Journal

Clinical and translational science
ISSN: 1752-8062
Titre abrégé: Clin Transl Sci
Pays: United States
ID NLM: 101474067

Informations de publication

Date de publication:
07 2020
Historique:
received: 04 10 2019
revised: 26 11 2019
accepted: 23 12 2019
pubmed: 11 3 2020
medline: 3 9 2021
entrez: 11 3 2020
Statut: ppublish

Résumé

Deutetrabenazine (Austedo, Teva Pharmaceuticals) is a deuterated form of tetrabenazine. It is the first deuterated drug to receive US regulatory approval and is approved for treatment of chorea in Huntington's disease and tardive dyskinesia. Two oral single dose studies comparing deutetrabenazine (25 mg) with tetrabenazine (25 mg) in healthy volunteers evaluated the impact of deuteration on pharmacokinetics of the active metabolites, alpha-dihydrotetrabenazine (α-HTBZ) and beta-dihydrotetrabenazine (β-HTBZ), metabolite profile, safety, and tolerability. In the two-way, cross-over study, the mean elimination half-life of deuterated total (α + β)-HTBZ was doubled compared with nondeuterated total (α + β)-HTBZ, with a twofold increase in overall mean exposure (area under the concentration-time curve from zero to infinity (AUC

Identifiants

pubmed: 32155315
doi: 10.1111/cts.12754
pmc: PMC7359938
doi:

Substances chimiques

Adrenergic Uptake Inhibitors 0
deutetrabenazine P341G6W9NB
Tetrabenazine Z9O08YRN8O

Types de publication

Comparative Study Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

707-717

Informations de copyright

© 2020 Ratiopharm GmbH/Teva Pharmaceutical Industries Ltd. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.

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Auteurs

Frank Schneider (F)

Teva Pharmaceutical Industries, Ratiopharm GmbH, Ulm, Germany.

Margaret Bradbury (M)

Formerly of Teva Pharmaceuticals, Alterity Therapeutics Limited, Newark, California, USA.

Thomas A Baillie (TA)

Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, Washington, USA.

David Stamler (D)

Formerly of Teva Pharmaceuticals, Alterity Therapeutics Limited, Newark, California, USA.

Edward Hellriegel (E)

Teva Pharmaceutical Products R&D, Inc., West Chester, Pennsylvania, USA.

Donna S Cox (DS)

Formerly of Teva Pharmaceuticals, Pfizer Corporation, Norristown, Pennsylvania, USA.

Pippa S Loupe (PS)

Teva Pharmaceuticals Industries, New Orleans, Louisiana, USA.

Juha-Matti Savola (JM)

Teva Pharmaceuticals International GmbH, Basel, Switzerland.

Laura Rabinovich-Guilatt (L)

Teva Pharmaceutical Industries, Netanya, Israel.

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Classifications MeSH