Affiliation:
1. Innovative Medicines R&D Global Clinical Development Teva Pharmaceuticals West Chester PA USA
2. Innovative Medicines R&D Global Clinical Development Teva Pharmaceuticals Netanya Israel
3. Watson Pharma Pvt. Ltd. Seawoods Navi‐Mumbai Maharashtra India
4. Teva Clinics Miramar FL USA
Abstract
AbstractDeutetrabenazine is approved for the treatment of tardive dyskinesia and chorea associated with Huntington's disease. This study compared the exposure between the once‐daily (test) and twice‐daily (reference) formulations of deutetrabenazine under fed conditions. Using a randomized crossover design, healthy adults (n = 262) received the 24 mg of the test formulation once daily and 12 mg of the reference formulation twice daily, each for 7 days. Plasma concentrations were collected on Days 4‐6 before dose intake, and frequently for pharmacokinetic evaluation on Days 6 and 7 for determination of deutetrabenazine and active metabolites, deuterated α‐dihydrotetrabenazine (α‐HTBZ) and β‐dihydrotetrabenazine (β‐HTBZ). Geometric mean ratios (GMRs, test/reference) were computed for all analytes, and bioequivalence was tested for area under the plasma concentration‐time curve over 24 hours at steady state (AUC0‐24 h,ss) and for maximum plasma concentrations at steady state (Cmax,ss). The GMRs for AUC0‐24 h,ss were 115% for deutetrabenazine and 95% for deuterated total (α+β)‐HTBZ; and the GMR for Cmax,ss for deutetrabenazine was 95%. Relative bioavailability was assessed for Cmax,ss of the active metabolites; the GMR was 78% for total (α+β)‐HTBZ. At steady state, deutetrabenazine administered as the once‐daily formulation was bioequivalent to the twice‐daily formulation for both AUC and Cmax, and the active metabolites were bioequivalent with regard to AUC0‐24 h,ss.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献