Eva-Maria Sunzel, Laura Rabinovich-Guilatt, Malini Iyengar, Debra Ruffo, Nagnath G. Birajdar, Pippa Loupe, Maria Gutierrez, Mark Forrest Gordon, Giulia Ghibellini
{"title":"每日一次缓释片剂和每日两次片剂在稳定状态下的生物等效性比较","authors":"Eva-Maria Sunzel, Laura Rabinovich-Guilatt, Malini Iyengar, Debra Ruffo, Nagnath G. Birajdar, Pippa Loupe, Maria Gutierrez, Mark Forrest Gordon, Giulia Ghibellini","doi":"10.1002/cpdd.1355","DOIUrl":null,"url":null,"abstract":"<p>Deutetrabenazine 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 (AUC<sub>0-24 h,ss</sub>) and for maximum plasma concentrations at steady state (C<sub>max,ss</sub>). The GMRs for AUC<sub>0-24 h,ss</sub> were 115% for deutetrabenazine and 95% for deuterated total (α+β)-HTBZ; and the GMR for C<sub>max,ss</sub> for deutetrabenazine was 95%. Relative bioavailability was assessed for C<sub>max,ss</sub> 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 C<sub>max,</sub> and the active metabolites were bioequivalent with regard to AUC<sub>0-24 h,ss</sub>.</p>","PeriodicalId":10495,"journal":{"name":"Clinical Pharmacology in Drug Development","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cpdd.1355","citationCount":"0","resultStr":"{\"title\":\"A Bioequivalence Comparison Between the Once-Daily Extended-Release Tablet and the Twice-Daily Tablet Formulations of Deutetrabenazine at Steady State\",\"authors\":\"Eva-Maria Sunzel, Laura Rabinovich-Guilatt, Malini Iyengar, Debra Ruffo, Nagnath G. Birajdar, Pippa Loupe, Maria Gutierrez, Mark Forrest Gordon, Giulia Ghibellini\",\"doi\":\"10.1002/cpdd.1355\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Deutetrabenazine 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 (AUC<sub>0-24 h,ss</sub>) and for maximum plasma concentrations at steady state (C<sub>max,ss</sub>). The GMRs for AUC<sub>0-24 h,ss</sub> were 115% for deutetrabenazine and 95% for deuterated total (α+β)-HTBZ; and the GMR for C<sub>max,ss</sub> for deutetrabenazine was 95%. Relative bioavailability was assessed for C<sub>max,ss</sub> of the active metabolites; the GMR was 78% for total (α+β)-HTBZ. 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A Bioequivalence Comparison Between the Once-Daily Extended-Release Tablet and the Twice-Daily Tablet Formulations of Deutetrabenazine at Steady State
Deutetrabenazine 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.
期刊介绍:
Clinical Pharmacology in Drug Development is an international, peer-reviewed, online publication focused on publishing high-quality clinical pharmacology studies in drug development which are primarily (but not exclusively) performed in early development phases in healthy subjects.