The Bioequivalence of Tafamidis 61‐mg Free Acid Capsules and Tafamidis Meglumine 4 × 20‐mg Capsules in Healthy Volunteers

Autor:	Ekaterina Tankisheva, Melissa O'Gorman, Marla B. Sultan, Vu Le, Steve Riley, Terrell A. Patterson, Qiang Wang, Peter Lockwood
Rok vydání:	2020
Předmět:	Male Tafamidis Administration Oral Pharmaceutical Science Pharmacology Amyloid Neuropathies 030226 pharmacology & pharmacy chemistry.chemical_compound 0302 clinical medicine Japan Prealbumin Medicine Pharmacology (medical) media_common Benzoxazoles education.field_of_study Cross-Over Studies biology Articles Fasting Middle Aged Healthy Volunteers Tolerability 030220 oncology & carcinogenesis Disease Progression Female Safety Cardiomyopathies pharmacokinetics Brazil Adult Canada Drug Compounding Population Original Manuscript Bioequivalence transthyretin Drug Administration Schedule 03 medical and health sciences Pharmacokinetics Humans media_common.cataloged_instance tafamidis European union education amyloidosis bioequivalence Amyloid Neuropathies Familial Dose-Response Relationship Drug business.industry Tafamidis Meglumine United States Transthyretin Therapeutic Equivalency chemistry biology.protein business
Zdroj:	Clinical Pharmacology in Drug Development
ISSN:	2160-7648 2160-763X
DOI:	10.1002/cpdd.789
Popis:	Tafamidis, a non‐nonsteroidal anti‐inflammatory benzoxazole derivative, acts as a transthyretin (TTR) stabilizer to slow progression of TTR amyloidosis (ATTR). Tafamidis meglumine, available as 20‐mg capsules, is approved in more than 40 countries worldwide for the treatment of adults with early‐stage symptomatic ATTR polyneuropathy. This agent, administered as an 80‐mg, once‐daily dose (4 × 20‐mg capsules), is approved in the United States, Japan, Canada, and Brazil for the treatment of hereditary and wild‐type ATTR cardiomyopathy in adults. An alternative single solid oral dosage formulation (tafamidis 61‐mg free acid capsules) was developed and introduced for patient convenience (approved in the United States, United Arab Emirates, and European Union). In this single‐center, open‐label, randomized, 2‐period, 2‐sequence, crossover, multiple‐dose phase 1 study, the rate and extent of absorption were compared between tafamidis 61‐mg free acid capsules (test) and tafamidis meglumine 80‐mg (4 × 20‐mg) capsules (reference) after 7 days of repeated oral dosing under fasted conditions in 30 healthy volunteers. Ratios of adjusted geometric means (90%CI) for the test/reference formulations were 102.3 (98.0‐106.8) for area under the concentration‐time profile over the dosing interval and 94.1 (89.1‐99.4) for the maximum observed concentration, satisfying prespecified bioequivalence acceptance criteria (90%CI, 80‐125). Both tafamidis regimens had an acceptable safety/tolerability profile in this population.
Databáze:	OpenAIRE
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