Bioequivalence Study of Oral Suspension and Intravenous Formulation of Edaravone in Healthy Adult Subjects
العنوان: | Bioequivalence Study of Oral Suspension and Intravenous Formulation of Edaravone in Healthy Adult Subjects |
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المؤلفون: | Kazuoki Kondo, Yoshinobu Nakamaru, Manabu Hirai, Yukiko Nishimura, Kaori Yoshida, Munetomo Matsuda, Yuichiro Kato, Hidetoshi Shimizu, Youichi Shiide |
المصدر: | Clinical Pharmacology in Drug Development |
بيانات النشر: | Wiley, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | Adult, Male, amyotrophic lateral sclerosis, Adolescent, oral formulation, Drug Compounding, Urinary system, Cmax, Administration, Oral, Pharmaceutical Science, Original Manuscript, Pharmacology, Bioequivalence, 030226 pharmacology & pharmacy, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Sulfate conjugate, Suspensions, Oral administration, Edaravone, Humans, Medicine, Pharmacology (medical), Infusions, Intravenous, Cross-Over Studies, edaravone, biology, business.industry, Free Radical Scavengers, Articles, bioequivalence study, Crossover study, Healthy Volunteers, Therapeutic Equivalency, chemistry, 030220 oncology & carcinogenesis, biology.protein, Female, clinical pharmacology, ALS, Glucuronide, business |
الوصف: | The neuroprotective agent edaravone is an intravenous treatment for amyotrophic lateral sclerosis. As intravenous administration burdens patients, orally administered treatments are needed. This phase 1, open‐label, single‐dose crossover study in 42 healthy adults evaluated bioequivalence of a 105‐mg edaravone oral suspension and intravenous edaravone (60 mg/60 min). The evaluation was whether the 90% confidence intervals (CIs) for the ratio of the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from time 0 to the last quantifiable time point and to infinity of unchanged edaravone were between the bioequivalence limit of 0.80 and 1.25. Metabolic profiles and elimination pathways were also compared between the 2 routes. Geometric mean ratios and 90%CIs of area under the plasma concentration–time curve from time 0 to the last quantifiable time point and to infinity for unchanged edaravone satisfied bioequivalence limits. The geometric mean ratio and its lower limit of 90%CI of Cmax of the 105‐mg oral suspension compared with 60‐mg intravenous formulations for unchanged edaravone fell within bioequivalence limits. Both formulations showed triphasic plasma concentration–time profiles of unchanged edaravone after reaching Cmax. Plasma concentrations of edaravone inactive metabolites after oral administration were higher than with intravenous administration. Edaravone in both routes underwent urinary excretion, mainly as the glucuronide conjugate and, to a lesser extent, as the sulfate conjugate. Urinary excretion of unchanged edaravone was low, and urinary relative composition ratios of unchanged edaravone and metabolites were similar for both formulations. These findings showed equivalent exposure of the 105‐mg oral suspension of edaravone to the 60‐mg intravenous formulation, supporting further investigation of the oral suspension for treating amyotrophic lateral sclerosis. |
تدمد: | 2160-7648 2160-763X |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::952e26264326cd5a4a3a0e7867925efeTest https://doi.org/10.1002/cpdd.952Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....952e26264326cd5a4a3a0e7867925efe |
قاعدة البيانات: | OpenAIRE |
تدمد: | 21607648 2160763X |
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