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Pharmacokinetics, metabolite profiling, safety, and tolerability of inhalation aerosol of 101BHG-D01, a novel, long-acting and selective muscarinic receptor antagonist, in healthy Chinese subjects.
Gao, Huaye; Li, Jintong; Chen, Xiaoping; Sun, Zhanguo; Cui, Gang; Cheng, Minlu; Ding, Li.
Afiliación
  • Gao H; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China.
  • Li J; Drug Clinical Trial Research Center, China-Japan Friendship Hospital, Beijing, China.
  • Chen X; Beijing Shuobai Pharmaceutical Technology Co., Ltd., Beijing, China.
  • Sun Z; Beijing Shuobai Pharmaceutical Technology Co., Ltd., Beijing, China.
  • Cui G; Drug Clinical Trial Research Center, China-Japan Friendship Hospital, Beijing, China.
  • Cheng M; Nanjing Jiening Pharmaceutical Technology Co., Ltd., Nanjing, China.
  • Ding L; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China.
Front Pharmacol ; 13: 1064364, 2022.
Article en En | MEDLINE | ID: mdl-36588683
101BHG-D01 is a novel, long-acting, selective muscarinic receptor antagonist for the treatment of chronic obstructive pulmonary disease (COPD). A single-site, randomized, double-blind, placebo-controlled and dose-escalation study of 101BHG-D01 inhalation aerosol was conducted to evaluate its pharmacokinetics, metabolite profiling, safety and tolerability following the single inhaled doses ranged from 20 to 900 µg in healthy Chinese subjects. After inhalation, 101BHG-D01 was absorbed rapidly into plasma with the time to maximum concentration about 5 min, and eliminated slowly with the terminal phase half-life about 30 h. The cumulative excretion rates of 101BHG-D01 in feces and urine were about 30% and 2%, respectively, which showed the study drug was mainly excreted in feces. The maximum drug concentration and area under the plasma concentration-time curve increased with dose escalation in the range of 20-600 µg, but their values increased out of proportion to the whole studied doses. The main metabolic pathways were loss of phenyl group and hydroxylation. No metabolite that presented at greater than 10 percent of total drug-related exposure was observed. 101BHG-D01 was safe and well tolerated after administration. The study results indicate that 101BHG-D01 is a good candidate for the treatment of COPD and enable further clinical development in subsequent studies in patients. Clinical Trial Registration: http://www.chinadrugtrials.org.cn; Identifier: CTR20192058.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Clinical_trials Idioma: En Revista: Front Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Clinical_trials Idioma: En Revista: Front Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza