Mass balance and metabolism of aclidinium bromide following intravenous administration of [14C]-aclidinium bromide in healthy subjects

被引:10
|
作者
Ortiz, Stephan [1 ]
Flach, Stephen [2 ]
Ho, John
Li, Fanying
Caracta, Cynthia F.
Garcia Gil, Esther [3 ]
Jansat, Josep M. [3 ]
机构
[1] Forest Res Inst Inc, Harborside Financial Ctr, Jersey City, NJ 07311 USA
[2] Covance Clin Res Unit Inc, Madison, WI USA
[3] Almirall SA, Barcelona, Spain
关键词
aclidinium bromide; COPD; mass balance; pharmacokinetics; metabolism; MUSCARINIC ANTAGONIST; PHARMACOKINETICS; SAFETY;
D O I
10.1002/bdd.1773
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aclidinium bromide is a novel, inhaled long-acting muscarinic antagonist with low systemic activity developed for the treatment of COPD. It is an ester compound rapidly hydrolysed in plasma into inactive alcohol and acid metabolites. In this Phase I, open-label study, the rates and routes of elimination of radioactivity following intravenous administration of [14C]-aclidinium bromide were determined. The metabolites of aclidinium were also characterized and identified in plasma and excreta. Twelve healthy males were randomized (1:1) to receive a single intravenous 400 mu g dose of [phenyl-U-14C]- or [glycolyl-U-14C]-aclidinium bromide (via 5?min infusion) to label alcohol or acid metabolites of aclidinium, respectively. Safety and tolerability were assessed over a 9-day period. Following intravenous administration, the parent compound was rapidly hydrolysed into its acid and alcohol metabolites. Primary excretion routes for [phenyl-U-14C]- and [glycolyl-U-14C]-aclidinium were renal (urine: 65% and 54%, respectively; feces: 33% and 20%, respectively), with 1% excreted as unchanged aclidinium. A total of three treatment-emergent adverse events in two subjects were reported and were related to infusion site pain. Overall, aclidinium is rapidly hydrolysed into two main metabolites, which are predominantly excreted in urine. Aclidinium bromide 400 mu g administered intravenously was safe and well tolerated in healthy subjects. Copyright (C) 2012 John Wiley & Sons, Ltd.
引用
收藏
页码:39 / 45
页数:7
相关论文
共 50 条
  • [31] Mass balance, metabolic disposition, and pharmacokinetics of [14C]ensartinib, a novel potent anaplastic lymphoma kinase (ALK) inhibitor, in healthy subjects following oral administration
    Sufeng Zhou
    Wei Liu
    Chen Zhou
    Lingling Zhang
    Lijun Xie
    Zhaoqiang Xu
    Lu Wang
    Yuqing Zhao
    Lian Guo
    Juan Chen
    Lieming Ding
    Li Mao
    Yi Tao
    Chen Zhang
    Sijia Ding
    Feng Shao
    Cancer Chemotherapy and Pharmacology, 2020, 86 : 719 - 730
  • [32] A Phase I, Open-Label, Mass Balance Study of [14C]-Iberdomide in Healthy Subjects
    Yiming Cheng
    Xiaomin Wang
    Liangang Liu
    Jose Silva
    Michael Thomas
    Yan Li
    European Journal of Drug Metabolism and Pharmacokinetics, 2024, 49 : 355 - 365
  • [33] A Phase I, Open-Label, Mass Balance Study of [14C]-Iberdomide in Healthy Subjects
    Cheng, Yiming
    Wang, Xiaomin
    Liu, Liangang
    Silva, Jose
    Thomas, Michael
    Li, Yan
    EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, 2024, 49 (03) : 355 - 365
  • [34] Pharmacokinetics, mass balance, tissue distribution, metabolism, and excretion of [14C]aficamten following single oral dose administration to rats
    Grillo, Mark P.
    Sukhun, Rajaa
    Bashir, Mohammad
    Ashcraft, Luke
    Morgan, Bradley P.
    XENOBIOTICA, 2024, 54 (09) : 670 - 685
  • [35] Pharmacokinetics, excretion, and mass balance of 14C after administration of 14C-cholesterol-labeled AmBisome to healthy volunteers
    Bekersky, I
    Fielding, RM
    Dressler, DE
    Kline, S
    Buell, DN
    Walsh, TJ
    JOURNAL OF CLINICAL PHARMACOLOGY, 2001, 41 (09): : 963 - 971
  • [36] THE MASS BALANCE, RECOVERY, ABSORPTION, METABOLISM, AND EXCRETION OF [14C]-ORVEPITANT IN HEALTHY MALE SUBJECTS AFTER ORAL DOSING: METABOLITE CHARACTERISATION
    Colato, Dimitri
    Bordini, Ellenia
    Cufari, Domenico
    Lock, Ruth
    Pawsey, Steve
    Melbourne, Sue
    Shaw, Iain
    DRUG METABOLISM AND PHARMACOKINETICS, 2024, 55
  • [37] COMPARISON OF CEREBRAL REGIONAL METABOLISM OF [14C]LEUCINE FOLLOWING THIRD VENTRICLE AND INTRAVENOUS ADMINISTRATION IN CAT
    BERL, S
    FRIGYESI, TL
    JOURNAL OF NEUROCHEMISTRY, 1969, 16 (03) : 405 - +
  • [38] An open-label, single dose study designed to assess the metabolism and mass balance recovery for [14C]-eravacycline in healthy male subjects after oral and intravenous dosing
    Shaw, Iain
    Wood, Stuart
    Mair, Stuart
    Sutcliffe, Joyce A.
    Preskey, Clare
    DRUG METABOLISM REVIEWS, 2016, 48 : 59 - 59
  • [39] Pharmacokinetics, metabolism, and excretion of linezolid following an oral dose of [14C]linezolid to healthy human subjects
    Slatter, JG
    Stalker, DJ
    Feenstra, KL
    Welshman, IR
    Bruss, JB
    Sams, JP
    Johnson, MG
    Sanders, PE
    Hauer, MJ
    Fagerness, PE
    Stryd, RP
    Peng, GW
    Shobe, EM
    DRUG METABOLISM AND DISPOSITION, 2001, 29 (08) : 1136 - 1145
  • [40] Metabolism, Excretion, and Mass Balance of [14C]-Rezafungin in Animals and Humans
    Ong, Voon
    Wills, Sarah
    Watson, Deborah
    Sandison, Taylor
    Flanagan, Shawn
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2022, 66 (01)