Comparative study on pharmacokinetics of a series of anticholinergics, atropine, anisodamine, anisodine, scopolamine and tiotropium in rats

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• 作者：Fengjie Tian ; Cuiyun Li ; Xin Wang…
• 关键词：Pharmacokinetics ; Anticholinergics ; Atropine ; like drugs ; Tiotropium
• 刊名：European Journal of Drug Metabolism and Pharmacokinetics
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：40
• 期：3
• 页码：245-253
• 全文大小：811 KB
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• 作者单位：Fengjie Tian (1)
  Cuiyun Li (1)
  Xin Wang (1)
  Shuangxia Ren (1)
  Ning Li (1)
  Qi Liu (1)
  Sufeng Zhou (1)
  Yang Lu (2)
  Di Zhao (1)
  Xijing Chen (1)
  
  1. Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China
  2. Department of Membrane Transport and Biopharmaceutics, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan
  
• 刊物主题：Pharmacology/Toxicology; Pharmacy; Human Physiology; Pharmaceutical Sciences/Technology; Medical Biochemistry;
• 出版者：Springer Paris
• ISSN：2107-0180

文摘

The compound series of traditional anticholinergics [atropine (Atr), anisodamine (Ani), anisodine (AT3), and scopolamine (Sco)], naturally occurring belladonna alkaloid, have been approved for numerous therapeutic uses since 1970s. Tiotropium, a novel M receptor antagonist for the treatment of chronic obstructive pulmonary disease, was structurally modified based on atropine-like drugs. Clinical phenomena suggested that the changes of substituent group were related to the pharmacokinetic and pharmacodynamic characteristics of the agents. In an attempt to compare the pharmacokinetics of the series of anticholinergics and investigate the subsets motivating selective anticholinergic potencies, a sensitive LC–MS/MS method was established to analyze the differences of pharmacokinetic parameters. In this paper, we determined the pharmacokinetics of atropine, anisodamine, anisodine, scopolamine, and tiotropium after i.v. and i.g. single dose administration. After i.v. administration, the maximum drug plasma concentrations (C _max) of Atr, Ani, AT3, and Sco were 274.25 ± 53.66, 267.50 ± 33.16, 340.50 ± 44.52, and 483.75 ± 78.13 ng/mL. Tiotropium had a slightly higher area under the curve with a significant increase of C _max value. Because of their partial solubility, Atr, Ani, AT3, and Sco had different bioavailability in rats of 21.62, 10.78, 80.45 and 2.52 %, respectively. Following i.g. administration of tiotropium, the C _max value below 20 ng/mL revealed the very low oral absorption. The urinary excretion rates of Atr, Ani, AT3, Sco and tiotropium were 11.33, 54.86, 32.67, 8.69 and 73.91 %. This work provided relatively comprehensive preclinical data on the series of anticholinergics, which may be used to explain the clinical adverse effects and applications. Keywords Pharmacokinetics Anticholinergics Atropine-like drugs Tiotropium