Some pharmacokinetic aspects of the lipophilic terfenadine and zwitterionic fexofenadine in humans.
Some pharmacokinetic aspects of the lipophilic terfenadine and zwitterionic fexofenadine in humans.
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DOI：
10.2165/00126839-200708050-00004
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发表时间：
2007-01-01
期刊：
影响因子：
3
通讯作者：
Chen, Chen
中科院分区：
文献类型：
--
作者：
Chen, Chen
非索非那定是第二代组胺H1受体拮抗剂（抗组胺药）特非那定的活性代谢产物，没有QT间期延长的缺点。此外，与第一代抗组胺药不同，它与CNS不良反应很少相关。在化学上，非索非那定具有两性离子结构，使其成为用作口服药物的有趣分子。非西非那定在人体内的肝脏代谢可忽略不计，口服给药后主要以原形形式在粪便中回收。非索非那定在人体内的绝对口服生物利用度尚不清楚，因为缺乏该药物静脉给药的研究。其表观消除半衰期（t1/2）范围为3 - 17小时，高度依赖于研究设计，即采血时间。这种巨大的差异可能与由两性离子分子的缓慢吸收引起的“触发器”现象有关。本文综述了非索非那定和特非那定的吸收、消除和排泄相关文献。基于这些数据，估计了非索非那定在人体中的分布容积、t1/2和口服生物利用度。了解这种药物的这些药代动力学方面可能是非常有用的药物化学家利用非索非那定/特非那定作为一个例子，设计两性离子化合物，以对抗心脏毒性和其他问题有关的基本和亲脂性分子。
Fexofenadine, an active metabolite of the second-generation histamine H1 receptor antagonist (antihistamine) terfenadine, does not have the disadvantage of QT prolongation. In addition, unlike first-generation antihistamines, it is associated with few CNS adverse effects. Chemically, fexofenadine has a zwitterionic structure that makes it an interesting molecule for use as an oral drug. Fexo-fenadine has negligible hepatic metabolism in humans, and is recovered mainly in the faeces in an unchanged form after oral administration. The absolute oral bioavailability of fexofenadine in humans is not known because of a lack of studies of intravenous administration of this agent. Its apparent elimination half-life (t1/2) ranges from 3 to 17 hours and is highly dependent on study design, i.e. the length of blood sampling. This large discrepancy might be associated with a 'flip-flop' phenomenon caused by slow absorption of the zwitterionic molecule. This review summarises the available literature related to the absorption, elimination and excretion of fexofenadine and terfenadine. Based on these data, the volume of distribution, t1/2 and oral bioavailability of fexofenadine in humans are estimated. Understanding these pharmacokinetic aspects of this drug might be very useful for medicinal chemists utilising fexofenadine/terfenadine as an example for designing zwitterionic compounds to combat cardiotoxicity and other issues related to basic and lipophilic molecules.