Desager J P, Horsmans Y
Laboratoire de Pharmacotherapie, Universite Catholique de Louvain, Brussels, Belgium.
Clin Pharmacokinet. 1995 May;28(5):419-32. doi: 10.2165/00003088-199528050-00006.
Histamine H1-receptor antagonists are reversible, competitive inhibitors of the actions of histamine, a critical mediator in the pathophysiology of the allergic response. This review is mainly devoted to second generation antihistamines that possess a low sedation potential compared with first generation compounds. The pharmacokinetic and pharmacodynamic data of 10 compounds have been updated. Some values are lacking for drugs under development, but also for older antihistamines. Thereafter, pharmacokinetic-pharmacodynamic relationships are reported from published or original documents. A linear pharmacokinetic-pharmacodynamic relationship has been found for acrivastine, astemizole, cetirizine, ebastine and terfenadine, whereas nonlinear relationships have been calculated for ebastine (in the dog), levocabastine, mizolastine, noberastine and terfenadine. It must be concluded that this type of approach for therapeutic optimisation is very fruitful and may enable large numbers of clinical studies to be avoided. Trends for the future include: (i) in vitro binding studies with the human H1-receptor obtained by molecular biology; (ii) the characterisation of the cytochromes P450 responsible for the biotransformation of antihistamine; (iii) the calculation of the pharmacokinetic-pharmacodynamic relationship in healthy individuals; and (iv) prospective effect-controlled clinical studies.
组胺H1受体拮抗剂是组胺作用的可逆性竞争性抑制剂，组胺是过敏反应病理生理学中的关键介质。本综述主要关注与第一代化合物相比具有低镇静潜力的第二代抗组胺药。已更新了10种化合物的药代动力学和药效学数据。一些正在研发的药物以及较老的抗组胺药缺乏相关数据。此后，从已发表或原始文献中报告了药代动力学-药效学关系。已发现阿伐斯汀、阿司咪唑、西替利嗪、依巴斯汀和特非那定存在线性药代动力学-药效学关系，而依巴斯汀（在犬中）、左卡巴斯汀、咪唑斯汀、诺贝斯汀和特非那定则计算出非线性关系。必须得出结论，这种治疗优化方法非常有效，可能避免大量临床研究。未来的趋势包括：（i）利用分子生物学获得的人H1受体进行体外结合研究；（ii）鉴定负责抗组胺药生物转化的细胞色素P450；（iii）计算健康个体中的药代动力学-药效学关系；（iv）前瞻性效应对照临床研究。
