González M A, Estes K S
P'Kinetics Inc., Pembroke Pines, Florida 33027-2219, USA.
Int J Clin Pharmacol Ther. 1998 May;36(5):292-300.
Specific H1 antihistamines have become the standard of treatment for relief of symptoms associated with seasonal allergic rhinitis. First-generation antihistamines are small lipophilic molecules that are associated with numerous adverse events largely because of their propensity to cross the blood-brain barrier and their cholinergic activity. Second-generation antihistamines, being more lipophobic, offer the advantages of a lack of CNS and cholinergic effects such as sedation and dry mouth, which are commonly seen in first-generation antihistamines. Their longer duration of action also enables a more patient-friendly dosing regimen which increases patient compliance. This paper reviews the pharmacokinetic properties of these second-generation agents and is intended to provide comparisons that help explain differences in dosing profiles and drug interactions for members of this class of drugs. With the announced withdrawal of terfenadine from the U.S. market in early 1997, 4 second-generation antihistamines are currently widely available: astemizole, loratadine, cetirizine, and fexofenadine. Terfenadine and astemizole both produce significant cardiac QT interval prolongation that may progress to a rare but fatal cardiac ventricular tachycardia known as torsades de pointes. While only terfenadine has been withdrawn due to its adverse effects profile, significant warnings were recently issued for astemizole. The pharmacokinetic profiles of loratadine and cetirizine are reflective of the advantages of these agents as non-cardiotoxic antihistamines. With respect to the newest agent fexofenadine, the major metabolite of terfenadine, published reports are minimal, but its pharmacokinetics differs from that of terfenadine.
特定的H1抗组胺药已成为缓解季节性变应性鼻炎相关症状的治疗标准。第一代抗组胺药是亲脂性小分子，与众多不良事件相关，主要是因为它们易于穿过血脑屏障以及具有胆碱能活性。第二代抗组胺药亲脂性较低，具有不产生中枢神经系统和胆碱能效应（如第一代抗组胺药常见的镇静和口干）的优点。它们较长的作用持续时间还使得给药方案对患者更友好，从而提高患者的依从性。本文综述了这些第二代药物的药代动力学特性，旨在进行比较，以帮助解释这类药物在给药方案和药物相互作用方面的差异。随着特非那定于1997年初从美国市场撤出，目前有4种第二代抗组胺药广泛可用：阿司咪唑、氯雷他定、西替利嗪和非索非那定。特非那定和阿司咪唑均会使心脏QT间期显著延长，可能进展为一种罕见但致命的室性心动过速，即尖端扭转型室性心动过速。虽然仅特非那定因其不良反应情况而被撤出，但最近已对阿司咪唑发出了重大警告。氯雷他定和西替利嗪的药代动力学特征反映了这些药物作为非心脏毒性抗组胺药的优势。关于最新的药物非索非那定（特非那定的主要代谢产物），已发表的报告很少，但其药代动力学与特非那定不同。
