Simons F E, Watson W T, Minuk G Y, Simons K J
Health Sciences Clinical Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
J Clin Pharmacol. 1993 Oct;33(10):949-54. doi: 10.1002/j.1552-4604.1993.tb01928.x.
The new H1-receptor antagonist, cetirizine, is eliminated primarily unchanged by renal excretion and is thus potentially useful for relief of pruritus in patients with hepatic dysfunction, in whom many H1-receptor antagonists are contraindicated. The authors studied the elimination of cetirizine in six patients with primary biliary cirrhosis. In contrast to data obtained in healthy adults with normal hepatic function reported in the medical literature, they found that the mean serum elimination half-life value of cetirizine, 13.8 +/- 1.8 hours, was longer, and the mean clearance rate, 0.44 +/- 0.10 mL/min/kg, was lower (P < .05). The mean peak serum cetirizine concentration, 498 +/- 118 ng/mL, was higher, the mean area under the curve, 6438 +/- 1621 ng/mL/hr, was larger, and the mean fraction of the dose excreted as unchanged cetirizine in the urine, .32 +/- .14, was lower (P < .05). The duration of action of cetirizine was prolonged, as evidenced by significant suppression of the histamine-induced wheal and flare for 48 and 72 hours, respectively, after a single dose. Cetirizine elimination was impaired in patients with hepatic dysfunction.
新型H1受体拮抗剂西替利嗪主要通过肾脏排泄以原形消除，因此对于肝功能不全患者的瘙痒缓解可能有用，而许多H1受体拮抗剂在这类患者中是禁忌的。作者研究了6例原发性胆汁性肝硬化患者中西替利嗪的消除情况。与医学文献中报道的肝功能正常的健康成年人的数据相比，他们发现西替利嗪的平均血清消除半衰期值（13.8±1.8小时）更长，平均清除率（0.44±0.10 mL/min/kg）更低（P<0.05）。西替利嗪的平均血清峰值浓度（498±118 ng/mL）更高，平均曲线下面积（6438±1621 ng/mL/hr）更大，以原形西替利嗪形式经尿液排泄的剂量平均分数（0.32±0.14）更低（P<0.05）。单次给药后，西替利嗪的作用持续时间延长，表现为组胺诱导的风团和潮红分别被显著抑制48小时和72小时。肝功能不全患者的西替利嗪消除受损。
