Matzke G R, Yeh J, Awni W M, Halstenson C E, Chung M
Drug Evaluation Unit, Hennepin County Medical Center, Minneapolis, Minnesota.
Ann Allergy. 1987 Dec;59(6 Pt 2):25-30.
The disposition of cetirizine, a new H1-receptor antagonist, was evaluated in 30 healthy adults of various ages and in 15 adults with various degrees of renal insufficiency. The purpose of the evaluation was to determine whether dosage schedules of cetirizine will require modification in the elderly or patients with renal insufficiency. We found that the elimination half-life of cetirizine was prolonged in patients with mild and moderate renal insufficiency, compared with age-matched individuals with normal renal function (19.0 +/- 3.3 and 20.9 +/- 4.4 hours, vs 7.4 +/- 3.0 hours, respectively). However, the mean apparent steady-state volume of distribution did not differ significantly between these subject groups (range 0.41 to 0.47 L/kg). Total body clearance and renal clearance of the drug were both significantly lower in the patients with renal insufficiency. In elderly subjects, the elimination half-life of cetirizine was significantly prolonged compared with younger adults, and apparent total body clearance was significantly reduced. Again, there was no significant difference in the volume of distribution between the groups. Linear regression showed good correlations between the disposition characteristics of cetirizine and age as well as creatinine clearance. However, we found no relationship between age and the ratio of apparent total body clearance of cetirizine to creatinine clearance. Thus the disposition of cetirizine is independent of age but dependent on renal function. The relationship between apparent total body clearance of cetirizine and creatinine clearance was significant only in patients with creatinine clearances greater than 40 mL/min. Progressive decrements in creatinine clearance were not associated with similar changes in the pharmacokinetic parameters of cetirizine.
在30名不同年龄段的健康成年人以及15名不同程度肾功能不全的成年人中，对新型H1受体拮抗剂西替利嗪的处置情况进行了评估。评估目的是确定西替利嗪的给药方案是否需要在老年人或肾功能不全患者中进行调整。我们发现，与年龄匹配的肾功能正常个体相比，轻度和中度肾功能不全患者中西替利嗪的消除半衰期延长（分别为19.0±3.3小时和20.9±4.4小时，而正常肾功能者为7.4±3.0小时）。然而，这些受试者组之间的平均表观稳态分布容积没有显著差异（范围为0.41至0.47L/kg）。肾功能不全患者中该药物的总体清除率和肾清除率均显著降低。在老年受试者中，西替利嗪的消除半衰期与年轻成年人相比显著延长，表观总体清除率显著降低。同样，各组之间的分布容积没有显著差异。线性回归显示西替利嗪的处置特征与年龄以及肌酐清除率之间具有良好的相关性。然而，我们发现年龄与西替利嗪表观总体清除率与肌酐清除率的比值之间没有关系。因此，西替利嗪的处置情况与年龄无关，但取决于肾功能。西替利嗪的表观总体清除率与肌酐清除率之间的关系仅在肌酐清除率大于40mL/min的患者中显著。肌酐清除率的逐渐降低与西替利嗪的药代动力学参数的类似变化无关。
