Knauf H, Mutschler E
Eur J Clin Pharmacol. 1984;26(4):513-20. doi: 10.1007/BF00542150.
The effect of a single oral dose of 40 mg xipamide on urinary excretion of Na+, K+, Cl-, Ca2+ and Mg2+ in healthy subjects and in patients with varying degrees of renal impairment was compared with various conventional diuretics. Xipamide caused marked excretion of Na+ and Cl-, whereas the diuretic produced only moderate kaliuresis; urinary excretion of Ca2+ was increased in proportion to Na+, like the loop diuretics. Xipamide affected electrolyte excretion even in patients with a creatinine clearance below 30 ml/min, as do the loop diuretics, too. Therefore, the pharmacodynamic characteristics of xipamide are more like those of a loop diuretic than of a thiazide. Xipamide was good bioavailable, its t 1/2 beta was 7 h and urinary recovery of the undegraded drug was 40% of the given dose. In renal insufficiency, t 1/2 beta increased from 7 to only 9h, yielding a moderate increase in the AUC. Urinary recovery of the drug was reduced in proportion to the reduction in the creatinine clearance of the patient. Therefore, significant extrarenal elimination of the diuretic must be postulated, which suffices to prevent significant drug accumulation in renal failure.
将40毫克希帕胺单次口服给药对健康受试者以及不同程度肾功能损害患者尿中Na+、K+、Cl-、Ca2+和Mg2+排泄的影响，与各种传统利尿剂进行了比较。希帕胺可引起显著的Na+和Cl-排泄，而该利尿剂仅产生中度的尿钾增多；与袢利尿剂一样，Ca2+的尿排泄量随Na+成比例增加。即使在肌酐清除率低于30 ml/min的患者中，希帕胺也会影响电解质排泄，袢利尿剂也是如此。因此，希帕胺的药效学特征更类似于袢利尿剂而非噻嗪类利尿剂。希帕胺具有良好的生物利用度，其t 1/2β为7小时，未降解药物的尿回收率为给药剂量的40%。在肾功能不全时，t 1/2β从7小时仅增加至9小时，AUC有适度增加。药物的尿回收率随患者肌酐清除率的降低而成比例降低。因此，必须假定该利尿剂存在显著的肾外消除，这足以防止药物在肾衰竭时显著蓄积。
