Sjöström P, Beermann B, Odlind B
Scand J Urol Nephrol. 1987;21(1):55-64. doi: 10.3109/00365598709180292.
The pharmacokinetics of the loop diuretic piretanide and its diuretic effects were studied in 6 healthy volunteers, 12 pre-dialysis (GFR 7-28 ml/min) and 10 dialysis patients (c-creat. 1-7 ml/min). Single doses up to 96 mg i.v. and orally were well tolerated and audiometry showed no hearing changes. Pharmacokinetic data showed rapid and almost complete absorption (bioavailability 92%) and a rapid elimination with renal clearance of 50% of the total 200 ml/min in the normals and renal clearance of about 50% of actual GFR in the patients. Extrarenal clearance was the same in normals and patients. The rapid extrarenal elimination reduces the risk of accumulation in renal patients but also reduces the active fraction of the dosage being cleared by the kidneys. Therefore, a high dosage and high plasma levels of piretanide were necessary for diuretic effect in uremic patients. The relation between the urinary piretanide excretion rate and the chloruretic effect was similar in normals and uremic patients; Cl- excretion increased 40 mMol per mg piretanide excreted.
在6名健康志愿者、12名透析前患者（肾小球滤过率7 - 28 ml/分钟）和10名透析患者（肌酐清除率1 - 7 ml/分钟）中研究了髓袢利尿剂吡咯他尼的药代动力学及其利尿作用。静脉注射和口服高达96 mg的单剂量耐受性良好，听力测定显示听力无变化。药代动力学数据表明，药物吸收迅速且几乎完全（生物利用度92%），消除迅速，正常人体内肾脏清除率占总清除率200 ml/分钟的50%，患者体内肾脏清除率约占实际肾小球滤过率的50%。正常人和患者的肾外清除率相同。肾外快速消除降低了肾病患者体内药物蓄积的风险，但也降低了经肾脏清除的活性药物部分。因此，对于尿毒症患者，需要高剂量和高血浆浓度的吡咯他尼才能产生利尿作用。正常人和尿毒症患者尿液中吡咯他尼排泄率与利尿效果之间的关系相似；每排泄1 mg吡咯他尼，氯离子排泄量增加40 mmol。
