PHARMACOKINETICS AND DYNAMICS OF FUROSEMIDE IN MAN

呋塞米在人体内的药代动力学和动力学

• 批准号: 3237078
• 负责人: D CRAIG BRATER
• 金额: $ 27.48万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-03-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3237078
• 关键词: acetazolamide; aminophylline; antiinflammatory agents; ascites; chromatography; chronic disease /disorder; combination chemotherapy; computer simulation; congestive heart failure; diuretics; dosage; drug adverse effect; drug metabolism; drug receptors; drug resistance; furosemide; hemodynamics; high performance liquid chromatography; human subject; indomethacin; kidney metabolism; kidney pharmacology; laboratory rabbit; liver cirrhosis; liver disorder; membrane permeability; nephrotic syndrome; passive transport; pharmacokinetics; probenecid; prostaglandins; radioimmunoassay; renal failure; renal tubular transport; saluresis; scintillation counter; scintillation spectrometry; solute; spironolactone; urinalysis

Our laboratory has explored the determinants of response to diuretics in both normal conditions and in diseases in which response is altered. Data focused on patients with heart failure showing delayed absorption of furosemide after oral dosing, normal quantitative absorption, normal renal clearance, and suppressed response relative to amounts of diuretic reaching the site of action. Future studies will examine patients with renal insufficiency, particularly addressing the question of whether response of individual nephrons to amounts of diuretic reaching them is normal. We will also study patients with nephrotic syndrome addressing whether or not binding of diuretic to urinary protein is an important contributor to diuretic resistance in these patients. Our laboratory has also studied the renal role of prostaglandins, exploring effects of nonsteroidal anti-inflammatory drugs on renal function. Prior studies by us have questioned the putative renal sparing effect of sulindac. We wish to explore this area further with pharmacokinetic and pharmacodynamic studies in patients with cirrhosis. We have also assessed the effects of indomethacin in patients with renal insufficiency and in preliminary studies found it to transiently and reversibly decrease renal perfusion. We wish to determine whether continuous suppression of renal prostaglandins causes persistent effects. We have learned the technique of microperfusion of isolated nephron segments to assess handling of nonsteroidal anti-inflammatory (and other) drugs by the kidney. Preliminary data have shown substantial secretion of indomethacin by the proximal tubule and considerable formation of indomethacin glucuronide. It would appear that transport of this drug may represent a two step process. We propose further pursuit of these questions.

我们的实验室探讨了对利尿剂的反应的决定因素 正常情况和反应改变的疾病。 数据 专注于心力衰竭的患者，显示出延迟的吸收 口服剂量后的速尿，正常定量吸收，正常肾脏 间隙和相对于利尿剂达到量的抑制反应 行动地点。 未来的研究将检查肾脏患者 不足，尤其是解决了是否回应的问题 单个肾肾脏达到的利尿剂量是正常的。 我们 还将研究肾病综合征患者 利尿剂与尿蛋白的结合是造成的重要促进者 这些患者的利尿剂耐药性。 我们的实验室还研究了前列腺素的肾作用，探索 非甾体类抗炎药对肾功能的影响。 事先的 我们的研究质疑 Sulindac。 我们希望通过药代动力学和 肝硬化患者的药效研究。 我们还评估了 吲哚美辛对肾功能不全患者的影响 初步研究发现它可以瞬时和可逆地减少肾脏 灌注。 我们希望确定是否连续抑制肾脏 前列腺素会引起持续的影响。 我们学会了孤立肾单位的微灌注技术 评估对非甾体类抗炎（和其他）处理的细分市场 肾脏的毒品。 初步数据显示了 近端小管的吲哚美辛和相当大的形成 吲哚美辛葡萄糖醛酸。 看来这种药物的运输可能 表示两个步骤。 我们建议进一步追求这些 问题。