Branch R A
Fed Proc. 1983 Apr;42(6):1699-702.
Furosemide is an acidic drug that binds tightly to anionic binding sites on albumin, but has negligible binding to tissue proteins. As a consequence, it has a low volume of distribution of total drug at steady state (Vdss total), which is less than extracellular fluid volume. With decreases in serum albumin concentration, plasma protein binding decreases, total Vdss increases, and Vdss of free drug decreases in a manner that is quantitatively consistent with no change in tissue binding. The elimination of furosemide is partly by renal clearance of unchanged drug (predominantly because of renal tubule secretion) and partly by nonrenal routes. Glucuronidation appears to occur in extrahepatic sites in dogs and, possibly, humans. Residual nonrenal elimination is not influenced by liver disease but is reduced by probenecid pretreatment and uremia. Furthermore, there is appreciable recovery of 35S-labeled furosemide in feces after i.v. administration without the appearance of 35S in the bile. These observations are consistent with the hypothesis of active secretion of furosemide into the gut. The independent variables of distribution and elimination contribute to determine intersubject variability of plasma concentration-time profiles in health and disease and, therefore, are important in determining the extent and duration of diuretic response.
呋塞米是一种酸性药物，它与白蛋白上的阴离子结合位点紧密结合，但与组织蛋白的结合可忽略不计。因此，其稳态时总药物的分布容积（Vdss总）较低，小于细胞外液容积。随着血清白蛋白浓度降低，血浆蛋白结合减少，总Vdss增加，游离药物的Vdss降低，其方式在数量上与组织结合无变化一致。呋塞米的消除部分通过未改变药物的肾清除（主要由于肾小管分泌），部分通过非肾途径。葡糖醛酸化似乎发生在犬类以及可能在人类的肝外部位。残余的非肾消除不受肝脏疾病影响，但丙磺舒预处理和尿毒症会使其降低。此外，静脉注射后粪便中可明显回收35S标记的呋塞米，而胆汁中未出现35S。这些观察结果与呋塞米向肠道的主动分泌假说一致。分布和消除的独立变量有助于确定健康和疾病状态下血浆浓度-时间曲线的个体间变异性，因此在确定利尿反应的程度和持续时间方面很重要。
