In:
Clinical Pharmacology & Therapeutics, Wiley, Vol. 24, No. 2 ( 1978-08), p. 199-207
Abstract:
The pharmacokinetic disposition of furosemide has been investigated in six normal subjects, 7 patients with the nephrotic syndrome and 6 patients with uremia. Furosemide levels were measured using a specific HPLC analytical procedure and protein binding was measured by equilibrium dialysis using 3 H‐furosemide. The high binding offurosemide in normal subjects (95.9 ± 0.1%) was reduced in both uremia (94.4 ± 0.4%) and the nephrotic syndrome (93.2 ± 0.5%). When alt three study groups were combined, furosemide binding correlated with the serum albumin concentration measured in each subject at the time of the study (r = −0.83, p 〈 0.001). Approximately 50% of the systemic clearance of total drug in controls (158 ± 11 ml/min) was due to renal clearance. The renal clearance of total furosemide in the nephrotic syndrome was not altered, but renal clearance of unbound drug decreased in proportion to the creatinine clearance. Extrarenal clearance was unaffected in the nephrotic syndrome. In contrast, in uremia, both renal and extrarenal clearances were significantly reduced. The fall in renal clearance was consistent with a reduction in functioning nephrons and the presence of competitive inhibitors for tubular secretion. The volume of distribution offurosemide at steady‐state correlated with both serum albumin (r= +0.73, p 〈 0.001) and drug binding (r = +0.63, p 〈 0.005) and was increased in the nephrotic syndrome. Furosemide half‐life was unchanged in nephrotic syndrome but prolonged by threefold in uremia. Chronic hemodialysis for two to four months in 4 of the uremic subjects produced no significant change in any pharmacokinetic parameter. This study indicates that the disposition of furosemide is not only dependent on renal function but also on the serum albumin concentration.
Type of Medium:
Online Resource
ISSN:
0009-9236
,
1532-6535
DOI:
10.1002/cpt.1978.24.issue-2
DOI:
10.1002/cpt1978242199
Language:
English
Publisher:
Wiley
Publication Date:
1978
detail.hit.zdb_id:
2040184-X
detail.hit.zdb_id:
123793-7
SSG:
15,3
