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Furosemide disposition in cirrhosis
Author(s) -
Verbeeck Roger K,
Patwardhan Rashmi V,
Villeneuve JeanPierre,
Wilkinson Grant R,
Branch Robert A
Publication year - 1982
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1982.101
Subject(s) - furosemide , cirrhosis , ascites , volume of distribution , diuretic , disposition , medicine , pharmacokinetics , metabolite , clinical pharmacology , chlorothiazide , drug , endocrinology , pharmacology , psychology , social psychology
Furosemide disposition after rapid intravenous injection (80 mg) was studied in 10 normal healthy subjects and eight patients with cirrhosis and ascites. In the cirrhotic patients the elimination half‐life was modestly longer (81.0 ± 8.0 min and 60.2 ± 5.8 min). This prolongation was not associated with a difference in systemic clearance (156 ± 7 ml/min in normal and 142 ± 16 ml/min in cirrhotic subjects), rather it was a reflection of alterations in furosemide distribution. The steady‐state volume of distribution was increased from 8.5 ± 0.4 l in the healthy subjects to 12.1 ± 1.3 l in the cirrhotic subjects; estimation in terms of unbound drug indicated an approximately 50% smaller value in cirrhosis. These observations were quantitatively consistent with the increased percentage of furosemide in plasma in the unbound form in the patients (10.2 ± 1.0%) compared to in the normal subjects (4.0 ± 0.1%). The 24‐hr percentage urinary recovery of unchanged drug (58.8 ± 2.8% and 53.1 6.5%) and the glucuronide metabolite (17.8 ±7.5 and 21.3 ± 3.4) were on the same order in the normal and cirrhotic groups. The lack of major effects of cirrhosis on furosemide disposition suggests that changes in furosemide diuretic efficacy in such patients is a result of altered dynamic factors rather than altered disposition. Clinical Pharmacology and Therapeutics (1982) 31 , 719–725; doi: 10.1038/clpt.1982.101