Furosemide disposition in cirrhosis

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Abstract
Furosemide disposition after rapid i.v. injection (80 mg) was studied in 10 normal healthy subjects and 8 patients with cirrhosis and ascites. In the cirrhotic patients the elimination half-life was slightly longer (81.0 .+-. 8.0 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 in cirrhotic subjects); rather, it was a reflection of alterations in furosemide distribution. The steady-state volume of distribution was increased from 8.5 .+-. 0.41 in the healthy subjects to 12.1 .+-. 1.3 l in the cirrhotic subjects; estimation in terms of unbound drug indicated an .apprx. 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%) as compared to the normal subjects (4.0 .+-. 0.1%). The 24-h percentage urinary recovery of unchanged drug (58.8 .+-. 2.8 and 53.1 .+-. 6.5%) and the glucuronide metabolite (17.8 .+-. 1.5 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.