thromboxane-b2 and Hepatitis--Alcoholic

Urinary excretion of the vasoconstrictor metabolite thromboxane B2 is increased in some patients with the hepatorenal syndrome. To define the role of thromboxanes in this syndrome and to evaluate a potential treatment for the renal impairment, we administered the thromboxane synthetase inhibitor dazoxiben to 5 patients with alcoholic hepatitis and rapidly progressive renal failure. Dazoxiben 200 mg/day followed by 400 mg/day reduced urinary thromboxane B2 by approximately 50% without altering prostaglandin E2 or 6-keto prostaglandin F1 alpha and without improving creatinine clearance (6 +/- 2 to 6 +/- 3 ml/min). In 3 additional patients, a higher dose of dazoxiben of 600 mg/day reduced thromboxane B2 by approximately 75% without consistent improvement in renal function. Thus, as judged by selective thromboxane inhibition with dazoxiben, thromboxanes are unlikely to be the key renal vasoconstrictor factor in the hepatorenal syndrome.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Kidney Injury; Adult; Creatinine; Dinoprostone; Drug Evaluation; Hepatitis, Alcoholic; Humans; Imidazoles; Middle Aged; Oxidoreductases; Prostaglandins E; Syndrome; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes