Therapeutic trial of thromboxane synthesis inhibition in the hepatorenal syndrome.
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.
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000652:urine; D000328:Adult; D003404:Creatinine / Q000378:metabolism; D015232:Dinoprostone; D004341:Drug Evaluation; D006519:Hepatitis, Alcoholic / Q000188:drug therapy* / Q000652:urine; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008875:Middle Aged; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011458:Prostaglandins E / Q000652:urine; D013577:Syndrome; D013929:Thromboxane B2 / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013931:Thromboxanes / Q000096:biosynthesis*
D007093:Imidazoles; D011458:Prostaglandins E; D013931:Thromboxanes; C029166:dazoxiben; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003404:Creatinine; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase; D015232:Dinoprostone