title: Altered furosemide pharmacokinetics in chronic alcoholic liver disease with ascites contributes to diuretic resistance.
abstract: Some patients with chronic alcoholic liver disease and ascites have an impaired natriuretic response to furosemide. To elucidate the mechanism of this diuretic resistance, we measured para-aminohippurate and inulin clearances and urinary excretion of electrolytes, prostaglandin E2, and furosemide after intravenous administration of 80 mg of furosemide in 26 patients. The natriuretic response was variable (3.3-172 mEq/h) and was unrelated to basal sodium excretion, renal clearances, or urinary prostaglandin E2. Natriuresis correlated negatively with plasma aldosterone (r = -0.54, p less than 0.01), and strongly with urinary furosemide (range 5.5-76 mg/h, r = 0.71, p less than 0.001). As urinary furosemide excretion reflects the amount of furosemide reaching the active site on the luminal side of the tubule, the data demonstrate markedly reduced amounts of furosemide at its primary site of action in patients with diuretic resistance. Plasma furosemide was higher in patients with reduced furosemide excretion and impaired natriuresis, suggesting that the defect was an impairment of furosemide transport into the tubule. Thus, a major factor in diuretic resistance is altered furosemide pharmacokinetics.
authors.forename: M
authors.initials: M
authors.lastname: Pinzani
authors.forename: G
authors.initials: G
authors.lastname: Daskalopoulos
authors.forename: G
authors.initials: G
authors.lastname: Laffi
authors.forename: P
authors.initials: P
authors.lastname: Gentilini
authors.forename: R D
authors.initials: RD
authors.lastname: Zipser
mesh_terms: D015232:Dinoprostone; D004351:Drug Resistance; D005665:Furosemide / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D007444:Inulin; D007700:Kinetics; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy*; D009318:Natriuresis / Q000187:drug effects*; D011458:Prostaglandins E / Q000652:urine; D010130:p-Aminohippuric Acid
chemical_list: D011458:Prostaglandins E; D005665:Furosemide; D007444:Inulin; D015232:Dinoprostone; D010130:p-Aminohippuric Acid