Food: an unrecognized source of loop diuretic resistance.

Food significantly affects the pharmacokinetics of oral loop diuretics in healthy individuals, but studies have not been performed in patients with edema. Because of this omission, food's effect on pharmacokinetics has been overlooked and may decrease the pharmacodynamic response in patients who rely on diuretics. Despite this potential interaction, reference manuals do not provide warnings about the effects of food on loop diuretic absorption. We reviewed the published human studies investigating the effects of food on loop diuretics. Peak plasma concentrations and urinary recovery were significantly decreased when taken with food, but only one study showed a corresponding decrease in total urine output, which is likely related to the diuretic threshold effect. These healthy subjects probably were always above the diuretic threshold under both fed and fasting conditions and thus could not augment their urine output. Based on these data in healthy subjects, the special implications for patients who routinely take diuretics are discussed. Therefore, food is more likely to have a clinical effect on the diuretic threshold given its effect in healthy subjects and the special considerations for patients with edema. Additional studies are needed to help answer these questions. Until such data are available, the most conservative, effective clinical approach is to administer oral loop diuretics without food.