Food: An Unrecognized Source of Loop Diuretic Resistance

Abstract

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.

Interplay of Breast Cancer Resistance Protein (Bcrp/Abcg2), Sex, and Fed State in Oral Pharmacokinetic Variability of Furosemide in Rats

“…Despite conflicting reports of food-effect on FUR PK, majority of the studies reveal a negative food-effect for FUR in humans [ 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. For example, a 30% decrease in FUR bioavailability is reported in humans after food [ 60 ].…”

Acidic urine as a novel risk factor for diuretic resistance and worse in-hospital prognosis in acute heart failure

“…HF and diet can prolong the time to peak concentration and peak drug levels. [31] Taking into account the fact that LD are 95% protein bound, hypoalbuminemia increases the volume of distribution and reduces the availability of LD for facilitated diffusion. Uremic toxins and nonsteroidal antiinflammatory drugs can also inhibit drug transport across proximal tubular epithelial cells.…”

Relieving the tension in hypertension: Food–drug interactions and anti‐hypertensive mechanisms of food bioactive compounds

“…Loop diuretics (Furosemide) when taken together with food, it decreases the bioavailability of these drugs (with a decrease seen between 16%-45%) while Bumetanide reflect no changes in availability when administered with food (McCrindle, Li kam wa, Barron, & Prescott, 1996). The decrease in bioavailability of loop diuretics when administered orally with food is affirmed with a single study found used to relate the threshold of the diuretic effectiveness as a result of a decrease in urinary excretion of these drugs after food intake (Bard, Bleske, & Nicklas, 2004). Accordingly, Jáuregui- et al (2012) revealed that it is important to increase the bioavailability of hydrochlorothiazide in rats that are protein-calorie malnourished due to a decrease in the gastrointestinal and hepatic metabolism since Hydrochlorothiazide (a thiazide diuretic) have increased bioavailability with food.…”