Furosemide kinetics in renal failure

Tilstone, W. J.; Fine, Adrian

doi:10.1002/cpt1978236644

Cited by 80 publications

(27 citation statements)

References 3 publications

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“…Regarding the pharmacology, intestinal reabsorption of 40 -90% has been reported in subjects with advanced CKD (65), yet altogether reabsorption seems diminished (154). Although a clear relationship between reabsorption and measures of GFR has not been documented in CKD, this could contribute to furosemide resistance.…”

Section: Does Kidney Disease Affect the Actions Of Furosemide?mentioning

confidence: 99%

Everything we always wanted to know about furosemide but were afraid to ask

Huang

Mees

Vos

et al. 2016

American Journal of Physiology-Renal Physiology

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Huang X, Dorhout Mees E, Vos P, Hamza S, Braam B. Everything we always wanted to know about furosemide but were afraid to ask. Am J Physiol Renal Physiol 310: F958 -F971, 2016. First published February 24, 2016 doi:10.1152/ajprenal.00476.2015.-Furosemide is a widely used, potent natriuretic drug, which inhibits the Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC)-2 in the ascending limb of the loop of Henle applied to reduce extracellular fluid volume expansion in heart and kidney disease. Undesirable consequences of furosemide, such as worsening of kidney function and unpredictable effects on sodium balance, led to this critical evaluation of how inhibition of NKCC affects renal and cardiovascular physiology. This evaluation reveals important knowledge gaps, involving furosemide as a drug, the function of NKCC2 (and NKCC1), and renal and systemic indirect effects of NKCC inhibition. Regarding renal effects, renal blood flow and glomerular filtration rate could become compromised by activation of tubuloglomerular feedback or by renin release, particularly if renal function is already compromised. Modulation of the intrarenal renin angiotensin system, however, is ill-defined. Regarding systemic effects, vasodilation followed by nonspecific NKCC inhibition and changes in venous compliance are not well understood. Repetitive administration of furosemide induces short-term (braking phenomenon, acute diuretic resistance) and long-term (chronic diuretic resistance) adaptations, of which the mechanisms are not well known. Modulation of NKCC2 expression and activity in kidney and heart failure is ill-defined. Lastly, furosemide's effects on cutaneous sodium stores and on uric acid levels could be beneficial or detrimental. Concluding, a considerable knowledge gap is identified regarding a potent drug with a relatively specific renal target, NKCC2, and renal and systemic actions. Resolving these questions would increase the understanding of NKCCs and their actions and improve rational use of furosemide in pathophysiology of fluid volume expansion. extracellular fluid volume; natriuresis; renal function; chronic kidney disease; heart failure DIURETICS BLOCKING THE Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC) have an important place in the treatment of fluid overload, specifically in the context of kidney disease and heart failure (64). Of the drugs that inhibit the NKCC2 in the loop of Henle (furosemide, bumetanide, torsemide, ethacrynic acid), furosemide is most commonly applied (66) and Ͼ40 million prescriptions are dispensed every year in the USA (66a). However, many uncertainties remain about intrarenal and systemic actions of furosemide, including its two main targets NKCC1 and NKCC2.Clinically, there are a number of undesirable consequences of the use of furosemide, of which the pathophysiological mechanisms have not been sufficiently investigated. Furosemide has been associated with worsening of kidney function in patients treated for volume overload admitted for acute heart failure (104) and even glomerular filtration rate (GFR) ...

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Section: Does Kidney Disease Affect the Actions Of Furosemide?mentioning

confidence: 99%

Everything we always wanted to know about furosemide but were afraid to ask

Huang

Mees

Vos

et al. 2016

American Journal of Physiology-Renal Physiology

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“…Whilst a number of pathophysiological factors such as gastro-intestinal oedema, gut motility and local blood flow at the absorption site may be contributory factors to this reduction in bioavailability, the decrease is less than has been observed for frusemide. In studies with frusemide in patients with advanced renal failure, values of 0.43 (Tilstone & Fine, 1978) and 0.46 (Rane et al, 1978) were reported.…”

Section: Pharmacokineticsmentioning

confidence: 99%

The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease.

Marcantonio¹,

Auld²,

Murdoch³

et al. 1983

Brit J Clinical Pharma

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1Bumetanide (1 mg) was given orally and intravenously to a group of patients with chronic renal failure (n = 6) and to another group with cirrhosis of the liver (n = 8). 2 The pharmacokinetics, using a two-compartment model, and the pharmacodynamics of the drug in these patients were compared with those previously obtained for normal subjects. 3 In the renal group serum bumetanide concentrations were higher than for the normal subjects and the terminal half-lives were significantly prolonged (P < 0.001). A decreased whole body clearance was attributable to a low renal clearance of drug, the non-renal clearance being significantly increased (P < 0.01). 4 For the patients with liver disease, serum bumetanide concentrations were higher than for the renal group, and the terminal half-lives were significantly further prolonged (P < 0.001). Both non-renal and renal clearances were significantly reduced (P < 0.001). 5 Absorption rates were not significantly altered in either group and the values of F (bioavailability) were 0.82 and 0.95 for the patients with renal disease and hepatic disease, respectively. 6 A poor pharmacodynamic response and a reduced bumetanide excretion rate were observed for the patients with chronic renal failure, whereas with hepatic disease normal bumetanide excretion rates were observed with an impaired diuretic response.

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“…It is highly bound to plasma proteins (6)(7)(8)(9)(10)(11)(12) and gains access to its site of action in the kidney lumen primarily through active secretion via the nonspecific organic acid secretory pathway (13)(14)(15). Previous studies have shown that renal disease can effect dramatic changes in the pharmacokinetics of furosemide (6,11,(16)(17)(18)(19)(20), including impaired plasma protein binding in uremics (7,11), nephrotics (10,11), and anephric patients (6). The degree of binding of furosemide to plasma proteins in kidney transplant patients has not been reported.…”

Section: Introductionmentioning

confidence: 99%