Pharmacokinetics of furosemide in man after intravenous and oral administration. Application of moment analysis

Hammarlund, Margareta; Paalzow, Lennart; Odlind, Bo

doi:10.1007/bf00630286

Cited by 113 publications

(92 citation statements)

References 15 publications

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“…Furosemide strongly binds to plasma proteins (91-99%) (34), particularly to anionic sites on albumin (20). Most intestinal furosemide absorption occurs in the stomach and small intestine (30,58,160). Although the mean availability of oral furosemide is ϳ60%, absorption ranges from 10 -100%.…”

Section: Pharmacology Pharmacodynamics Pharmacokinetics Of Furosemidementioning

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: Pharmacology Pharmacodynamics Pharmacokinetics Of Furosemidementioning

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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“…[5][6][7][8][9] There are several administration routes for furosemide, including IV, PO, SC, and IM. Pharmacokinetics of furosemide has been compared between IV and PO administration.…”

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confidence: 99%

“…Pharmacokinetics of furosemide has been compared between IV and PO administration. 9 However, the effects of furosemide on LAP in dogs with MR have not been well documented in a quantitative manner because there are some difficulties in measuring LAP directly. We have previously reported the 24-hour LAP profiles of and the effect of angiotensin-converting enzyme (ACE) inhibitors on experimentally induced MR dogs with a radio telemetry system.…”

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confidence: 99%

The Effect of Furosemide on Left Atrial Pressure in Dogs with Mitral Valve Regurgitation

Suzuki¹,

Ishikawa²,

Hamabe³

et al. 2011

Veterinary Internal Medicne

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Background: The effects of furosemide on left atrial pressure (LAP) in dogs with mitral regurgitation (MR) have not been documented in a quantitative manner and between different routes of administration.Objective: To document LAP and echocardiographic parameters in MR dogs administered furosemide IV or PO, in order to document changes in LAP after furosemide treatment.Animals: Five healthy Beagle dogs (3 males and 2 females; aged 2 years) were used. Methods: Experimental, cross-over, and interventional study. LAP was measured before the administration of furosemide, and 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours after administration. Furosemide 1, 2, or 4 mg/kg IV, PO or placebo was administered.Results: LAP was significantly decreased with all administrations of furosemide but not after placebo (P o .05, respectively). The max reduction was observed 1 hour (1 mg/kg IV, 15.04 AE 7.02 mmHg), 3 hours (2, 4 mg/kg IV, 13.28 AE 8.01, 9.23 AE 4.92 mmHg), 4 hours (1 mg/kg PO, 14.68 AE 11.51 mmHg), and 5 hours (2, 4 mg/kg PO, 13.19 AE 10.52, 10.70 AE 7.69 mmHg). E wave and E/Ea were significantly decreased corresponding to the reduction of LAP after administration of 2 and 4 mg/kg (P o .05, respectively).Conclusions and Clinical Importance: LAP was decreased in proportion to the dosage of furosemide, which did not significantly differ between IV and PO of the same dosages. E wave and E/Ea might be useful for the treatment evaluation of furosemide.Key words: Radio telemetry system; Total circulating blood volume; Transmitral blood flow.M itral valve disease is the most common cardiac disease in dogs. As many as three quarters of all dogs with signs of congestive heart failure suffer from mitral regurgitation (MR) caused by myxomatous degeneration of the valve leaflets or the chordae tendineae.1,2 MR increases the left atrial pressure (LAP) which potentially results in left atrial dilation. Elevated LAP causes pulmonary edema that can lead to cough, dyspnea, and even death.3 Therefore, LAP needs to be reduced to avoid these clinical signs.Furosemide, a loop diuretic, has a strong diuretic effect and is commonly used for the treatment of pulmonary edema in patients with MR. 4 Furosemide reduces the total circulating blood volume, which in turn reduces the LAP or the left ventricular filling pressure, and leads to the clinical improvement of the patients. [5][6][7][8][9] There are several administration routes for furosemide, including IV, PO, SC, and IM. Pharmacokinetics of furosemide has been compared between IV and PO administration. However, the effects of furosemide on LAP in dogs with MR have not been well documented in a quantitative manner because there are some difficulties in measuring LAP directly. We have previously reported the 24-hour LAP profiles of and the effect of angiotensin-converting enzyme (ACE) inhibitors on experimentally induced MR dogs with a radio telemetry system. 10,11 The previous study has demonstrated that this system is useful for the evaluation of hemodynamic changes that occur...

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“…lntroduet|on. It is well known that furans exhibit pharmacological activity and many of them are in use as pharmaceuticals (Martorana, Share & Zimmerman, 1985;Hammarlund, Odlind & Paalzow, 1985), herbicides (Melhus, 1935), fungicides (Koschucharoff & Harisanowa, 1962), bactericides (Ascoli, Casini, Ferappi & Tubaro, 1967), etc.…”

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confidence: 99%