Pharmacokinetics and metabolism of furosemide in man

Prandota, J; Witkowska, M

doi:10.1007/bf03189275

Cited by 17 publications

(7 citation statements)

References 19 publications

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“…The liver appears to play a minor role in the metabolism of furosemide and an indirect evidence suggests that the kidneys could metabolize this compound [ 87 ]. The only known metabolite is the 4-chloro-5-sulfamoylantranilic acid, which has also a potential diuretic activity [ 88 ].…”

Section: Diureticsmentioning

confidence: 99%

Antihypertensive Drugs Metabolism: An Update to Pharmacokinetic Profiles and Computational Approaches

Zisaki¹,

Mišković²,

Hatzimanikatis³

2014

CPD

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Drug discovery and development is a high-risk enterprise that requires significant investments in capital, time and scientific expertise. The studies of xenobiotic metabolism remain as one of the main topics in the research and development of drugs, cosmetics and nutritional supplements. Antihypertensive drugs are used for the treatment of high blood pressure, which is one the most frequent symptoms of the patients that undergo cardiovascular diseases such as myocardial infraction and strokes. In current cardiovascular disease pharmacology, four drug clusters - Angiotensin Converting Enzyme Inhibitors, Beta-Blockers, Calcium Channel Blockers and Diuretics - cover the major therapeutic characteristics of the most antihypertensive drugs. The pharmacokinetic and specifically the metabolic profile of the antihypertensive agents are intensively studied because of the broad inter-individual variability on plasma concentrations and the diversity on the efficacy response especially due to the P450 dependent metabolic status they present. Several computational methods have been developed with the aim to: (i) model and better understand the human drug metabolism; and (ii) enhance the experimental investigation of the metabolism of small xenobiotic molecules. The main predictive tools these methods employ are rule-based approaches, quantitative structure metabolism/activity relationships and docking approaches. This review paper provides detailed metabolic profiles of the major clusters of antihypertensive agents, including their metabolites and their metabolizing enzymes, and it also provides specific information concerning the computational approaches that have been used to predict the metabolic profile of several antihypertensive drugs.

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Section: Diureticsmentioning

confidence: 99%

Antihypertensive Drugs Metabolism: An Update to Pharmacokinetic Profiles and Computational Approaches

Zisaki¹,

Mišković²,

Hatzimanikatis³

2014

CPD

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“…administration 74,75 . Moreover, Furosemide displays a first pass effect by undergoing enzymatic deactivation in liver 76,77 . Thus, its p.o.…”

Section: Furosemidementioning

confidence: 99%

Mucosal delivery systems of antihypertensive drugs: A practical approach in general practice

Biały¹,

Wojcik²,

Młynarczuk-Biały³

2018

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Patients who are unable to receive oral medication (p.o.) are a major problem in outpatient settings, especially in home health care systems. Mucosal administration of drugs offers an alternative to the oral route, especially when the parenteral mode cannot be used. There are three main pathways of mucosal administration: sublingual/buccal, intranasal and rectal. We discuss the possibility of mucosal delivery of antihypertensive drugs. Perindopril arginine and Amlodipine besylate are registered in the EU as orodispersible tablets for oromucosal delivery, however, they are not available in all countries. For this reason, we describe other drugs suitable for mucosal delivery: Captopril and Nitrendipine in the sublingual system and Metoprolol tartrate, Propranolol and Furosemide by the transrectal route. Based on the published data and common clinical practice we discuss the use of mucosal delivery systems of all these antihypertensive drugs with special attention to their pharmacokinetics. We illustrate this mini-review with a case report of the prolonged-term use of mucosal delivery of sublingual Captopril and Nitrendipine combined with rectal Metoprolol tartrate and Furosemide in a patient with severe hypertension unable to receive medication p.o. This is also a report on the first human use of Furosemide-containing suppositories as well as prolonged-term transmucosal administration of these four drugs, describing a practical approach leading to successful control of severe hypertension with four antihypertensive drugs delivered via the mucosal route. The treatment was effective and without side effects; however, the long-term safety and efficacy of such therapy must be confirmed by randomized clinical trials.

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“…Furosemide (4-chloro-5-sulfamoyl-N-furfuryl-anthranilic acid; Scheme 1), a loop diuretic drug, is used to treat edema due to heart failure, liver dysfunction, or kidney disease. 16 Furosemide is a structural analogue of 3-hydroxyanthranilic acid, a product of tryptophan metabolism and a known endogenous regulator of inflammation. 17 Furosemide exhibits anti-inflammatory activity by inhibiting the production and release of cytokines including IL-6, IL-8, and TNF-α from peripheral mononuclear cells.…”

Section: ■ Introductionmentioning

confidence: 99%

Furosemide as a Probe Molecule for the Treatment of Neuroinflammation in Alzheimer’s Disease

Wang

Vilekar

Huang

et al. 2020

ACS Chem. Neurosci.

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The accumulation and deposition of β-amyloid (Aβ) is one postulated cause of Alzheimer’s disease (AD). In addition to its direct toxicity on neurons, Aβ may induce neuroinflammation through the concomitant activation of microglia. Emerging evidence suggests that microglia-mediated neuroinflammation plays an important role in the pathogenesis of AD. As brain macrophages, microglia engulf misfolded-Aβ by phagocytosis. However, the accumulated toxic Aβ may paradoxically “hyper-activate” microglia into a neurotoxic proinflammatory and less phagocytotic phenotype, contributing to neuronal death. This study reports that the known drug furosemide is a potential probe molecule for reducing AD-neuroinflammation. Our data demonstrate that furosemide inhibits the secretion of proinflammatory TNF-α, IL-6, and nitric oxide; downregulates the mRNA level of Cd86 and the protein expression of COX-2, iNOS; promotes phagocytic activity; and enhances the expression of anti-inflammatory IL-1RA and arginase. Our mechanism of action studies further demonstrate that furosemide reduces LPS-induced upregulation of endoplasmic reticulum (ER) stress marker genes, including Grp78, Atf4, Chop, tXbp1, and sXbp1. These data support the observation that furosemide is a known drug with the capacity to downregulate the proinflammatory microglial M1 phenotype and upregulate the anti-inflammatory M2 phenotype, a potentially powerful and beneficial pharmacologic effect for inflammatory diseases such as AD.

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Pharmacokinetics and metabolism of furosemide in man

Cited by 17 publications

References 19 publications

Antihypertensive Drugs Metabolism: An Update to Pharmacokinetic Profiles and Computational Approaches

Antihypertensive Drugs Metabolism: An Update to Pharmacokinetic Profiles and Computational Approaches

Mucosal delivery systems of antihypertensive drugs: A practical approach in general practice

Furosemide as a Probe Molecule for the Treatment of Neuroinflammation in Alzheimer’s Disease

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