sUA levels, fractional excretion of uric acid (FEUA), lesinurad plasma levels, and urinary excretion of lesinurad were measured in healthy volunteers treated with lesinurad. 2016 Mar;76(4):509-16. doi: 10.1007/s40265-016-0550-y. Saag KG, Fitz-Patrick D, Kopicko J et al. Lesinurad in combination with allopurinol therefore provides a dual mechanism of action for managing the hyperuricemia of gout: increased urinary excretion of ⦠http://www.ncbi.nlm.nih.gov/pubmed/26742777?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4893096&blobtype=pdf, 4. URAT1 is a major transporter enzyme responsible for reuptake of uric acid from the renal tubules; inhibition of URAT1 function thereby increases excretion of uric acid. During evolution, humans lost the enzyme uricase 2. 1 5 10 Combined use with a xanthine oxidase inhibitor, which blocks uric acid production, reduces the amount of uric acid available for excretion and decreases the risk of ⦠Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol. Lesinurad inhibits the activity of uric acid transporter 1 (URAT1) and organic anion transporter 4 (OAT4). 2015; 27:164-9. http://www.ncbi.nlm.nih.gov/pubmed/25603039?dopt=AbstractPlus, 7. Zurampic (lesinurad) tablets prescribing information. ), Headache,1 10 influenza,1 increased Scr,1 10 GERD.1, Metabolized principally by CYP2C9.1 Weak inducer of CYP3A; causes no clinically important induction of CYP1A2, 2B6, 2C8, 2C9, or 2C19 and no clinically important inhibition of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4.1, Substrate for OAT1 and OAT3 in vitro, but no clinical interaction studies to date with OAT1 and OAT3 inhibitors.1, Inhibitor of organic anion transporter protein (OATP) 1B1, OAT1 and OAT3, and organic cation transporter 1 (OCT1) in vitro but not in vivo.1 No clinically important effect on P-glycoprotein in vitro.1, CYP2C9 inhibitors: Increased lesinurad exposure.1 Use lesinurad and moderate CYP2C9 inhibitors concomitantly with caution.1, Moderate CYP2C9 inducers: Decreased exposure and possible reduced efficacy of lesinurad.1, CYP3A substrates: Possible decreased plasma concentrations of sensitive CYP3A substrates.1 9 Consider possible reduced efficacy of CYP3A substrate drugs and monitor for efficacy.1 9, Amlodipine AUC and peak plasma concentration decreased by about 40%1 7, Monitor for possible reduced efficacy of amlodipine1, Antacids (aluminum and magnesium hydroxides, calcium carbonate), No substantial effect on AUC or peak plasma concentration of lesinurad1, Aspirin may alter URAT1 inhibitory effects of lesinurad7, Aspirin (>325 mg daily): Possible reduced lesinurad efficacy1, Aspirin (≤325 mg daily): No evidence in clinical trials of reduced lesinurad efficacy1 9, Lesinurad and aspirin at dosages ≤325 mg daily (i.e., for cardiovascular protection) may be used concomitantly1 9, Possible decreased exposure and decreased efficacy of lesinurad1, No substantial effect on colchicine pharmacokinetics1 7, Epoxide hydrolase inhibitors (e.g., valproic acid), Possible interference with lesinurad metabolism1, Lesinurad AUC and peak plasma concentration increased by 56 and 38%, respectively1 7, Furosemide AUC and peak plasma concentration decreased by 31 and 51%, respectively, but no change in diuretic activity1 7, HMG-CoA reductase inhibitors (statins) (e.g., atorvastatin), No substantial change in atorvastatin exposure; possible decreased exposure to statins that are more sensitive CYP3A substrates 1 7 9, Atorvastatin: No dosage adjustment necessary1, Consider potential for reduced efficacy of statins that are sensitive CYP3A substrates and monitor for efficacy1, Hormonal contraceptives (oral, injectable, transdermal, implants), Possible decreased plasma concentrations and decreased efficacy of the contraceptive1 9, Do not rely solely on hormonal contraceptives; use additional methods of contraception1, No change in metformin AUC or peak plasma concentration1, Indomethacin, naproxen: No substantial effect on pharmacokinetics of lesinurad or the NSAIA1 7, No substantial effect on lesinurad pharmacokinetics1, No substantial effect on AUC or peak plasma concentration of repaglinide1, Lesinurad AUC and peak plasma concentration decreased by 38 and 24%, respectively1 7 9, Monitor for possible reduced efficacy of lesinurad1, Sildenafil AUC and peak plasma concentration decreased by about 34%1 7, Monitor for possible reduced efficacy of sildenafil1, No substantial effect on AUC or peak plasma concentration of tolbutamide1, No substantial effect on warfarin pharmacokinetics (AUC, peak plasma concentration) or pharmacodynamics (INR)1 7, Xanthine oxidase inhibitors (allopurinol, febuxostat), Allopurinol, febuxostat: No substantial effect on pharmacokinetics of lesinurad or the xanthine oxidase inhibitor7, Differing mechanisms of action used to therapeutic advantage in lowering elevated serum uric acid concentrations in patients with gout1 7 9, Rapidly and completely absorbed following oral administration.1 7, Peak plasma concentration attained within 1–4 hours under fasted or fed conditions.1, Peak plasma concentration and AUC increase in a dose-dependent manner.1, Administration with a high-fat meal reduces peak plasma concentration by up to 18% but does not alter AUC.1, Mild or moderate (Child-Pugh class A or B) hepatic impairment: AUC increased by 7 or 33%, respectively, compared with individuals with normal hepatic function.1, Mild, moderate, or severe renal impairment: AUC increased by 30, 50–73, or 113%, respectively, compared with individuals with normal renal function.1, Poor CYP2C9 metabolizers: Exposure increased by approximately 1.8-fold compared with extensive metabolizers.1, Not known whether distributed into human milk.1, Renal or hepatic impairment does not substantially alter plasma protein binding of lesinurad.1, 63 and 32% of radiolabeled dose recovered in urine and feces, respectively.1 Unchanged lesinurad in urine accounted for approximately 30% of administered dose.1, 20–25°C (may be exposed to 15–30°C).1 Protect from light.1, Reduces serum uric acid concentrations via inhibition of URAT1 and OAT4, 2 apical transporter proteins in the OAT family6 involved in renal reabsorption of uric acid.1 8 URAT1 accounts for majority of reabsorption of filtered uric acid from renal tubular lumen;1 OAT4 is associated with diuretic-induced hyperuricemia.1 8, Does not inhibit glucose transporter 9 (GLUT9), a uric acid reabsorption transporter located on the basolateral membrane of the proximal tubule cell.1 5 8, More selective than probenecid, which inhibits URAT1, OAT4, and other OAT family members (OAT1 and OAT3) in the clinical setting.2 8, Increases renal clearance and fractional excretion of uric acid and lowers serum uric acid concentrations in a dose-dependent manner in patients with gout.1 Combined use with a xanthine oxidase inhibitor, which blocks uric acid production, reduces amount of uric acid available for excretion and decreases risk of adverse renal effects.4 9, Importance of reading the manufacturer's medication guide before beginning lesinurad therapy and each time the prescription is refilled.1, Importance of using lesinurad concomitantly with a xanthine oxidase inhibitor and of discontinuing lesinurad if the xanthine oxidase inhibitor is discontinued.1 Advise patients to take lesinurad in the morning with food and water at the same time as the xanthine oxidase inhibitor and to stay well-hydrated (e.g., by drinking 2 L [68 ounces] of fluids daily).1, Importance of informing patients that if a dose of lesinurad is missed, not to take the missed dose later in the day.1 Advise patients to omit the missed dose and resume the regular dosing schedule the following day; instruct patients to not double the dose.1, Risk of adverse renal effects (e.g., transient increases in Scr, renal stones, acute renal failure); importance of periodic monitoring of Scr.1, Potential for gout flares to occur following initiation of lesinurad therapy; importance of receiving prophylactic therapy for gout flares upon initiation of lesinurad.1 Advise patients not to discontinue lesinurad if a gout flare occurs during treatment.1, Importance of informing women of childbearing potential not to rely solely on hormonal contraceptives and to use additional methods of contraception when receiving lesinurad.1, Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1, Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1, Importance of informing patients of other important precautionary information.1 (See Cautions.). Zurampic (lesinurad) tablets. patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone. From FDA website. For these patients, combining two therapies with complementary mechanisms of action represents a promising approach to achieving target sUA without the need for allopurinol dose uptitration. In August 2017, a combination oral therapy consisting of lesinurad and Allopurinol was FDA-approved under the brand name Duzallo indicated for the treatment of gout-related hyperuricemia in patients with uncontrolled gout. Last updated on March 12, 2020. As a potentially nephrotoxic uricosuric drug acting on the kidney, nephrologists should become familiar with its indications and safety profile. Within 7 days following single dosing of radiolabeled lesinurad, 63% of administered radioactive dose was recovered in urine and 32% of administered radioactive dose was recovered in feces. Lesinurad is more potent than probenecid and remains effective even in moderate CKD, in contrast to probenecid. For use, in combination with a xanthine oxidase inhibitor, for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone. Mechanism of action Lesinurad inhibits the activity of uric acid transporter 1 (URAT1) and organic anion transporter 4 (OAT4). Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Allopurinol acts on purine catabolism, without disrupting the ⦠For this reason, oxipurinol is believed responsible for the majority of allopurinol's effect. Wilmington, DE; 2016 Jan. 2. Perez-Ruiz F, Sundy JS, Miner JN et al. Diaz-Torné C, Perez-Herrero N, Perez-Ruiz F. New medications in development for the treatment of hyperuricemia of gout. They increase urate excretion in urine and reduce the concentration in plasma. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout. The mean steady state volume of distribution of lesinurad was approximately 20 L following intravenous dosing. Mechanism of action. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. The metabolism of Lesinurad can be decreased when combined with Abiraterone. Pharmacodynamic, pharmacokinetic and tolerability evaluation of concomitant administration of lesinurad and febuxostat in gout patients with hyperuricaemia. CAS Number: 878672-00-5 Lesinurad is extensively bound to proteins in plasma (greater than 98%), mainly to albumin. 2014; 53:2167-74. http://www.ncbi.nlm.nih.gov/pubmed/24509406?dopt=AbstractPlus, 3. Application number207988Orig1s000: Summary Review. Clin Pharmacol Drug Dev. We comply with the HONcode standard for trustworthy health information -. Mechanism of action In gout, inflammation in joints results from the precipitation of circulating uric acid, exceeding its solubility in blood and depositing as crystals of monosodium urate in and around synovial fluid and soft tissues of joints. Duzallo combines two medications with complementary mechanisms of action. Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Select one or more newsletters to continue. ), Not recommended in patients with normal renal function who are receiving allopurinol dosages <300 mg daily or in patients with estimated Clcr <60 mL/minute who are receiving allopurinol dosages <200 mg daily.1, Not expected to be effective in patients with severe renal impairment; use is contraindicated in such patients.1 (See Renal Impairment under Cautions. URAT1 is a transporter in the kidney that ⦠On the contrary, 7 recent placebo-controlled trials of urate-lowering drugs with different mechanisms of action (uricosuric: lesinurad; xanthine oxidase inhibition: febuxostat; uricase: pegloticase) have observed higher mortality or trends to higher mortality in gout ⦠Urate reabsorbed. Lesinurad undergoes oxidative metabolism mainly via the polymorphic cytochrome P450 CYP2C9 enzyme. Rheumatology (Oxford). Lesinurad is a once-daily, small-molecule, oral inhibitor of SLC22A12 (also known as urate transporter 1 [URAT1]), that is being developed by Ardea Biosciences Lesinurad - AstraZeneca - AdisInsight Either you have JavaScript disabled or your browser does not support Javascript . Brands: Zurampic. Khanna D, Fitzgerald JD, Khanna PP et al. © Copyright 2021, Selected Revisions March 22, 2017. {[5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}acetic acid, Hoy SM: Lesinurad: First Global Approval. Ardea Biosciences is developing lesinurad, an oral, once-daily inhibitor of the urate transporter 1 (URAT1). The molecular mechanism of action of URAT1 inhibitors is unknown. Chemical Name: 2-[[5-bromo-4-(4-cyclopropyl-1-naphthalenyl)-4H-1,2,4-triazol-3-yl]thio]-acetic acid 2012; 64:1431-46. http://www.ncbi.nlm.nih.gov/pubmed/23024028?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3683400&blobtype=pdf, allopurinol, febuxostat, Uloric, Zyloprim, probenecid, allopurinol / lesinurad. Arthritis Res Ther. Lesinurad: First Global Approval. Ann Rheum Dis. Market authorization was granted in February 2016 in Europe and December 2015 in the USA. Data sources include IBM Watson Micromedex (updated 3 Mar 2021), Cerner Multum™ (updated 1 Mar 2021), ASHP (updated 3 Mar 2021) and others. A common misconception is that allopurinol is metabolized by its target, xanthine oxidase, but this action is principally carried out by aldehyde oxidase. Curr Opin Rheumatol. AstraZeneca AB. Acetaminophen may decrease the excretion rate of Lesinurad which could result in a higher serum level. [. 14.1 Overview of Clinical Studies of ZURAMPIC . Undated. Mechanism of Action. Structure of lesinurad (RDEA594), 2- ((5-bromo-4- (4-cyclopropylnaphthalen-1-yl)-4 H -1,2,4-triazol-3-yl)thio) acetic acid In this study, we define the molecular mechanism of action of the uric acid reabsorption inhibitor lesinurad (Zurampic®), previously known as RDEA594. 2012 American College of Rheumatology guidelines for management of gout. Aceclofenac may decrease the excretion rate of Lesinurad which could result in a higher serum level. The metabolism of Acalabrutinib can be increased when combined with Lesinurad. Xanthine and hypoxanthine excretion were reduced by lesinurad. US Food and Drug Administration. Lesinurad is an oral uric acid transporter 1 (URAT1) inhibitor indicated for the treatment of hyperuricemia associated with gout. Lesinurad is used together with other medicines that can cause the body to produce less uric acid. AHFS DI Essentials™. If you believe you are experiencing an interaction, contact a healthcare provider immediately. Urate excreted. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf, 8. Gout occurs as the result of an accumulation of urate crystals in the joints, which cause pain and inflammation. Acemetacin may decrease the excretion rate of Lesinurad which could result in a higher serum level. Arthritis Rheumatol. Drugs. The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout. Xanthine and hypoxanthine excretion were reduced by lesinurad. Lesinurad is used as part of a combination of medicines to treat high levels of uric acid in your blood, also called hyperuricemia (HYE-per-URE-i-SEE-mee-a). Lesinurad (Zurampic) is the first selective uric acid reabsorption inhibitor (SURI) approved by the FDA. Lesinurad helps the kidneys remove uric acid from the body. Class: Uricosuric Agents Fleischmann R, Kerr B, Yeh LT et al. On Aug. 21, the U.S. Food and Drug Administration (FDA) announced the approval of Duzallo (lesinurad and allopurinol) for hyperuricemia associated with gout in patients who have not achieved target serum uric acid (sUA) levels with allopurinol monotherapy. Consistent with its mechanism of action, lesinurad lowered serum uric acid by increasing the amount of urate excreted in urine and the fractional excretion of urate, with the greatest effects observed in the first 6 hours after dosing. ... Nuki G. Colchicine: its mechanism of action and ⦠As a uricosuric agent, a number of precautions should be taken to prevent pathological hyperuricosuria. 5. 2016; 18:214. http://www.ncbi.nlm.nih.gov/pubmed/27716403?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=5048659&blobtype=pdf. The metabolism of Lesinurad can be increased when combined with Abatacept. The metabolism of Acenocoumarol can be decreased when combined with Lesinurad. The metabolism of Abemaciclib can be increased when combined with Lesinurad. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout. Hoy SM. 12.2 Pharmacodynamics . Lesinurad is the most recent drug molecule approved by US FDA & EMA for the treatment of gout in patients with uncontrolled gout along with allopurinol. This information should not be interpreted without the help of a healthcare provider. Allopurinol reduces the production of uric acid (UA); lesinurad increases renal excretion of UA by selectively inhibiting the action of URAT1, the UA transporter responsible for ⦠2016; :. ), Major adverse cardiovascular events (i.e., cardiovascular death, nonfatal MI, nonfatal stroke) reported in clinical studies; causal relationship not established.1, Data not available regarding use in pregnant women.1 Animal studies revealed no evidence of teratogenicity, embryofetal toxicity, or adverse developmental effects.1, Not known whether lesinurad is distributed into human milk or has any effects on breast-fed infants or on milk production.1 Distributed into milk in rats in concentrations approximately equivalent to plasma concentrations.1, Consider the benefits of breast-feeding along with the importance of the drug to the woman and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.1, Safety and efficacy in pediatric patients <18 years of age not established.1, No overall differences in safety and efficacy observed between geriatric patients and younger adults.1 However, possibility of greater sensitivity of some older patients cannot be ruled out.1, Mild or moderate hepatic impairment does not substantially alter lesinurad pharmacokinetics.1 4, Not studied in patients with severe hepatic impairment and not recommended in this population.1, AUC is increased in patients with renal impairment.1 (See Special Populations under Pharmacokinetics: Absorption. Mechanism of action Sulfinpyrazone and lesinurad competitively inhibit the urate anion transporter (URAT1) responsible for reabsorption of uric acid in the proximal tubule. Build effective decision support tools with the industryâs most comprehensive, Easily connect various identifiers back to our datasets, InChI=1S/C17H14BrN3O2S/c18-16-19-20-17(24-9-15(22)23)21(16)14-8-7-11(10-5-6-10)12-3-1-2-4-13(12)14/h1-4,7-8,10H,5-6,9H2,(H,22,23), 2-{[5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}acetic acid, OC(=O)CSC1=NN=C(Br)N1C1=CC=C(C2CC2)C2=C1C=CC=C2, Accelerate your drug discovery research with our ADMET & drug target dataset, Power your clinical software with the most comprehensive allergy info on the market, M04AB — Preparations increasing uric acid excretion, Preparations Increasing Uric Acid Excretion, Predicted MS/MS Spectrum - 10V, Positive (Annotated), Predicted MS/MS Spectrum - 20V, Positive (Annotated), Predicted MS/MS Spectrum - 40V, Positive (Annotated), Predicted MS/MS Spectrum - 10V, Negative (Annotated), Predicted MS/MS Spectrum - 20V, Negative (Annotated), Predicted MS/MS Spectrum - 40V, Negative (Annotated). Acute renal failure reported; more common when lesinurad administered as monotherapy.1 Use lesinurad in combination with a xanthine oxidase inhibitor (e.g., allopurinol, febuxostat).1 (See Renal Effects under Cautions. DUZALLO lowers serum uric acid levels by increasing excretion and inhibiting production of uric acid. It reduces serum uric acid concentration through the inhibition of URAT1, an enzyme responsible for reuptake of uric acid from the renal tubule, and OAT4, another uric acid transporter associated with diuretic-induced hyperuricemia. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000SumR.pdf. Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. 1. Some compounds inhibit URAT1-mediated urate transport in a competitive manner 25 , 26 , ⦠9. URAT1 is a major transporter enzyme responsible for reuptake of uric acid from the renal tubules; inhibition of URAT1 function thereby increases excretion of uric acid. Miner J, Tan PK, Hyndman D et al. 14.2 Add-on to Allopurinol in Inadequate Responders . Areas covered: This review discusses the drugs in preclinical and early clinical trials for hyperuricemia, their mechanisms of action and available results. Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney. Södertälje, Sweden. Most of the radioactivity recovered in urine (> 60% of dose) occurred in the first 24 hours. The active metabolite of allopurinol is oxipurinol, which is also an inhibitor of xanthine oxidase. ), Uricosuric agent; uric acid transporter 1 (URAT1) and organic anion transporter 4 (OAT4) inhibitor.1 2 4 5 6 8, Management of hyperuricemia associated with gout in patients who have not attained target serum uric acid concentrations with xanthine oxidase inhibitor monotherapy; use in combination with a xanthine oxidase inhibitor (e.g., allopurinol, febuxostat).1 10, American College of Rheumatology states that serum urate concentrations in gout patients should be reduced sufficiently to result in durable improvement in signs and symptoms of the disease and recommends a target serum urate concentration of <6 mg/dL (or <5 mg/dL if necessary to achieve such clinical improvements).11, Do not use as monotherapy.1 (See Renal Effects under Cautions. 13 NONCLINICAL TOXICOLOGY . Available for Android and iOS devices. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. The absence of an interaction does not necessarily mean no interactions exist. Lesinurad reduces serum uric acid levels by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney. Trend toward lesser efficacy observed in patients with estimated Clcr <45 mL/minute (only limited experience in this population).1, Efficacy and safety not established in those with severe renal impairment (estimated Clcr <30 mL/minute) or end-stage renal disease, or in those undergoing dialysis; not expected to be effective in these patients.1 Contraindicated in these patients and in renal transplant recipients.1, Assess renal function before initiating lesinurad and periodically thereafter as clinically appropriate; more frequent monitoring recommended in patients with estimated Clcr <60 mL/minute or with increases in Scr to 1.5–2 times the baseline value.1 Do not initiate in patients with estimated Clcr <45 mL/minute; discontinue lesinurad if estimated Clcr is persistently <45 mL/minute.1, Use with caution in patients who are poor CYP2C9 metabolizers; lesinurad exposure may be increased.1 (See Special Populations under Pharmacokinetics: Absorption. Lesinurad plus febuxostat provides dual mechanisms of action to lower urate levels for patients with tophaceous gout. Molecular Formula: C17H14BrN3O2S Allopurinol is almost completely metabolized to oxipurinol within two hours of oral administration, whereas oxipurinol is slowly excreted by the kidneys over 18â30 hours. ), In clinical studies of combination lesinurad and xanthine oxidase inhibitor therapy, 62% of patients had mild or moderate renal impairment.1 No clear differences in safety and efficacy in patients with mild renal impairment (estimated Clcr 60 to <90 mL/minute) compared with those with normal renal function.1 Patients with moderate renal impairment (estimated Clcr 30 to <60 mL/minute) had higher incidence of adverse renal effects compared with those with mild renal impairment or normal renal function.1 (See Renal Effects under Cautions.) [, Gillen M, Yang C, Wilson D, Valdez S, Lee C, Kerr B, Shen Z: Evaluation of Pharmacokinetic Interactions Between Lesinurad, a New Selective Urate Reabsorption Inhibitor, and CYP Enzyme Substrates Sildenafil, Amlodipine, Tolbutamide, and Repaglinide. Lesinurad is a novel addition to the therapeutic armamentarium against gout. Consistent with its mechanism of action, lesinurad lowered serum uric acid by increasing the amount of urate excreted in urine and the fractional excretion of urate, with the greatest effects observed in the first 6 hours after dosing. 2017 Jul;6(4):363-376. doi: 10.1002/cpdd.324. Unchanged lesinurad in urine accounted for approximately 30% of the dose. Application number207988Orig1s000: Clinical Pharmacology and Biopharmaceutics Review(s). Carcinogenesis, Mutagenesis, Impairment of Fertility . Medically reviewed by Drugs.com. Allopurinol is a structural isomer of hypoxanthine.Allopurinol inhibits xanthine oxidase, an enzyme that converts oxypurines to uric acid.By blocking the production of uric acid, this agent decreases serum and urine concentrations of uric acid, thereby providing protection against uric acid-mediated end organ damage in conditions associated with excessive production of uric acid, i.e. Arthritis Care Res (Hoboken). By inhibiting URAT1, lesinurad increases the excretion of uric acid in the kidney and lowers serum UA levels 10, 11. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout. Drug created on March 10, 2016 03:25 / Updated on February 21, 2021 18:53, Accelerate your drug discovery research with our fully connected ADMET dataset, With our commercial data, access important information on, Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects, Reduce medical errors & improve treatment outcomes with our adverse effects data.
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