Zurampic Case Study

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The development of Zurampic®(Lesinurad), a first selective uric acid resorption inhibitor to treat gout
Summary: Gout is the most common inflammatory arthropathy in the western world, which is caused by the excess accumulation of uric acid in the blood instead of normally excreting by kidney. Millions of people suffer from this kind of arthritis with an attack of sudden burning pain, stiffness, and swelling in a joint(usually a big toe). However, the current treatment for gout is far from adequate, because controlling the acute episode has been the prior management for decades by using nonsteroidal antinflammatory drugs (NSAIDs), colchicine or glucocorticoids. With a deeper understanding of gout pathophysiology these years, urate lowing has
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Renal-related adverse reactions and cardiovascular events are the most common adverse effects when a patient is prescribed with Zurampic. Since the basic mechanism of Zurampic is to reduce the absorption of uric acid by inhibiting the activity of URAT1 transporter, the increase of renal uric acid excretion would lead to the transient increase in serum creatinine, which is widely used as an indicator to estimate the renal function index, glomerular filtration rate (GFR).[14] Thus, test the serum creatinine level in the clinical trial would help evaluate whether renal function would be affected after taking Zurampic in combination with the xanthine oxidase inhibitor(XOI) comparing with XOI alone. The result(shown as Table 1) has shown that the increased serum creatinine level side effects occurred more frequently(10.0%) in patients receiving 400 mg Zurampic in combination with XOI than 3.9% frequency in patients receiving 200 mg Zurampic in combination with XOI.[9] Moreover, the result did show that the treatment of Zurampic would elevate the baseline of creatinine level in blood comparing with the frequency(2.3%)in placebo group. Except for the serum creatintine level, the frequency of renal failure side effects(including acute or chronic renal failure, renal impairment, …show more content…
Since the transporters expressed in the kidney and liver play an important role in the process of inhibiting urate absorption, a phase I study was conducted to evaluate the drug-drug interaction between Zurampic(lesinurad) and atorvastatin, metformin, or furosemide(substrates of major liver or kidney transporters) in clinical studies by recruiting only healthy male subjects(ages 18–65 years; body mass index 18–32 kg/m2). 28 subjects received 40 mg atorvastatin with or without 200 mg or 400 mg lesinurad; 12 subjects received 850 mg metformin with or without 400 mg lesinurad; 11 subjects received 40 mg furosemide with or without 400 mg lesinurad.[15] The result has shown that there is not a statistically drug and drug interaction between lesinurad and substrates of major liver or kidney transporters(atrovastatin, metformin, furosemide), even though the treatment with lesinurad(200 mg or 400 mg)would alter the maximum concentration(Cmax)and area under the concentration–time curve (AUC) of atrovastatin and furosemide, lesinurad would not change the renal clearance and diuretic activity of these drugs.[15] However, lesinurad definitely has some interaction with drugs of CYP2C9 inhibitors(such as fluconazole) or inducers(such as rifampin), which would influence the metabolic process of lesinurad. Besides the class of CYP2C9, the

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