chemistry

Lesinurad

Lesinurad is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Lesinurad rather than just read about it. In short: Lesinurad (brand name Zurampic) is a uricosuric and urate transporter inhibitor for treating high blood uric acid levels associated with gout. It is recommended only as an adjuvant with either allopurinol or febuxostat when these medications are not sufficient.

Key takeaways

Lesinurad belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Lesinurad to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Lesinurad from memory before moving on to harder problems.

Reference excerpt

Lesinurad (brand name Zurampic) is a uricosuric and urate transporter inhibitor for treating high blood uric acid levels associated with gout. It is recommended only as an adjuvant with either allopurinol or febuxostat when these medications are not sufficient. It received FDA approval on 22 December 2015. The European Commission granted a marketing authorisation valid throughout the European Union on 18 February 2016. In February 2019, lesinurad was discontinued in the United States by its manufacturer for business reasons, and was subsequently withdrawn in Europe in July 2020.

Medical uses Lesinurad is used in combination with a xanthine oxidase inhibitor, such as allopurinol or febuxostat, for treating hyperuricemia (high levels of uric acid in the blood serum) associated with gout. It is approved only for patients who have not achieved target uric acid levels with a xanthine oxidase inhibitor alone.

Contraindications The drug is contraindicated in people with tumour lysis syndrome or Lesch–Nyhan syndrome (juvenile gout), as well as severe impairment of kidney function, including kidney transplant and hemodialysis patients.

Adverse drug reactions In clinical trials, serum creatinine (an important marker for kidney function) was elevated in 4.3 to 7.8% of patients depending on the dose, as compared to 2.3% under placebo. Manifest kidney problems were less frequent under the standard dose than under placebo: Kidney failure occurred in 2.1% of placebo patients, in 1.2% of patients with the therapeutic standard dose, and in 3.5% of patients with the double dose. For kidney stones, the frequencies were 1.7%, 0.6% and 2.5%, respectively. Other common side effects were influenza (5.1% vs. 2.7% under placebo), headache (5.3% vs. 4.1%), and gastroesophageal reflux disease (2.7% vs. 0.8%). Hypersensitivity reactions were rare (<0.1%).

Interactions The substance is a mild inducer of the liver enzyme CYP3A4. Some drugs that are metabolized by this enzyme have been shown to be slightly less effective when combined with lesinurad, examples including simvastatin and warfarin. It might also be a mild inducer of CYP2B6. On the other hand, lesinurad concentrations in the blood are decreased by drugs that induce CYP2C9 and increased by substances that inhibit this enzyme (such as fluconazole), as well as in people who have genetically determined low CYP2C9 activity. The same may be true of microsomal epoxide hydrolase inhibitors (such as valproic acid). High dose aspirin and related drugs reduce the effectiveness of other anti-gout medications. It is not known conclusively whether this also applies to lesinurad, but low dose aspirin does not negatively affect its activity.

Pharmacology

Mechanism of action Lesinurad inhibits URAT1, a protein that is responsible for reabsorption of uric acid in the kidneys. This leads to increased uric acid excretion with the urine, and consequently lower blood levels. It also inhibits the protein OAT4, which is associated with hyperuricemia caused by diuretic drugs.

Pharmacokinetics

Lesinurad is quickly and practically completely absorbed from the gut. Highest blood plasma concentrations are reached after one to four hours. When in the bloodstream, the substance is almost completely (>98%) bound to plasma proteins, mainly albumin. It is metabolized mainly by the liver enzyme CYP2C9 to various oxidation products, predominantly to a hydroxylated substance called M3 and an epoxide, M3c. The latter is quickly hydrolyzed to the diol M4 by microsomal epoxide hydrolase (mEH). The enzymes CYP1A1, CYP2C19 and CYP3A only play minor roles in its metabolization. Glucuronidation by the enzymes UGT1A1 and UGT2B7 has also been detected. Lesinurad is excreted via the urine (63%) and feces (32%), with a biological half-life of about five hours. Of the excreted dose, 30% are unchanged lesinurad, and the rest are metabolites.

Pharmacogenomics People who are CYP2C9 poor metabolizers are exposed to lesinurad concentrations that are about 1.8-fold higher than those with a normal function of this enzyme.

Chemistry

Lesinurad is a white to off-white powder and is not hygroscopic. It is a 1:1 racemic mixture of atropisomers.

See also Lesinurad/allopurinol, a fixed-dose combination drug

References

Illustrations

Worked examples

Example 1 — a first encounter with Lesinurad

Start with the simplest possible case. Write down what Lesinurad claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Lesinurad before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Lesinurad ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Lesinurad

In research: Lesinurad appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Lesinurad in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Lesinurad is common in secondary-school and first-year university syllabi. It links to neighbouring topics Antigout agents, Atropisomers, Bromoarenes, so understanding it makes those chapters shorter.
In everyday life: Look for Lesinurad outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Lesinurad in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Lesinurad means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Lesinurad out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Lesinurad in simple terms?

Why does Lesinurad matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Lesinurad?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Lesinurad.