chemistry

Nintedanib

Nintedanib 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 Nintedanib rather than just read about it. In short: Nintedanib, sold under the brand names Ofev and Vargatef, is an oral medication used for the treatment of idiopathic pulmonary fibrosis and along with other medications for some types of non-small-cell lung cancer. In March 2020, it was approved for use in the United States to treat chronic fibrosing (scarring) interstitial lung diseases (ILD) with a progressive phenotype (trait).

Key takeaways

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

Reference excerpt

Nintedanib, sold under the brand names Ofev and Vargatef, is an oral medication used for the treatment of idiopathic pulmonary fibrosis and along with other medications for some types of non-small-cell lung cancer. In March 2020, it was approved for use in the United States to treat chronic fibrosing (scarring) interstitial lung diseases (ILD) with a progressive phenotype (trait). It is the first treatment for this group of fibrosing lung diseases that worsen over time that was approved by the U.S. Food and Drug Administration (FDA). Common side effects include abdominal pain, vomiting, and diarrhea. It is a small molecule tyrosine-kinase inhibitor, targeting vascular endothelial growth factor receptor, fibroblast growth factor receptor and platelet derived growth factor receptor. Ofev was developed by Boehringer Ingelheim. It received U.S. Food and Drug Administration (FDA) approval for use for idiopathic pulmonary fibrosis in 2014 – one of only two drugs available for treating IPF – and numerous studies since have demonstrated its effectiveness in slowing the progressive, terminal lung disease.

Medical uses

Idiopathic pulmonary fibrosis Nintedanib is used for the treatment of idiopathic pulmonary fibrosis. It has been shown to slow down decrease in forced vital capacity, and it also improves people's quality of life. Nintedanib does not improve survival in people with IPF. It interferes with processes like fibroblast proliferation, differentiation and laying down extracellular matrix. The National Institute for Health and Care Excellence (NICE) recommends nintedanib in cases of IPF where the FVC is 50-80% of predicted. NICE recommends discontinuation of therapy if a person's FVC decreases by 10% or more in a 12-month period, indicating disease progression despite treatment.

Lung cancer It is also used in combination with docetaxel as a second-line treatment for adult patients with locally advanced, metastatic, or locally recurring non-small cell lung cancer of adenocarcinoma histology. It is unclear how this combination compares to other second line agents as the comparisons have not been done as of 2014.

Contraindications Nintedanib is contraindicated in patients with known hypersensitivity to nintedanib, peanut or soya. Nintedanib has not been tested in patients with moderate to severe impairment of liver function. Given that the drug is metabolised in the liver, it may not be safe in such patients. Nintedanib can be used in geriatric population without any dose modifications. It has not been studied in paediatric populations and hence cannot be given in patients below 18 years of age. It is also contraindicated in pregnancy.

Adverse effects Common side effects noted with nintedanib include anorexia, nausea, vomiting, diarrhea, abdominal pain, gastrointestinal perforation, weight loss, arterial thromboembolism (including myocardial infarction), bleeding, hypothyroidism, elevated liver enzymes, and headache. Gastrointestinal side effects are decreased when nintedanib is co-administered with food. Side effects observed with nintedanib were worse with a higher dose. For this reason, subsequent trials have used an equally clinically effective lower dose.

Pharmacology

Mechanism of action Nintedanib competitively inhibits both nonreceptor tyrosine kinases (nRTKs) and receptor tyrosine kinases (RTKs). NRTK targets of nintedanib include Lck, Lyn, and Src. RTK targets of nintedanib include platelet-derived growth factor receptor (PDGFR) α and β; fibroblast growth factor receptor (FGFR) 1, 2, and 3; vascular endothelial growth factor receptor (VEGFR) 1, 2, and 3; and FLT3. Its use in IPF is predicated on its inhibition of PDGFR, FGFR, and VEGFR, which increase fibroblast proliferation, migration, and transformation.

Pharmacokinetics

Only a small percentage of orally taken nintedanib is absorbed in the gut, partially due to transport proteins (such as P-glycoprotein) moving the substance back into the lumen. Combined with a high first-pass effect, this results in an oral bioavailability of about 4.7% with a 100 mg tablet. The drug reaches peak plasma levels in 2 to 4 hours after oral intake in the form of a soft gelatin capsule. Nintedanib is mainly inactivated by esterases that cleave the methyl ester, resulting in the free carboxylic acid form, which is then glucuronidated by uridinediphosphate-glucuronosyltransferases and excreted mostly via the bile and faeces. No relevant cytochrome P450 mediated metabolism has been observed. Western blot showed Nintedanib has sustained inhibition on receptor phosphorylation for at least 32 hours.

Interactions Nintedanib is a substrate of the transporter P-glycoprotein which moves the absorbed substance back into the gut's lumen. The P-glycoprotein inhibitor ketoconazole is known to increase blood plasma levels of nintedanib by a factor of 1.8; other inhibitors such as erythromycin or ciclosporin are expected to have a similar effect. On the other hand, the P-glycoprotein inducer rifampicin cuts nintedanib plasma levels in half; other inducers such as carbamazepine, phenytoin or St. John's Wort probably lower plasma levels as well.

Chemistry

The drug is used in form of its salt with ethanesulfonic acid. This salt, nintedanib esilate, is a yellow, crystalline solid that melts at 244 °C (471 °F) to 251 °C (484 °F). It has poor solubility in water, and somewhat better solubility in dimethyl sulfoxide at 25 g/L.

History

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Nintedanib

Start with the simplest possible case. Write down what Nintedanib 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 Nintedanib 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 Nintedanib 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 Nintedanib

In research: Nintedanib 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 Nintedanib 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: Nintedanib is common in secondary-school and first-year university syllabi. It links to neighbouring topics 4-Methylpiperazin-1-yl compounds, Drugs developed by Boehringer Ingelheim, Methyl esters, so understanding it makes those chapters shorter.
In everyday life: Look for Nintedanib 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 Nintedanib in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Nintedanib 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 Nintedanib out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Nintedanib in simple terms?

Why does Nintedanib 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 Nintedanib?

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 Nintedanib.