chemistry

Rolapitant

Rolapitant 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 Rolapitant rather than just read about it. In short: Rolapitant (INN, trade name Varubi və-ROO-bee in the US and Varuby in the European Union) is a drug originally developed by Schering-Plough and licensed for clinical development by Tesaro, which acts as a selective NK1 receptor antagonist (antagonist for the NK1 receptor). It has been approved as a medication for the treatment of chemotherapy-induced nausea and vomiting (CINV) after clinical trials showed it to have…

Key takeaways

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

Reference excerpt

Rolapitant (INN, trade name Varubi və-ROO-bee in the US and Varuby in the European Union) is a drug originally developed by Schering-Plough and licensed for clinical development by Tesaro, which acts as a selective NK1 receptor antagonist (antagonist for the NK1 receptor). It has been approved as a medication for the treatment of chemotherapy-induced nausea and vomiting (CINV) after clinical trials showed it to have similar or improved efficacy and some improvement in safety over existing drugs for this application.

Medical uses Rolapitant is used in combination with other antiemetic (anti-vomiting) agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. The approved antiemetic combination consists of rolapitant plus dexamethasone and a 5-HT3 antagonist.

Contraindications Under the US approval, rolapitant is contraindicated in combination with thioridazine, whose inactivation could be inhibited by rolapitant. Under the European approval, it is contraindicated in combination with St. John's Wort, which is expected to accelerate inactivation of rolapitant.

Side effects In studies comparing chemotherapy plus rolapitant, dexamethasone and a 5-HT3 antagonist to chemotherapy plus placebo, dexamethasone and a 5-HT3 antagonist, most side effects had comparable frequencies in both groups, and differed more between chemotherapy regimens than between rolapitant and placebo groups. Common side effects included decreased appetite (9% under rolapitant vs. 7% under placebo), neutropenia (9% vs. 8% or 7% vs. 6%, depending on the kind of chemotherapy), dizziness (6% vs. 4%), indigestion and stomatitis (both 4% vs. 2%).

Overdose Up to eightfold therapeutic doses have been given in studies without problems.

Interactions Rolapitant moderately inhibits the liver enzyme CYP2D6. Blood plasma concentrations of the CYP2D6 substrate dextromethorphan have increased threefold when combined with rolapitant; and increased concentrations of other substrates are expected. The drug also inhibits the transporter proteins ABCG2 (breast cancer resistance protein, BCRP) and P-glycoprotein (P-gp), which has been shown to increase plasma concentrations of the ABCG2 substrate sulfasalazine twofold and the P-gp substrate digoxin by 70%. Strong inducers of the liver enzyme CYP3A4 decrease the area under the curve of rolapitant and its active metabolite (called M19); for rifampicin, this effect was almost 90% in a study. Inhibitors of CYP3A4 have no relevant effect on rolapitant concentrations.

Pharmacology

Pharmacodynamics Both rolapitant and its active metabolite M19 block the NK1 receptor with high affinity and selectivity: to block the closely related receptor NK2 or any other of 115 tested receptors and enzymes, more than 1000-fold therapeutic concentrations are necessary.

Pharmacokinetics

Rolapitant is practically completely absorbed from the gut, independently of food intake. It undergoes no measurable first-pass effect in the liver. Highest blood plasma concentrations are reached after about four hours. When in the bloodstream, 99.8% of the substance are bound to plasma proteins. It is metabolized by the liver enzyme CYP3A4, resulting in the major active metabolite M19 (C4-pyrrolidine-hydroxylated rolapitant) and a number of inactive metabolites. Rolapitant is mainly excreted via the feces (52–89%) in unchanged form, and to a lesser extent via the urine (9–20%) in form of its inactive metabolites. Elimination half-life is about seven days (169 to 183 hours) over a wide dosing range.

Chemistry The drug is used in form of rolapitant hydrochloride monohydrate, a white to off-white, slightly hygroscopic crystalline powder. Its maximum solubility in aqueous solutions is at pH 2–4.

References

External links "Rolapitant Injection: MedlinePlus Drug Information". MedlinePlus. 20 August 2020.

Illustrations

Worked examples

Example 1 — a first encounter with Rolapitant

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

In research: Rolapitant 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 Rolapitant 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: Rolapitant is common in secondary-school and first-year university syllabi. It links to neighbouring topics 3,5-bis(Trifluoromethyl)phenyl compounds, Antiemetics, CYP2D6 inhibitors, so understanding it makes those chapters shorter.
In everyday life: Look for Rolapitant 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 Rolapitant in 20 minutes

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

Frequently asked questions

What is Rolapitant in simple terms?

Why does Rolapitant 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 Rolapitant?

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 Rolapitant.