Oprelvekin

Key takeaways

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

Reference excerpt

Oprelvekin is recombinant interleukin eleven (IL-11), a thrombopoietic growth factor that directly stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation resulting in increased platelet production. It is marketed under the trade name Neumega.

Chemical, pharmacological and marketing data IL-11 is a member of a family of human growth factors and is being produced in the bone marrow of healthy adults. Synonyms are:

AGIF Adipogenesis inhibitory factor Interleukin-11 precursor. Oprelvekin is produced in Escherichia coli (E. coli) by recombinant DNA technology. The protein has a molecular mass of approximately 19,000 g/mol, and is non-glycosylated. The polypeptide is 177 amino acids in length (the natural IL-11 has 178). This alteration has not resulted in measurable differences in bioactivity either in vitro or in vivo. The primary hematopoietic activity of Neumega is stimulation of megakaryocytopoiesis and thrombopoiesis. In mice and nonhuman primate studies Neumega has shown potent thrombopoietic activity in compromised hematopoiesis, including moderately to severely myelosuppressed animals. In these studies, Neumega improved platelet nadirs and accelerated platelet recoveries compared to controls. In animal studies oprelvekin also has non-hematopoietic activities. This includes the regulation of intestinal epithelium growth (enhanced healing of gastrointestinal lesions), the inhibition of adipogenesis, the induction of acute phase protein synthesis (e.g., fibrinogen), and inhibition of macrophageal released pro-inflammatory cytokines. However, pathologic changes, some also seen in humans, have been noticed:

papilledema fibrosis of tendons and joint capsules periosteal thickening and embryotoxicity (see under pregnancy). In preclinical human trials mature megakaryocytes which develop during in vivo treatment with Neumega were ultrastructurally, morphologically, and functionally normal. They also showed a normal life span. In a study in which a single 50 μg/kg subcutaneous dose was administered to eighteen healthy men, the peak serum concentration (Cmax) of 17.4 ± 5.4 ng/mL was reached at 3.2 ± 2.4 h (Tmax) following dosing. The terminal half-life was 6.9 ± 1.7 hours. In a second study in which single 75 μg/kg subcutaneous and intravenous doses were administered to twenty-four healthy subjects, the pharmacokinetic profiles were similar between men and women. The absolute bioavailability of Neumega was >80%. In a study in which multiple, subcutaneous doses of both 25 and 50 μg/kg were administered to cancer patients receiving chemotherapy, Neumega did not accumulate and clearance of Neumega was not altered following multiple doses. Pediatric cancer patients treated with aggressive chemotherapy showed similar pharmakinetic characteristics. In humans treated with oprelvekin on a daily base a twofold increase in fibrinogen levels occurred. Healthy volunteers displayed an increase in von-Willebrand-factor (vWf) activity. Isolated molecules formed under oprelvekin were found to have exact the same multimere structure as the 'normal' factor and were therefore fully functioning. These increases in coagulation factors may contribute to the development of stroke (see under § Side effects), but a precise association cannot be made at this stage. In a variety of clinical studies upon which FDA approval is based, Neumega showed effectivity in reducing thrombocytopenia in oncologic patients treated with myelosuppressant chemotherapeutic drugs as measured by significantly decreased need of platelet transfusions. Neumega is manufactured and sold by Wyeth. The drug is formulated in single-use vials containing 5 mg of oprelvekin (specific activity approximately 8 million units/mg) as a sterile, lyophilized powder. The FDA approved the drug in 1997.

Indications Neumega is indicated for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in adult patients with nonmyeloid malignancies who are at high risk of severe thrombocytopenia. Efficacy was demonstrated in patients who had experienced severe thrombocytopenia following the previous chemotherapy cycle.

Contraindications and precautions Patients with known hypersensitivity to Oprelvekin itself or any other ingredient. Patients with severe or decompensated heart failure should not be treated, because Oprelvekin may cause excessive fluid retention with edema and cardiac decompensation. Patients with compensated heart disease should be treated with caution and under permanent clinical supervision. Neumega is not indicated following myeloablative chemotherapy (increased likelihood of severe side-effects) and in pediatric patients. Renal impairment: Neumega is excreted renally. No differences of pharmakinetic parameters and clinical differences have been seen in mild to moderate impairment. Severe impairment has led to an increased number of patients with reduced hemoglobin due to dilutional anemia. Patients with severely disturbed renal function should be monitored very closely. The efficacy of Oprelvekin has not been systematically studied in patients receiving chemotherapy regimes of more than 5 days duration/each cycle or in those regimes containing agents that induce delayed thrombocytopenia (e.g. nitrosoureas, mitomycin C. Neumega should not be given in these cases.

Pregnancy In studies with rats and rabbits treated chronically, Oprelvekin showed embryo- and fetotoxicity (early death of embryos and reduction of number of fetus, fetal malformations etc.). There is no sufficient human data available. Pregnant women should only be treated, if the benefit to the mother outweighs the potential risk to the unborn.

Lactation No human data is available if the drug is distributed into human milk. Nursing women should either discontinue breast-feeding or Neumega, the decision should take into account the importance of the drug to the mother.

… excerpt ends here. Continue reading the full article.

Worked examples

Example 1 — a first encounter with Oprelvekin

Start with the simplest possible case. Write down what Oprelvekin claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, 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 Oprelvekin 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 Oprelvekin 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 Oprelvekin

In research: Oprelvekin appears in science 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 Oprelvekin 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: Oprelvekin is common in secondary-school and first-year university syllabi. It links to neighbouring topics Cytokines, Drugs developed by Pfizer, Embryotoxicants, so understanding it makes those chapters shorter.
In everyday life: Look for Oprelvekin 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.

How to study Oprelvekin in 20 minutes

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

Frequently asked questions

What is Oprelvekin in simple terms?

Oprelvekin is recombinant interleukin eleven (IL-11), a thrombopoietic growth factor that directly stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation resulting in increased platelet production. It is marketed under the tr…

Why does Oprelvekin matter?

Because it connects several science 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 Oprelvekin?

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 Oprelvekin.