Oprelvekin
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| AHFS/Drugs.com | Monograph |
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| Routes of administration |
s.c. injection |
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| Pharmacokinetic data | |
| Bioavailability | >80% (s.c. application) |
| Metabolism | mainly renal |
| Biological half-life | 6.9 ± 1.7h |
| Identifiers | |
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| Chemical and physical data | |
| Formula | C854H1411N253O235S2 |
| Molar mass | approx. 19,000 g/mol |
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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.
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:
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-hematopoetic 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:
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 h. 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.
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