It is a genetically engineered analogue of hGH conjugated
with PEG which was approved for use in 2003 . Acromegaly is a chronic metabolic disorder caused when the pituitary gland generates excess hGH after epiphyseal plate closure. GH receptor has two binding sites: (i) binds to site 1 and (ii) then to site 2, inducing the functional dimerization of the hGH receptor. Pegvisomant inhibits the dimerization of the hGH receptor due to its increased affinity for site 1 of the hGH receptor . With eight amino acid mutations at the site, and by the substitution of position 120 glycine to arginine, inhibits hGH receptor dimerization. Overall, PEGylation reduces the activity of the GH receptor antagonist. #Ixazomib cost keyword# However, the 4–6 PEG-5000 moieties added to pegvisomant prolongs its half-life and allow once-daily administration immunogenicity as the rate of clearance from the body are greatly reduced, making it an effective drug against acromegaly . The recommended dosage for patients begins with subcutaneous administration of 40mg dose. The patient can self-administer 10mg
of Somavert daily with adjustments Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical to the dosage of Somavert in 5mg increments depending on the elevation or decline of insulin growth factor-1 (IGF-I) levels [91, 92]. However, because pegvisomant can increase glucose tolerance, care is embarked for the diabetes mellitus patients . 6.1.7. Neulasta (Pegfilgrastim) Amgen’s pegfilgrastim (Neulasta) is developed using filgrastim (Neupogen, Amgen) from Nektar (formerly Shearwater) PEGylation technology. The conjugate is formed by conjugating Inhibitors,research,lifescience,medical a 20kDa linear monomethoxy-PEG aldehyde with Granulocyte-Colony Stimulating Factor G-CSF . Neulasta is used to decrease febrile neutropenia manifested infection and was approved for Inhibitors,research,lifescience,medical use in 2002. The PEGylation
increases the protein serum half-life to 42h compared to the serum half-life of 3.5–3.8h for the unmodified G-CSF. Therefore, the overall dose is reduced to a single cycle dose that is as effective as daily doses of native G-CSF [94–96]. The recommended dose of Neulasta is a single administration of 6mg subcutaneously once-per-chemotherapy cycle and advised of not delivering it within 14 days before and 24 days after administration of chemotherapeutics . 6.1.8. Krystexxa (Pegloticase) Krystexxa (pegloticase) by Savient, a PEGylated mammalian urate oxidase (uricase) was FDA approved in 2010 . It is a recombinant tetrameric urate oxidase used for the treatment of chronic gout. because Pegloticase acts by preventing inflammation and pain due to urate crystal formation in plasma. The advantage of pegloticase over other standard treatments is the higher effectiveness in reducing gout tophi . However, pegloticase has been reported to be immunogenic. Subcutaneous and intravenous injections of pegloticase in clinical trials showed production of antibodies [100–102]. However, it was found out that the antibodies produced were due to PEG and not because of uricase.