Scientistsat Gilead discovered the Oseltamivir by use shikimic acid as thebeginning point for synthesis. Previously, shikimic acid wasextracted from Chinese star anise, but since 2006, pharmaceuticalsmanufacture the shikimic acid recombinantly in E. coli (Ward,Small, Smith, Suter, & Dutkowski, 2015).Roche got the license and relevant patents from Gilead to produce in 1996. In the same year, oseltamivir phosphate was approvedFDA for the treatment of flu in adults after two double-blinded,placebo-controlled, and randomized clinical trials. This work willreview the properties of the drug, the uses, and how the drugs work.
is produced through asymmetric syntheses from the chiral naturalmaterial which act enantiomers since they are readily available andcheap. Oseltamivir has three chiral centers close to each other.Hence, the desirable natural product for oseltamivir must have threechiral centers close to each other like the Shikimic acid
Figure1: Comparison between Shikimic acid and Oseltamivir
Theacid also has a carboxylic group that can be converted into ester inthe target structure (Appendix 1 and 2). The molecular formula of is C16H31N2O8P, and the chemical structure is illustratedbelow:
Figure2: Molecular structure of Oseltamivir
Oseltamivirphosphate is a neuraminidase inhibitor which is considered as anactive component of . The structure is realized by a singlecrystal X-ray diffraction having synchrotron radiation. Additionally,the structure reproduces by fusing to the inhibitor in theneuraminidase active site and offers appropriate structuralparameters and a thorough insight into the inhibitor’s bindingpreferences (Magano,2012).
Usesof or Oseltamivir Phosphate
or oseltamivir phosphate is antiviral drug administered orally whichhas been approved by FDA to treat acute, uncomplicated influenzaamong patients aged over two weeks old and above. Specifically, whileusing the drug the patient’s symptoms should not have lasted formore than two days (Roberts,Gantt, Paquette, & Kang, 2016).The flu symptoms include body aches, stuffy or a runny nose, fever,cough, chills, headache, and fatigue. Nonetheless, the prevention offlu has not been established among patients who are immunocompromised(Ward,et al, 2015).The antiviral drugs cannot be considered as an alternative to gettinga flu vaccine. Nonetheless, a flu vaccine is the surest bet to stopseasonal influenza. The antiviral drugs are considered as the secondline of defense to treat influenza inclusive of both variant flu, andseasonal flu viruses is a person gets sick.
Despitegetting a flu shot or vaccine, a person is not necessary immuneespecially among seniors, pregnant women, small children, andpatients suffering from respiratory and cardiac diseases (Robertset al., 2016).Influenza can lead to pneumonia. The antiviral medication wasapproved in 1999 works by stopping infected cells from bursting thenreleasing the flu virus which infects the adjoining cells. Theprocess can be mitigated within forty-eight hours after the firstsymptoms. Roche the company that manufactures asserts thatthe medicine reduces the frequency of bacterial infections likepneumonia. Some the related side effects that must be monitoredinclude vomiting, nausea, abnormal behavior, and delirium. Other sideeffects include stuffy nose, runny nose, diarrhea, and cough (Magano,2012).
Asprescriptions drugs, they reduce the capacity of the flu viruses toreproduce. Doctors can recommend the drug when a person closelycontacts another person suffering from the flu. Nonetheless, thepreventative use of the drug is discouraged by CDC since it can leadto drug-resistant strains of the flu virus. As an antiviral drug, is usually not sold over-the-counter, but they are prescribedby a health care provider or a doctor. Furthermore, the antiviral areusually different from the antibiotics which mostly fight thebacterial infections.
is packed or available as a 75mg, 45mg, or 30mg oseltamivir phosphatecapsule as well as powder for oral suspension which when dissolved inwater as prescribed has 12 mg/mL oseltamivir base (Magano,2012).In most cases, oseltamivir is prescribed for five days nonetheless,a person who is hospitalized with influenza might need the medicinefor more than five days (Robertset al., 2016).For pregnant women, there are prescribed the oral oseltamivir sinceit is considered as beneficial and safe.
Howthe Drug Works
Oseltamiviris known as neuraminidase inhibitor mostly a competitive inhibitor ofthe neuraminidase enzyme of influenza. The enzyme slivers the sialicacid contained on the glycoproteins on human cells’ surface as wellas it assist new virions to depart them. Therefore, the oseltamivirstops the release of new viral particles.
’soral bioavailability is more than 80 percent, and it is widelymetabolized to its active form after passing via the liver. TheOseltamivir contains a distribution volume of 23 to 26 liters.Besides, the drug half-life is nearly one to three hours (Robertset al., 2016).’s active carboxylate metabolite half-life is nearly six toten hours with nearly ninety percent of the oral dose being removedfrom the body through urine as the active metabolite.
Theresistance to is largely caused by mutations of the singleamino acid residue substitutions in the neuraminidase enzyme.Influenza A virus mostly sequesters with low exposure to oseltamivircarboxylate have been recovered by sequential passage of virus incell culture in the presence of accumulating oseltamivircarboxylate’s concentration (Robertset al., 2016).Genetic analysis of such isolates proved that the low exposure tooseltamivir carboxylate is related to the mutation that leads toamino acid variations in the viral hemagglutinin or viralneuraminidase or both. Additionally, oseltamivir-resistant mayperhaps be considerably be related to pneumonia (Ward,et al, 2015). Such patients have a lengthy shedding of oseltamivir-resistant virusdespite withdrawing oseltamivir treatment. Additionally, the H1N1 fluor "Swine flu" patients have also demonstrated considerableresistance to oseltamivir. Additionally, such resistance has beenprevalent in seasonal flu (Magano,2012).Studies done have also proved that people suffering from H3N2 havehigh levels of resistance.
or oseltamivir phosphate is antiviral drug administered orally whichhas been approved by FDA to treat acute, uncomplicated influenzaamong patients aged over two weeks old and above. As a prescriptionsdrug, they reduce the capacity of the flu viruses to reproduce. It isalso produced from Shikimicacid. Theoseltamivir stops the release of new viral particles. Knownresistance to is largely caused by mutations of the singleamino acid residue substitutions in the neuraminidase enzyme
Magano,J. (2012). Synthetic approaches to the neuraminidase inhibitorszanamivir (Relenza) and oseltamivir phosphate () for thetreatment of influenza. Chemicalreviews, 109(9),4398-4438.
Roberts,A., Gantt, S., Ng, K., Paquette, V., & Kang, K. (2016). Re:Management of influenza with Reply. BritishColumbia Medical Journal, 58(1),7-7.
Ward,P., Small, I., Smith, J., Suter, P., & Dutkowski, R. (2015).Oseltamivir (®) and its potential for use in the event of aninfluenza pandemic. Journalof Antimicrobial Chemotherapy, 55(Suppl1), i5-i21.
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