Oseltamivir is an antiviral drug used in the treatment and prophylaxis of both influenza virus A and influenza virus B. It was approved for seasonal influenza by US Food and Drug Administration in 1999, and approval from Japanese agencies and European Medicines Agency (EMA) followed soon afterwards.
A pharmaceutical company Roche launched oseltamivir in the global market with Tamiflu as its brand name. In 2007 alone this pharmaceutical company was producing 400 million doses of the drug with a market value of 2.2 billion US dollars, and benefitted by more than 18 billion US dollars since the launch of the drug.
Synthesis from shikimic acid
In the pharmaceutical industry, shikimic acid (3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid) …show more content…
Fermentative production of shikimic acid is most successfully carried out by rationally designed strains of Escherichia coli by blocking the aromatic amino acid pathway after the production of shikimic acid.
An alternative way is to produce shikimic acid as a result of dephosphorylation of shikimate-3-phosphate. Engineering the uptake of carbon, central metabolism, the regulatory circuits and the common aromatic pathway (including shikimic acid import) have all been targeted to effect higher productivities and lower by-product formation.
Biotransformation of quinic acid can also be pursued as an alternative microbial route. Certain microorganisms (such as Aspergillus, Achromobacter and Pseudomonas) can use quinic acid as the sole carbon source to produce aromatic amino acids via the shikimic acid pathway. Strains of Escherichia coli specifically engineered for overproducing quinic acid from glucose have also been …show more content…
For example, a novel synthesis route has been recently published that obviates raw materials and uses monotrimethylsilyl-acetylene (TMSA) on the easily accessible component 1,4-cyclohexadiene.
Formulations of oseltamivir
Oseltamivir is available in capsules with three dosage options (30, 45, and 75 mg), powder for oral suspension, and in intravenous form (predominately for clinical trials). Both 75 mg capsules and powder formulation have been shown to be bioequivalent dosage forms, and can be stockpiled for use in a pandemic situation.
The capsules can be used for both treatment and prophylaxis in adolescent and adult patients. The powder formulation is primarily intended to enable children to receive the drug, but may also be used by adults who are unable to swallow capsules. Oseltamivir capsules have a shelf life of 5 years, powder formulation 24 months, and reconstituted solution 10 days (if stored at 2 to 8 °C).
Oseltamivir is available to governments in magistral formulation. The active pharmaceutical ingredient is a water-soluble dry powder, with a very long shelf-life when stored in sealed drums. When dissolved in water (15 mg/mL) the solution is stable for three weeks if stored not above 25 °C, and for 6 weeks at 5
A pharmaceutical company Roche launched oseltamivir in the global market with Tamiflu as its brand name. In 2007 alone this pharmaceutical company was producing 400 million doses of the drug with a market value of 2.2 billion US dollars, and benefitted by more than 18 billion US dollars since the launch of the drug.
Synthesis from shikimic acid
In the pharmaceutical industry, shikimic acid (3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid) …show more content…
Fermentative production of shikimic acid is most successfully carried out by rationally designed strains of Escherichia coli by blocking the aromatic amino acid pathway after the production of shikimic acid.
An alternative way is to produce shikimic acid as a result of dephosphorylation of shikimate-3-phosphate. Engineering the uptake of carbon, central metabolism, the regulatory circuits and the common aromatic pathway (including shikimic acid import) have all been targeted to effect higher productivities and lower by-product formation.
Biotransformation of quinic acid can also be pursued as an alternative microbial route. Certain microorganisms (such as Aspergillus, Achromobacter and Pseudomonas) can use quinic acid as the sole carbon source to produce aromatic amino acids via the shikimic acid pathway. Strains of Escherichia coli specifically engineered for overproducing quinic acid from glucose have also been …show more content…
For example, a novel synthesis route has been recently published that obviates raw materials and uses monotrimethylsilyl-acetylene (TMSA) on the easily accessible component 1,4-cyclohexadiene.
Formulations of oseltamivir
Oseltamivir is available in capsules with three dosage options (30, 45, and 75 mg), powder for oral suspension, and in intravenous form (predominately for clinical trials). Both 75 mg capsules and powder formulation have been shown to be bioequivalent dosage forms, and can be stockpiled for use in a pandemic situation.
The capsules can be used for both treatment and prophylaxis in adolescent and adult patients. The powder formulation is primarily intended to enable children to receive the drug, but may also be used by adults who are unable to swallow capsules. Oseltamivir capsules have a shelf life of 5 years, powder formulation 24 months, and reconstituted solution 10 days (if stored at 2 to 8 °C).
Oseltamivir is available to governments in magistral formulation. The active pharmaceutical ingredient is a water-soluble dry powder, with a very long shelf-life when stored in sealed drums. When dissolved in water (15 mg/mL) the solution is stable for three weeks if stored not above 25 °C, and for 6 weeks at 5