To use all functions of this page, please activate cookies in your browser.
With an accout for my.bionity.com you can always see everything at a glance – and you can configure your own website and individual newsletter.
- My watch list
- My saved searches
- My saved topics
- My newsletter
Both formulations are generally used as a component of highly active antiretroviral therapy (HAART).
Saquinavir was the first protease inhibitor (and sixth antiretroviral) approved by the Food and Drug Administration (FDA). It was approved on December 6, 1995, as Invirase®, a poorly-absorbed hard gel capsule which quickly led to viral resistance in many of the pioneer patients. The manufacturer, Roche, is alleged to have rushed Invirase® to market, but the conditions that prevailed at the time were very bad and there was a lot of pressure to produce products quickly.
It was approved again on Nov 7, 1997 as Fortovase®, a soft gel capsule reformulated for improved bioavailability. Roche announced in May 2005 that, owing to reduction in demand, Fortovase® would cease being marketed early in 2006 in favour of Invirase® boosted with ritonavir. 
Mode of action
Saquinavir is a protease inhibitor. Proteases are enzymes that cleave protein molecules into smaller fragments. HIV protease is vital for both viral replication within the cell and release of mature viral particles from an infected cell. Saquinavir inhibits both HIV-1 and HIV-2 proteases.
The most frequent adverse events with saquinavir in either formulation are mild gastrointestinal symptoms, including diarrhoea, nausea, loose stools & abdominal discomfort. Invirase is better tolerated than Fortovase.
Bioavailability and drug interactions
Saquinavir, in the Invirase® formulation, has a low and variable oral bioavailability, when given alone. The Fortovase® formulation at the standard dosage delivers approximately eightfold more active drug than Invirase®, also at the standard dosage.
In the clinic, it was found that the oral bioavailability of saquinavir in both formulations significantly increases when patients also receive the PI ritonavir. For patients, this has the major benefit that they can take less saquinavir, while maintaining sufficient saquinavir blood plasma levels to efficiently suppress the replication of HIV.
The mechanism behind this welcome observation was not directly known, but later it was determined that ritonavir inhibits the cytochrome P450 3A4 isozyme. Normally, this enzyme metabolizes saquinavir to an inactive form, but with the ritonavir inhibiting this enzyme, the saquinavir blood plasma levels increased considerably. Additionally, ritonavir also inhibits multidrug transporters, although to a much lower extent.
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Saquinavir". A list of authors is available in Wikipedia.|