Saquinavir
Clinical data | |
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Trade names | Invirase, Fortovase |
Other names | SQV |
AHFS/Drugs.com | Monograph |
MedlinePlus | a696001 |
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By mouth | |
ATC code | |
Legal status | |
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Pharmacokinetic data | |
Bioavailability | ~4% (without ritonavir boosting)[3] |
Protein binding | 98% |
Metabolism | Liver, mainly by CYP3A4 |
Elimination half-life | 9–15 hours |
Excretion | feces (81%) and urine (3%) |
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Saquinavir, sold under the brand name Invirase among others, is an
Common side effects include nausea, vomiting, diarrhea, and feeling tired.
Saquinavir was patented in 1988 and first sold in 1995.[5][6]
Medical uses
Saquinavir is used together with other medications to treat or prevent HIV/AIDS.[4] Typically it is used with ritonavir or lopinavir/ritonavir to increase its effect.[4]
Side effects
The most frequent adverse events with saquinavir in either formulation are mild gastrointestinal symptoms, including
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.[7]
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.[medical citation needed]
The mechanism behind this welcome observation was not directly known, but later it was determined that ritonavir inhibits the
Unlike other protease inhibitors, the absorption of saquinavir seems to be improved by omeprazole.[8]
Mechanism 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 binds to the active site of the viral protease and prevents cleavage of viral polyproteins, preventing maturation of the virus. Saquinavir inhibits both HIV-1 and HIV-2 proteases.[9]
History
Saquinavir was developed by the pharmaceutical company
Roche requested and received approval of Invirase via the FDA's "Accelerated Approval" program—a process designed to speed drugs to market for the treatment of serious diseases—a decision that was controversial, as AIDS activists disagreed over the benefits of thorough testing versus early access to new drugs.
Society and culture
Economics
As of 2015[update], it is not available as a
Formulations
Two formulations have been marketed:
- a hard-gel capsule formulation of the mesylate, with trade name Invirase, which requires combination with ritonavir to increase the saquinavir bioavailability;
- a soft-gel capsule formulation of saquinavir (microemulsion,[18] orally-administered formulation), with trade name Fortovase, which was discontinued worldwide in 2006.[19]
References
- ^ "Saquinavir Use During Pregnancy". Drugs.com. 20 March 2018. Retrieved 28 January 2020.
- ^ Roche Products Pty Limited (6 November 2018). "Invirase® (Saquinavir mesilate)". Australian Product Information – via MedAdvisor International Pty Ltd.
- ^ "Invirase- saquinavir mesylate capsule INVIRASE- saquinavir mesylate tablet, film coated". DailyMed. 26 December 2019. Retrieved 28 January 2020.
- ^ a b c d e f g h i "Saquinavir". The American Society of Health-System Pharmacists. Archived from the original on 8 September 2015. Retrieved 5 September 2015.
- ISBN 9781420015706. Archivedfrom the original on 31 March 2016.
- ISBN 9783527607495.
- ^ "Fortovase". Drugs.com. 22 March 2019. Archived from the original on 28 April 2020. Retrieved 28 January 2020.
- S2CID 44506039.
- ISBN 9780443075926.
- ^ from the original on 9 November 2013. Retrieved 8 November 2013.
- ^ Hilts PJ (8 December 1995). "F.D.A. Backs A New Drug To Fight AIDS". New York Times. Retrieved 28 October 2020.
- ^ "Antiretroviral Drug Discovery and Development". NIH. 26 November 2018. Retrieved 29 October 2020.
- ^ The CDC, in its Morbidity and Mortality Weekly Report, ascribes this to "highly active antiretroviral therapy", without mention of either of these drugs, see the preceding citation. A further citation is needed to make this accurate connection between this drop and the introduction of the protease inhibitors.
- ^ AIDS Community Research Initiative of America. "Drugs! Drugs! Drugs! An Overview of the Approved Anti-HIV Medications". The Body. Archived from the original on 9 November 2013. Retrieved 20 February 2013.
- ^ "Drug Approval Package: Fortovase/Saquinavir NDA 20828". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 28 January 2020.
- ^ "Withdrawal of Fortovase (PDF)" (PDF). Archived from the original (PDF) on 14 May 2006.
- ^ "Generic Invirase Availability". Drugs.com. Retrieved 9 July 2020.
- S2CID 28468973.
- ^ "Roche to discontinue the sale and distribution of Fortovase (saquinavir)". News-Medical.Net. 18 May 2005. Archived from the original on 22 February 2015.
External links
- "Saquinavir". Drug Information Portal. U.S. National Library of Medicine.