Saquinavir

Saquinavir
Systematic (IUPAC) name
(2S)-N-[(2S,3R)-4-[(3S)-3-(tert-butylcarbamoyl)-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinolin-2-ylformamido)butanediamide
Clinical data
Trade names Invirase
AHFS/Drugs.com monograph
MedlinePlus a696001
Pregnancy cat. B1 (Australia)
Legal status  ?
Pharmacokinetic data
Protein binding 98%
Half-life 9 - 15 houres
Identifiers
CAS number 127779-20-8 YesY
ATC code J05AE01
PubChem CID 441243
DrugBank APRD00623
ChemSpider 390016 YesY
UNII L3JE09KZ2F YesY
KEGG D00429 N
ChEMBL CHEMBL114 YesY
Chemical data
Formula C38H50N6O5 
Mol. mass 670.841 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Saquinavir is an antiretroviral drug used in HIV therapy. It falls in the protease inhibitor class. 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, with trade name Fortovase.

Both formulations are generally used as a component of highly active antiretroviral therapy (HAART).

Contents

History

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, and the FDA rushed Invirase to market in light of the dire conditions of the HIV/AIDS epidemic that prevailed at the time and there was a lot of pressure to produce products quickly.[citation needed]

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. [1]

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.

Adverse reactions

The most frequent adverse events with saquinavir in either formulation are mild gastrointestinal symptoms, including diarrhea, 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.[2]

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.

Unlike other protease inhibitors, the absorption of saquinavir seems to be improved by omeprazole.[3]

References

  1. ^ Withdrawal of Fortovase (PDF)
  2. ^ FortovaseTM (saquinavir) soft gelatin capsules. Product information (November 1997)
  3. ^ Winston A, Back D, Fletcher C et al. (2006). "Effect of omeprazole on the pharmacokinetics of saquinavir-500 mg formulation with ritonavir in healthy male and female volunteers". AIDS 20 (10): 1401–6. doi:10.1097/01.aids.0000233573.41597.8a. PMID 16791014. 

Further reading

  • Cohen Stuart JW, Schuurman R, Burger DM, et al. (1999) Randomized trial comparing saquinavir soft gelatin capsules versus indinavir as part of triple therapy (CHEESE study). AIDS 13:F53-58
  • Dragsted UB, Gerstoft J, Pedersen C, et al. (2003) Randomized trial to evaluate indinavir/ritonavir versus saquinavir/ritonavir in human immunodeficiency virus type 1-infected patients: the MaxCmin 1 Trial. J Infect Dis 188:635-642
  • Actual photo of saquinavir and more saquinavir information.

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Look at other dictionaries:

  • Saquinavir — Saltar a navegación, búsqueda Saquinavir …   Wikipedia Español

  • Saquinavir — Structure chimique du saquinavir Général Nom IUPAC (2S) N [(2S,3R) 4 [(3S) 3 (tert …   Wikipédia en Français

  • saquinavir — Antirretroviral inhibidor de la proteasa. Indicaciones: se prescribe en el tratamiento del síndrome de inmunodeficiencia adquirida. Contraindicaciones: el fármano no debe administrarse a pacientes con escasa biodisponibilidad. Efectos adversos:… …   Diccionario médico

  • Saquinavir — Strukturformel Allgemeines Freiname Saquinavir Andere Namen …   Deutsch Wikipedia

  • saquinavir — noun a weak protease inhibitor (trade name Invirase) used in treating HIV • Syn: ↑Invirase • Hypernyms: ↑protease inhibitor, ↑PI * * * saquinavir /sə kwinˈə vir/ noun A protease inhibitor used as a drug in the treatment of HIV …   Useful english dictionary

  • saquinavir — noun Etymology: sa (perhaps backward spelling of protease) + quinoline + avir, alteration of ovir (as in acyclovir) Date: 1994 a protease inhibitor C38H50N6O5 that is administered in the form of its methylated sulfonic salt especially in… …   New Collegiate Dictionary

  • saquinavir — sa·quin·a·vir (sə kwĭnʹə vîr) n. A protease inhibiting drug usually used in combination with other drugs to suppress the replication of HIV.   [saquin (perhaps alteration of (i)soquin(oline): iso + quinoline) + antiviral.] * * * …   Universalium

  • saquinavir — noun An anti retroviral drug of the protease inhibitor class that is used in to treat HIV infected patients …   Wiktionary

  • saquinavir — sa·quin·a·vir sə kwin ə .vir n a protease inhibitor C38H50N6O5 or its mesylate C38H50N6O5·CH4O3S administered orally often in combination with other antiretroviral drugs to treat HIV infection * * * n. see protease inhibitor * * * sa·quin·a·vir… …   Medical dictionary

  • saquinavir — n.; see protease inhibitor …   The new mediacal dictionary

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