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1. Invirase
2. Monomethanesulfonate, Saquinavir
3. Ro 31 8959
4. Ro 31-8959
5. Ro 318959
6. Saquinavir Mesylate
7. Saquinavir Monomethanesulfonate
8. Saquinivir
1. 127779-20-8
2. Invirase
3. Fortovase
4. Ro 318959
5. Ro-31-8959
6. Ro 31-8959
7. Chebi:63621
8. Ro 31-8959/000
9. L3je09kz2f
10. (2s)-n-[(2s,3r)-4-[(3s,4as,8as)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1h-isoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinoline-2-carbonylamino)butanediamide
11. Sch-52852
12. (s)-n1-((2s,3r)-4-((3s,4as,8as)-3-(tert-butylcarbamoyl)octahydroisoquinolin-2(1h)-yl)-3-hydroxy-1-phenylbutan-2-yl)-2-(quinoline-2-carboxamido)succinamide
13. Roc
14. Fortovase(tm)
15. Fortovase (tn)
16. (2s)-n-[(1s,2r)-3-[(3s,4as,8as)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1h-isoquinolin-2-yl]-1-benzyl-2-hydroxy-propyl]-2-(quinoline-2-carbonylamino)butanediamide
17. (2s)-n-[(2s,3r)-4-[(2s,3s,4as,8as)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1h-isoquinolin-2-yl]-3-hydroxy-1-phenyl-butan-2-yl]-2-(quinolin-2-ylcarbonylamino)butanediamide
18. (s)-n-((is)-i-((1r)-2-((3s,4as,8as)-3-(tert-butylcarbamoyl)octahydro-2(1h)-isoquinolyl)-1-hydroxyethyl)phenethyl)-2-quinaldamidosuccinamide
19. Butanediamide, N1-[(1s,2r)-3-[(3s,4as,8as)-3-[[(1,1-dimethylethyl)amino]carbonyl]octahydro-2(1h)-isoquinolinyl]-2-hydroxy-1-(phenylmethyl)propyl]-2-[(2-quinolinylcarbonyl)amino]-, (2s)-
20. N(1)-{(2s,3r)-4-[(3s,4as,8as)-3-(tert-butylcarbamoyl)octahydroisoquinolin-2(1h)-yl]-3-hydroxy-1-phenylbutan-2-yl}-n(2)-(quinolin-2-ylcarbonyl)-l-aspartamide
21. Smr000469157
22. Saquinavir [usan]
23. Unii-l3je09kz2f
24. Invirase(tm)(monomesylate)
25. Ro 31 8959
26. Saquinavirum
27. Saquinavir (jan/usp/inn)
28. Sch 52852
29. Hsdb 7161
30. 1hxb
31. 2fgu
32. 2fgv
33. Saquinavir [usan:usp:inn:ban]
34. (2s)-n-[(2s,3r)-4-[(2s,3s,4as,8as)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1h-isoquinolin-2-yl]-3-hydroxy-1 -phenyl-butan-2-yl]-2-(quinolin-2-ylcarbonylamino)butanediamide
35. Butanediamide, N1-((1s,2r)-3-((3s,4as,8as)-3-(((1,1-dimethylethyl)amino)carbonyl)octahydro-2(1h)-isoquinolinyl)-2-hydroxy-1-(phenylmethyl)propyl)-2-((2-quinolinylcarbonyl)amino)-, (2s)-
36. Saquinavir- Bio-x
37. Plcg-sqv
38. Nsc722663
39. Np-sqv
40. Saquinavir [mi]
41. Saquinavir [inn]
42. Saquinavir [jan]
43. Prestwick0_001114
44. Prestwick1_001114
45. Prestwick2_001114
46. Prestwick3_001114
47. Saquinavir [hsdb]
48. Saquinavir [vandf]
49. Sqv
50. Chembl114
51. Saquinavir [mart.]
52. Schembl6881
53. Saquinavir [who-dd]
54. Saquinavir [who-ip]
55. Bidd:pxr0010
56. Bspbio_001248
57. Mls001195635
58. Mls001304735
59. Bidd:gt0323
60. Saquinavir [ema Epar]
61. Spbio_003114
62. Bpbio1_001373
63. Gtpl4813
64. Sqv-poly(lactide-co-glycolide)
65. Dtxsid6044012
66. Saquinavir [orange Book]
67. Saquinavir [usp Impurity]
68. Hms2232l04
69. Saquinavirum [who-ip Latin]
70. Zinc3914596
71. Bdbm50213021
72. Mfcd00866925
73. Saquinavir-poly(lactide-co-glycolide)
74. Akos000280831
75. Cs-1180
76. Db01232
77. Mrf-0000273
78. Ncgc00091469-02
79. Ncgc00091469-15
80. Ac-26377
81. Bs164390
82. Fortovase; Saquinavir; Ro 31-8959
83. Hy-17007
84. Ro-318959000
85. Ab00514056
86. Ro-31-8959/000
87. D00429
88. 779s208
89. Q422654
90. Brd-k09963420-066-03-4
91. (2s)-n-[(2s,3r)-4-[(2s,3s,4as,8as)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1h-isoquinolin-2-yl]-3-hydroxy-1
92. (2s)-n-[(2s,3r)-4-[(3s,4as,8as)-3-(tert-butylcarbamoyl)-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinolin-2-ylformamido)butanediamide
93. (3s-(2(1r*(r*),2s*),3i,4athetav,8athetav))-n(sup 1)-(3-(3-(((1,1-dimethylethyl)amino)carbonyl)octahydro-2(1h)-isoquinolinyl)-2-hydroxy-1-(phenylmethyl)propyl)-2-((2-quinolinylcarbonyl)amino)butanediamide
94. (s)-n-((.alpha.s)-.alpha.-((1r)-2-((3s,4as,8as)-3-(tert-butylcarbamoyl)octahydro-2(1h)-isoquinolyl)-1-hydroxyethyl)phenethyl)-2-quinaldamidosuccinamide
95. Butanediamide, N(sup 1)-(3-(3-(((1,1-dimethylethyl)amino)carbonyl)octahydro-2(1h)-isoquinolinyl)-2-hydroxy-1-(phenylmethyl)propyl)-2-((2-quinolinylcarbonyl)amino)-, (3s-(2(1r*(r*),2s*),3.alpha.,4a.beta.,8a.beta.))-
96. Butanediamide, N1-(3-(3-(((1,1-dimethylethyl)amino)carbonyl)octahydro-2(1h)-isoquinolinyl)-2-hydroxy-1-(phenylmethyl)propyl)-2-((2-quinolinylcarbonyl)amino)-, (3s-(2(1r*(r*),2s*),3alpha,4aalpha,8aalpha))-
97. N-tert.butyl-decahydro -2- [2(r)-hydroxy-4-phenyl-3(s)-[[n-(2-quinolylcarbonyl) -l-asparaginyl]amino]butyl]-(4as,8as)-isoquinoline-3(s)-carboxamide
98. N-tert.butyl-decahydro-2-[2(r)-hydroxy-4-phenyl-3(s)-[[n-(2-quinolylcarbonyl)-l-asparaginyl]amino]butyl]-(4as,8as)-isoquinoline-3(s)-carboxamide
99. N-tert.butyl-decahydro-2[2(r)-hydroxy-4-phenyl-3-(s)-[[n-(2-quinolylcarbonyl)-l-asparaginyl]amino]butyl]-(4as,8as)-isoquinoline-3(s)-carboxamide
100. N~1~-{(2s,3r)-4-[(3s,4as,8as)-3-(tert-butylcarbamoyl)octahydroisoquinolin-2(1h)-yl]-3-hydroxy-1-phenylbutan-2-yl}-n~2~-(quinolin-2-ylcarbonyl)-l-aspartamide
| Molecular Weight | 670.8 g/mol |
|---|---|
| Molecular Formula | C38H50N6O5 |
| XLogP3 | 4.2 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 13 |
| Exact Mass | 670.38426872 g/mol |
| Monoisotopic Mass | 670.38426872 g/mol |
| Topological Polar Surface Area | 167 Ų |
| Heavy Atom Count | 49 |
| Formal Charge | 0 |
| Complexity | 1140 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 6 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Covalently Bonded Unit Count | 1 |
| 1 of 2 | |
|---|---|
| Drug Name | Invirase |
| PubMed Health | Saquinavir (By mouth) |
| Drug Classes | Antiretroviral Agent |
| Drug Label | INVIRASE brand of saquinavir mesylate is an inhibitor of the human immunodeficiency virus (HIV) protease. INVIRASE is available as light brown and green, opaque hard gelatin capsules for oral administration in a 200-mg strength (as saquinavir free ba... |
| Active Ingredient | Saquinavir mesylate |
| Dosage Form | Tablet; Capsule |
| Route | Oral |
| Strength | eq 500mg base; eq 200mg base |
| Market Status | Prescription |
| Company | Hoffman La Roche; Hoffmann La Roche |
| 2 of 2 | |
|---|---|
| Drug Name | Invirase |
| PubMed Health | Saquinavir (By mouth) |
| Drug Classes | Antiretroviral Agent |
| Drug Label | INVIRASE brand of saquinavir mesylate is an inhibitor of the human immunodeficiency virus (HIV) protease. INVIRASE is available as light brown and green, opaque hard gelatin capsules for oral administration in a 200-mg strength (as saquinavir free ba... |
| Active Ingredient | Saquinavir mesylate |
| Dosage Form | Tablet; Capsule |
| Route | Oral |
| Strength | eq 500mg base; eq 200mg base |
| Market Status | Prescription |
| Company | Hoffman La Roche; Hoffmann La Roche |
Saquinavir, in combination with other antiretroviral agents, is indicated in the treatment of HIV infection or AIDS. Saquinavir soft gelatin capsule (Fortovase) is the preferred dosage form, according to the FDA. /Included in US product labeling/
MICROMEDEX Thomson Health Care. USPDI - Drug Information for the Health Care Professional. 23rd ed. Volume 1. MICROMEDEX Thomson Health Care, Greenwood Village, CO. 2003. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 2439
Saquinavir was not detected in cord blood. Saquinavir soft-gel capsules are well tolerated during pregnancy and are not associated in this small study with birth abnormalities. Transmission of HIV infection from mother to child was successfully prevented in all cases. Low maternal exposures of saquinavir were noted. However, these did not appear to affect virologic efficacy of the combination. Samples from cord blood indicate minimal fetal exposure to saquinavir.
PMID:12138347 Vithayasai V et al; J Acquir Immune Defic Syndr 30 (4): 410-2 (2002)
The principal adverse effects associated with saquinavir therapy involve the GI tract. In adults with HIV infection receiving saquinavir liquid-filled or hard gelatin capsules in conjunction with other antiretroviral agents (e.g., 2 dideoxynucleoside reverse transcriptase inhibitors), diarrhea occurred in 15.6-19.9%, abdominal discomfort in 8.6-13.3%, abdominal pain in 2.3-7.8%, nausea in 10.6-17.8%, dyspepsia in 8.4-8.9%, flatulence in 5.7-12.2%, vomiting in 2.9-4.4%, altered taste in 4.4%, and constipation in 3.3% of patients.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 699
Adverse GI effects reported in <2% of patients receiving saquinavir hard gelatin or liquid-filled capsules alone or in conjunction with other antiretroviral agents include anorexia, abdominal distention, buccal mucosa ulceration, oral canker sores, cheilitis, dry mouth, dysphagia, abdominal colic, esophageal ulceration, esophagitis, eructation, bloodstained or discolored feces, frequent bowel movements, fecal incontinence, gastralgia, gastritis, GI reflux, GI ulcer, GI inflammation, intestinal obstruction, gingivitis, glossitis, hemorrhoids, infectious diarrhea, melena, painful defecation, parotid disorder, pruritus ani, /SRP: heartburn/, stomach upset, pelvic pain, rectal hemorrhage, salivary gland disorder, stomatitis, unpleasant taste, toothache, and tooth disorder.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 699
Headache has occurred in 58.9% of adults with HIV infection receiving saquinavir liquid-filled capsules in conjunction with other antiretroviral agents. Depression has been reported in 2.7%, insomnia in 5.6%, and anxiety or libido disorder in 2.2% of patients receiving saquinavir liquid-filled capsules in conjunction with other antiretroviral therapy.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 700
Adverse nervous system effects that have been reported in less than 2% of patients receiving saquinavir hard gelatin or liquid-filled capsules alone or in conjunction with other antiretroviral agents include ataxia, cerebral hemorrhage, confusion, seizures, dizziness, dysarthria, dysesthesia, facial numbness, facial pain, numbness of the extremities, hyperesthesia, hyperreflexia, hyporeflexia, light-headed feeling, myelopolyradiculoneuritis, paresthesia, peripheral neuropathy, prickly sensation, paresis, poliomyelitis, progressive multifocal leukoencephalopathy, spasms, tremor, and unconsciousness. Adverse psychologic effects reported in less than 2% of patients receiving the drug include agitation, amnesia, anxiety, behavior disturbances, excessive dreaming, euphoria, hallucination, irritability, lethargy, overdose effect, psychic disorder, psychosis, reduced intellectual ability, somnolence, and speech disorder. Serious adverse nervous system effects that have been reported rarely in clinical studies in patients receiving saquinavir alone or in conjunction with other antiretroviral agents which were considered to be at least possibly related to the study drugs include attempted suicide, episodes involving confusion, ataxia and weakness, and headache.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 700
For more Drug Warnings (Complete) data for SAQUINAVIR (23 total), please visit the HSDB record page.
Saquinavir is indicated, in combination with ritonavir and other antiretroviral agents, for the treatment of HIV-1 infection in patients 16 years of age and older.
FDA Label
Invirase is indicated for the treatment of HIV-1-infected adult patients. Invirase should only be given in combination with ritonavir and other antiretroviral medicinal products.
Fortovase is indicated for treatment of HIV-1 infected adult patients. Fortovase should only be given in combination with ritonavir and other antiretroviral medicinal products (see section 4. 2).
Saquinavir exerts its antiviral activity by inhibiting an enzyme critical for the HIV-1 viral lifecycle. Like other protease inhibitors, saquinavir has a propensity for participating in drug interactions - use caution when administering saquinavir to patients maintained on other pharmaceutical agents as pharmacodynamic and pharmacokinetic interactions are common. Saquinavir is known to increase the QTc-interval in otherwise healthy individuals, and should therefore be used with caution in patients maintained on other QTc-prolonging medications or for whom prolongation of the QTc-interval may be of particular consequence (e.g. patients with pre-existing heart disease). Careful and regular monitoring of patient bloodwork is recommended, as saquinavir has been associated with the development of metabolic complications (e.g. diabetes mellitus, hyperlipidemia) and worsening of pre-existing liver disease.
HIV Protease Inhibitors
Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly. (See all compounds classified as HIV Protease Inhibitors.)
Cytochrome P-450 CYP3A Inhibitors
Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP3A. (See all compounds classified as Cytochrome P-450 CYP3A Inhibitors.)
J05AE01
J05AE01
J05AE01
S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355
J - Antiinfectives for systemic use
J05 - Antivirals for systemic use
J05A - Direct acting antivirals
J05AE - Protease inhibitors
J05AE01 - Saquinavir
Absorption
The absolute bioavailability of orally administered saquinavir is only ~4%, thought to be a consequence of incomplete absorption and extensive first-pass metabolism. It is co-administered with ritonavir, another protease inhibitor and a potent inhibitor of the enzymes responsible for saquinavir's first-pass metabolism, in order to dramatically boost its serum concentrations and, by extension, its therapeutic efficacy. Following administration of saquinavir 1000mg twice daily with ritonavir 100mg twice daily the AUC24h at steady-state was 39026 ng.h/mL.
Route of Elimination
The primary means of elimination of saquinavir appears to be extensive hepatic metabolism followed by fecal excretion of both the parent drug and metabolic products. Following the administration of radiolabeled saquinavir (both orally and intravenously), approximately 81-88% of radioactivity is recovered in the feces within 5 days of dosing while only 1-3% is recovered in the urine. Mass balance studies indicate that only 13% of orally-administered plasma radioactivity is attributed to unchanged parent drug, with the remainder comprising metabolic products of saquinavir's hepatic metabolism. In contrast, intravenous administration resulted in approximately 66% of the circulating plasma radioactivity being attributed to unchanged parent drug, suggesting a high degree of first-pass metabolism with oral administration.
Volume of Distribution
The steady-state volume of distribution of saquinavir is approximately 700 L, suggesting extensive distribution into tissues.
Clearance
The systemic clearance of saquinavir is approximately 1.14 L/h/kg following intravenous administration.
Following administration of saquinavir in a dosage of 1200 mg 3 times daily as liquid-filled capsules, mean steady-state AUC at 3 weeks was 7249 ngh/mL compared with an AUC of 866 ngh/mL reported following administration of saquinavir hard gelatin capsules in a dosage of 600 mg 3 times daily. While the AUC of saquinavir in adults receiving liquid-filled capsules was lower at week 61-69 compared with the AUC at week 3, the AUC at week 61-69 was greater than the AUC at the same time point in HIV-infected adults receiving saquinavir as hard gelatin capsules (600 mg 3 times daily).
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 706
The relative oral bioavailability of saquinavir from liquid-filled (soft gelatin) capsules is estimated to average 331% (range: 207-530%) of that achieved with hard gelatin capsules of the drug when single 600-mg doses are administered. This would represent a calculated average oral bioavailability from the liquid-filled capsules of about 13% based on an average absolute bioavailability of 4% from the hard capsules; however, these are calculated estimates and not based on actual determination of absolute oral bioavailability from the liquid-filled capsules.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 706
Saquinavir and its metabolites are eliminated from the body primarily through the biliary system and feces (more than 95% of the drug), with minimal urinary excretion (less than 3% of administered drug).
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1368
Oral bioavailability of the hard-gelatin capsule formulation of saquinavir (saquinavir mesylate, invirase) is only 4% due to limited absorption and extensive first-pass metabolism, with considerable interpatient variability. ... Absorption of saquinavir may be enhanced when the drug is taken with a high-calorie, high-fat meal. In addition, saquinavir demonstrates a greater than dose-proportional increase in exposure. For example, tripling the oral dose of saquinavir is associated with an eightfold increase in exposure.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1367
For more Absorption, Distribution and Excretion (Complete) data for SAQUINAVIR (10 total), please visit the HSDB record page.
Saquinavir is extensively metabolized in the liver following oral administration, and _in vitro_ studies have shown that >90% of its biotransformation is mediated by the CYP3A4 isoenzyme. Saquinavir is rapidly metabolized to a number of inactive mono- and di-hydroxylated compounds.
Results of in vitro studies indicate that saquinavir is rapidly metabolized in the liver to several monohydroxylated and dihydroxylated inactive metabolites. Metabolism of saquinavir is mediated by cytochrome P450; the isoenzyme CYP3A4 is involved in more than 90% of this metabolism. Orally administered saquinavir appears to undergo substantial metabolism on first pass through the liver.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 706
Saquinavir is metabolized primarily by hepatic CYP3A4. The metabolites of saquinavir are not active against HIV-1.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1368
Saquinavir has known human metabolites that include (2S)-N-[(2S,3R)-4-[(3S,4aR,8aS)-3-(tert-butylcarbamoyl)-6-hydroxy-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-[(quinolin-2-yl)formamido]butanediamide, (2S)-N-[(2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-7-hydroxy-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-[(quinolin-2-yl)formamido]butanediamide, and (2S)-N-[(2S,3R)-4-[(3S,4aS,8aS)-3-[(1-hydroxy-2-methylpropan-2-yl)carbamoyl]-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-[(quinolin-2-yl)formamido]butanediamide.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560
The HIV lifecycle is comprised of 3 distinct stages: assembly, involving creation and packaging of essential viral components; budding, wherein the viral particle crosses the host cell plasma membrane and forms a lipid envelope; and maturation, wherein the viral particle alters its structure and becomes infectious. At the center of this lifecycle is the Gag polyprotein which, along with the products of its proteolysis, coordinate these stages and function as the major structural proteins of the virus. The HIV-1 protease enzyme, a dimeric aspartic protease, is the enzyme responsible for cleaving the Gag polyprotein and thus plays a critical role in many aspects of the HIV viral lifecycle. Saquinavir is an inhibitor of the HIV-1 protease enzyme. Its design is based on the "peptidomimetic" principle, wherein the molecule contains a hydroxyethylene scaffold that mimics the normal peptide linkage (cleaved by HIV protease) but which itself cannot be cleaved. By preventing HIV-1 protease activity, and thus the proteolysis of the Gag polyprotein, saquinavir results in the production of immature, non-infectious viral particles.
While the complete mechanisms of antiviral activity of saquinavir have not been fully elucidated, saquinavir apparently inhibits replication of retroviruses, including human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), by interfering with HIV protease. The drug, therefore, exerts a virustatic effect against retroviruses by acting as an HIV protease inhibitor.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 704
Saquinavir is a selective, competitive, reversible inhibitor of HIV protease. HIV protease, an aspartic endopeptidase that functions as a homodimer, plays an essential role in the replication cycle of HIV and the formation of infectious virus. During HIV replication, HIV protease cleaves viral polypeptide products of the gag and gag-pol genes (i.e., p55 and p160) to form structural proteins of the virion core (i.e., p17, p24, p9, and p7) and essential viral enzymes (i.e., reverse transcriptase, integrase, and protease). Because saquinavir is a structural analog of the HIV Phe-Pro protease cleavage site, the drug inhibits the function of the enzyme. By interfering with the formation of these essential proteins and enzymes, saquinavir blocks maturation of the virus and causes the formation of nonfunctional, immature, noninfectious virions. Saquinavir is active in both acutely and chronically infected cells since it targets the HIV replication cycle after translation and before assembly. Thus, the drug is active in chronically infected cells (e.g., monocytes and macrophages) that generally are not affected by nucleoside reverse transcriptase inhibitors (e.g., didanosine, lamivudine, stavudine, zalcitabine, zidovudine). Saquinavir does not affect early stages of the HIV replication cycle; however, the drug interferes with the production of infectious HIV and limits further infectious spread of the virus.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 704
Unlike nucleoside antiretroviral agents, the antiviral activity of saquinavir does not depend on intracellular conversion to an active metabolite. Saquinavir and other HIV protease inhibitors (e.g., amprenavir, indinavir, lopinavir, nelfinavir, ritonavir) act at a different stage of the HIV replication cycle than nucleoside and nonnucleoside reverse transcriptase inhibitors, and results of in vitro studies indicate that the antiretroviral effects of some nucleoside reverse transcriptase inhibitors and HIV protease inhibitors may be additive or synergistic.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2003 (Plus Supplements)., p. 704
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