Medical Advocates

Saquinavir (Fortovase/Invirase)
Journal Citations

General Reports
Viral Dynamics
Drug/Drug Interactions
Adverse Events
Drug Monitoring

Adolescent/Adult Indications
Perinatal Index
Pediatric Index

Saquinavir Main Page Main New/Newsworthy  Home Page

Last Update:  October 10, 2016
 Documents identified with this icon are in Portable Document Format (PDF) and require the Adobe Acrobat Reader
Perinatal data are integrated with Perinatal Conference Data in the Perinatal Data Page
Pediatric data are integrated with Pediatric Conference Data in the Pediatric Data Page

General Reports

Saquinavir Induced Suicidal Death of Human Erythrocytes.
Waibel S, Bissinger R, Bouguerra G, et al   
Cell Physiol Biochem
. 2015;37(5):1973-1982.

The HIV protease inhibitor saquinavir inhibits HMGB1 driven inflammation by targeting the interaction of cathepsin V with TLR4/MyD88
Pribis JP, Al-Abed Y, Yang H,  et al
Mol Med
. 2015 Sep 2.

Development and characterization of folate anchored Saquinavir entrapped PLGA nanoparticles for anti-tumor activity.
Singh R, Kesharwani P, Mehra NK,  et al
Drug Dev Ind Pharm
. 2015 Mar 4:1-14

Investigation on the stability of saquinavir loaded liposomes: Implication on stealth, release characteristics and cytotoxicity.
Ramana LN, Sharma S, Sethuraman S, et al
Int J Pharm
. 2012 Apr 28

Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL.
Mojic M, Mijatovic S, Maksimovic-Ivanic D,  et al
 F.Cell Cycle. 2012 Mar 15;11(6).

Saquinavir inhibits the malaria parasite's chloroquine resistance transporter.
Martin RE, Butterworth AS, Gardiner DL, et al
Antimicrob Agents Chemother. 2012 Feb 21.

Ritonavir or saquinavir impair the invasion of cervical intraepithelial neoplasia cells via a reduction of MMP
expression and activity.
Barillari G, Iovane A, Bacigalupo I, et al
. 2012 Feb 4.

Bioequivalence study of two oral tablet formulations containing saquinavir mesylate boosted with ritonavir in healthy male subjects.
Yerino GA, Halabe EK, Zini E, Feleder EC.
. 2011;61(8):481

Solid lipid nanoparticles comprising internal Compritol 888 ATO, tripalmitin and cacao butter for encapsulating and
releasing stavudine, delavirdine and saquinavir.
Kuo YC, Chung CY.
Colloids Surf B Biointerfaces
. 2011

Randomized comparison of metabolic and renal effects of saquinavir/r or atazanavir/r plus tenofovir/emtricitabine in
treatment-naďve HIV-1-infected patients.
Vrouenraets S, Wit F, Fernandez Garcia E, et al
. 2011 Aug 7.

Cytotoxic and immune-sensitizing properties of nitric oxide-modified saquinavir in
iNOS-positive human melanoma cells.
Mijatovic S, Maksimovic-Ivanic D, Mojic M. et al
J Cell Physiol. 2011 Jul;226(7):1803-12.

In vitro and in vivo anticancer action of Saquinavir-NO, a novel nitric oxide-derivative of the
protease inhibitor saquinavir, on hormone resistant prostate cancer cells.
Donia M, Maksimovic-Ivanic D, Mijatovic S,  et al
Cell Cycle
. 2011 Feb 1;10(3).

Cytotoxic and immune-sensitizing properties of nitric oxide-modified saquinavir in
iNOS-positive human melanoma cells.
Mijatovic S, Maksimovic-Ivanic D, Mojic M, et al

J Cell Physiol
. 2010 Nov 10

Modulation of endocrine and transport functions in human trophoblasts by saquinavir and nelfinavir.
Beghin D, Forestier F, Noël-Hudson MS,  et al
Eur J Obstet Gynecol Reprod Biol. 2010 Jun 28.

Enhancing the Delivery of Anti Retroviral Drug "Saquinavir" Across the
Blood Brain Barrier using Nanoparticles.
Mahajan SD, Roy I, Xu G, et al
Curr HIV Res
. 2010 Apr 29.

Effect of saquinavir/ritonavir on P-glycoprotein activity in healthy volunteers
using digoxin as a probe.
Schmitt C, Kaeser B, Riek M. et al 
Int J Clin Pharmacol Ther
. 2010 Mar;48(3):192-9.

Saquinavir, the pioneer antiretroviral protease inhibitor.
a Porte CJ.
Expert Opin Drug Metab Toxicol. 2009 Sep 8.

Effect of saquinavir/ritonavir (1000/100 mg bid) on the pharmacokinetics of methadone
in opiate-dependent HIV-negative patients on stable methadone maintenance therapy.
Jamois C, Smith P, Morrison R, et al 
Addict Biol. 2009 Jul;14(3):321-7.

Reducing the boosting dose of ritonavir does not affect saquinavir plasma concentrations in
HIV-1-infected individuals.
van der Lugt J, Gorowara M, Avihingsanon A, et al
AIDS. 2009 Jun 1;23(9):1176-1179.

The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt.
Maksimovic-Ivanic D, Mijatovic S, Miljkovic D, et al 
Mol Cancer Ther. 2009 May 5

Saquinavir exposure in HIV-infected patients with chronic viral hepatitis.
Moltó J, Llibre JM, Ribera E, et al 
J Antimicrob Chemother
. 2009 Mar 11

The HIV protease inhibitor saquinavir induces endoplasmic reticulum stress, autophagy, and
apoptosis in ovarian cancer cells.
McLean K, VanDeVen NA, Sorenson DR, Daudi S, Liu JR. 
Gynecol Oncol
. 2009 Mar;112(3):623-30.
The HIV protease inhibitor saquinavir induces endoplasmic reticulum stress, autophagy,
and apoptosis in ovarian cancer cells.
McLean K, Vandeven NA, Sorenson DR, et al
Gynecol Oncol
. 2009 Jan 14

Rate limiting steps in hepatic drug clearance: comparison of hepatocellular uptake and
metabolism with microsomal metabolism of saquinavir, nelfinavir and ritonavir.

Parker A, Houston JB.
Drug Metab Dispos
. 2008 Apr 21
Immunomodulatory effects of two HIV protease inhibitors, Saquinavir and Ritonavir, on lymphocytes
from healthy seronegative individuals.

Delmonte OM, Bertolotto G, Ricotti E, Tovo PA.
Immunol Lett. 2007 Jul 27;
Improved oral bioavailability and brain transport of Saquinavir upon administration in novel
nanoemulsion formulations.

Vyas TK, Shahiwala A, Amiji MM.
Int J Pharm.
2007 Jun 19;
Transport of stavudine, delavirdine, and saquinavir across the blood-brain barrier by
polybutylcyanoacrylate, methylmethacrylate-sulfopropylmethacrylate, and solid lipid

Kuo YC, Su FL
Int J Pharm
. 2007 Mar 12
Delivery of Saquinavir in Biodegradable Polymeric Nanoparticles for HIV/AIDS.
Shah LK, Amiji MM.
Pharm Res.
2006 Sep 13
Saquinavir/Ritonavir: its evolution and current treatment role.
O'Brien WA 3rd. 
AIDS Read. 2006 Jan;16(1):38-44;


Effect of a Modified Saquinavir/Ritonavir Dosing Regimen with Lower Dose Lead-In Phase on QTc Interval, Pharmacokinetics, Antiviral Activity and Safety in Treatment-Naďve HIV-1-Infected Patients.
Boffito M, Jackson A, Pozniak A,  et al
. 2015 Mar 6.

Population pharmacokinetics of ritonavir-boosted saquinavir regimens in HIV-infected individuals.
Dickinson L, Boffito M, Back DJ, et al 
J Antimicrob Chemother.
2008 Sep 29.

Pharmacokinetic analysis to assess forgiveness of boosted saquinavir regimens for missed or late dosing.
Dickinson L, Boffito M, Khoo SH, et al
J Antimicrob Chemother. 2008 May 7
Pharmacokinetics and Safety of Saquinavir/Ritonavir and Omeprazole in HIV-infected
Singh K, Dickinson L, Chaikan A, et al 
Clin Pharmacol Ther.
2007 Sep 26;
CYP3A5 Genotype has an Impact on the Metabolism of the HIV Protease Inhibitor
Josephson F, Allqvist A, Janabi M, et al 
Clin Pharmacol Ther.
2007 Feb 28;
Pharmacokinetics of saquinavir, atazanavir and ritonavir in a boosted double-protease
inhibitor twice-daily regimen.
von Hentig N, Muller A, Rottmann C, et al
Antimicrob Agents Chemother. 2007 Feb 12;
Saquinavir, nelfinavir and M8 pharmacokinetics following combined saquinavir, ritonavir
and nelfinavir administration.

Stocker H, Herzmann C, Breske A, et al 
J Antimicrob Chemother. 2007 Jan 25
Estimation of Population Pharmacokinetic Parameters of Saquinavir in HIV Patients with the
MONOLIX Software.

Lavielle M, Mentre F  
J Pharmacokinet Pharmacodyn. 2007 Jan 9;
Influence of atazanavir 200 mg on the intracellular and plasma pharmacokinetics
of saquinavir and ritonavir 1600/100 mg administered once daily in HIV-infected patients.

Ford J, Boffito M, Maitland D, et al
J Antimicrob Chemother.
2006 Sep 19;
Gender: A Possible Determinant in Dosing of Dermatologic Drugs-an overview.
Modjtahedi BS, Modjtahedi SP, Maibach HI.
Cutan Ocul Toxicol.
Pharmacokinetics of Saquinavir Hard-Gel/Ritonavir and Atazanavir When Combined Once Daily
in HIV Type 1-Infected Individuals Administered Different Atazanavir Doses.
Boffito M, Maitland D, Dickinson L, et al
AIDS Res Hum Retroviruses. 2006 Aug;22(8):749-56.
Effect of omeprazole on the pharmacokinetics of saquinavir-500 mg formulation with ritonavir
in healthy male and female volunteers.

Winston A, Back D, Fletcher C. et al 
. 2006 Jun 26;20(10):1401-6.

Ritonavir, Saquinavir and Efavirenz, but not Nevirapine, Inhibit Bile Acid Transport in Human
and Rat Hepatocytes.
McRae MP, Lowe CM, Tian X ,  et al
J Pharmacol Exp
Ther. 2006 May 23;


Interindividual variability of once-daily ritonavir boosted saquinavir pharmacokinetics in
Thai and UK patients.
Autar RS, Boffito M, Hassink E, et al
J Antimicrob Chemother. 2005 Oct 4;
Steady-State Pharmacokinetics of a Double-Boosting Regimen of Saquinavir Soft Gel plus
Lopinavir plus Minidose Ritonavir in Human Immunodeficiency Virus-Infected Adults.
Ribera E, Lopez RM, Diaz M,et al
Antimicrob Agents Chemother. 2004 Nov;48(11):4256-4262.
Steady-State Pharmacokinetics of Saquinavir Hard-Gel/Ritonavir/Fosamprenavir in
HIV-1-Infected Patients.
Boffito M, Dickinson L, Hill A, et al 
J Acquir Immune Defic Syndr. 2004 Nov 1;37(3):1376-1384.
Pharmacokinetic study of saquinavir hard gel caps/ritonavir in HIV-1-ifnfected patients:
1600/100 mg once-daily compared with 2000/100 mg once-daily and 1000/100 mg

Autar RS, Ananworanich J, Apateerapong W, et al;
J Antimicrob Chemother. 2004 Aug 25
Multidrug resistance protein 1-mediated transport of saquinavir by microglia.
Dallas S, Ronaldson PT, Bendayan M, Bendayan R. 
Neuroreport. 2004 May 19;15(7):1183-6.

Sex-based differences in saquinavir pharmacology and virologic response in
AIDS clinical trials group study 359.
Fletcher CV, Jiang H, Brundage RC,et al 
J Infect Dis. 2004 Apr 1;189(7):1176-84.

Saquinavir induces stable and functional expression of the multidrug transporter |
P-glycoprotein in human CD4 T-lymphoblastoid CEMrev cells.
Dupuis ML, Flego M, Molinari A, Cianfriglia M.
HIV Med.
2003 Oct;4(4):338-345

Pharmacokinetics of Once-Daily Saquinavir Hard-Gelatin Capsules and Saquinavir
 Soft-Gelatin Capsules Boosted With Ritonavir in  HIV-1-Infected Subjects.

Cardiello PG, Monhaphol T, Mahanontharit A, et al  
JAcquir Immune Defic Syndr
2003 Apr 1;32(4):375-9


Pharmacokinetics of saquinavir co-administered with cimetidine.
Boffito M, Carriero P, Trentini L, et al.
J Antimicrob Chemother
2002 Dec;50(6):1081-4
Model-based Analysis of the Pharmacokinetic Interactions Between Ritonavir, Nelfinavir, and
Saquinavir after Simultaneous and Staggered Oral Administration
Lu JF, Blaschke TF, Flexner C, et al
Drug Metab Dispos 2002 Dec;30(12):1455-61


Transepithelial transport of prodrugs of the HIV protease inhibitors saquinavir, indinavir, and
nelfinavir across Caco-2 cell monolayers.
Rouquayrol M, Gaucher B, Roche D, Greiner J, Vierling P.
Pharm Res 2002 Nov;19(11):1704-12
The unbound percentage of saquinavir and indinavir remains constant throughout the dosing
interval in HIV positive subjects.

Boffito M, Hoggard PG, Reynolds HE, et al.
Br J Clin Pharmacol 2002 Sep;54(3):262-8
A pharmacokinetic study of intermittent rifabutin dosing with a combination of ritonavir and
saquinavir in patients infected with human immunodeficiency virus
Gallicano K, Khaliq Y, Carignan G, Tseng A, et al.
lin Pharmacol Ther 2001 Aug;70(2):149-158
The effect of garlic supplements on the pharmacokinetics of saquinavir.
Piscitelli SC, Burstein AH, Welden N, et al.
Clin Infect Dis 2002 Jan 15;34(2):234-8


Viral Dynamics

  Viral Decay Dynamics in HIV-Infected Patients Receiving Ritonavir-Boosted Saquinavir and
Efavirenz With or Without Enfuvirtide: A Randomized, Controlled Trial (HIV-NAT 012).
Boyd MA, Dixit NM, Siangphoe U, et al  
J Infect Dis. 2
006 Nov 1;194(9):1319-22.
Saquinavir drug exposure is not impaired by the boosted double protease inhibitor combination
of lopinavir/ritonavir

Stephan C, Hentig N, NiKourbeti I, et al
AIDS: Vol 18(3) 20 February 2004 pp 503-508
Baseline antiretroviral drug susceptibility influences treatment response in patients receiving
saquinavir-enhancing therapy.
Middleton T, Smith D, Larder B,  et al
HIV Clin Trials 2001 Nov-Dec;2(6):445-52

PDF Paper
The insufficient suppression of viral load by saquinavir hard gel is reversible: a retrospective
cohort study.
Jensen-Fangel S, Kirk O, Blaxhult A,  et al
HIV Clin Trials 2001 Mar-Apr;2(2):122-7
PDF Paper


A Contribution to the Drug Resistance Mechanism of Darunavir, Amprenavir, Indinavir, and Saquinavir Complexes with HIV-1 Protease Due to Flap Mutation I50V: A Systematic MM-PBSA and Thermodynamic Integration Study.
Leonis G, Steinbrecher TB, Papadopoulos MG.
J Chem Inf Model. 2013 Jul 8

Impact of drug transporters on cellular resistance towards saquinavir and darunavir.
König SK, Herzog M, Theile D,  et al
J Antimicrob Chemother
. 2010 Sep 3

Insights into the mechanism of drug resistance: X-ray structure analysis of
G48V/C95F tethered HIV-1 protease dimer/saquinavir complex.
Prashar V, Bihani SC, Das A,  et al 
Biochem Biophys Res Commun. 2010 May 12


Absence of resistance mutations in antiretroviral-naive patients treated with ritonavir-boosted
Ananworanich J, Hirschel B, Sirivichayakul S, Ubolyam S, et al 
Antivir Ther. 2006;11(5):631-5

  Analysis of genotypic and phenotypic clinical cut-off levels for ritonavir-boosted saquinavir.
Hill A, Walmsley S, Clotet B, Molto J.
HIV Med. 2006 Mar;7(2):67-74.
  Clinically relevant interpretation of genotype and relationship to plasma drug
concentrations for resistance to saquinavir-ritonavir in human immunodeficiency
virus type 1 protease inhibitor-experienced patients.
Marcelin AG, Dalban C, Peytavin G, et al 
Antimicrob Agents Chemother. 2004 Dec;48(12):4687-92.
  Pharmacokinetics and resistance mutations affect virologic response to ritonavir/saquinavir-
containing regimens.

Pellegrin I, Breilh D, Birac V, et al.
Ther Drug Monit 2001 Aug;23(4):332-340
Human Immunodeficiency Virus Type1 Protease Cleavage Site Mutations Associated with
Protease Inhibitor Cross-Resistance Selected by Indinavir, Ritonavir, and/or Saquinavir

Cote HC, Brumme ZL, Harrigan PR
Antimicrob Agents Chemother 2000 Oct;44(10):2672-2678

Adverse Events

Unexpected Hepatotoxicity of Rifampin and Saquinavir/Ritonavir in Healthy Male Volunteers.
Schmitt C, Riek M, Winters K, et al
Arch Drug Inf. 2009 Mar;2(1):8-16.

Association of saquinavir plasma concentrations with side effects but not with antiretroviral
outcome in patients infected with protease inhibitor susceptible HIV-1.

Lötsch J, Harder S, Geisslinger G, et al
Antimicrob Agents Chemother.
2007 Jun 18; 
  Dose reduction effective in alleviating symptoms of saquinavir toxicity.
Stephan C, Carlebach A, Rottmann C, et al  
Int J STD AIDS. 2007 Feb;18(2):81-4.
  Therapeutic Dose of HIV-1 Protease Inhibitor Saquinavir does not Permanently Influence Early
Insulin Signaling.
Algenstaedt P, Daneshi S, Schwarzloh B, et al 
Exp Clin Endocrinol Diabetes. 2003 Dec;111(8):491-8.
  The HIV protease inhibitor saquinavir impairs lipid metabolism and glucose transport in cultured
Ranganathan S, Kern PA.
J Endocrinol 2002 Jan;172(1):155-62


  The HIV-protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines.
Bandiera E, Todeschini P, Romani C, et al
Oncol Lett. 2016 Oct;12(4):2493-2500

Pharmacokinetics of Two Randomized Trials Evaluating the Safety and Efficacy of Indinavir,
Saquinavir and Lopinavir in Combination with Low-Dose Ritonavir: The MaxCmin1 and 2 Trials.

Justesen US, Fox Z, Pedersen C, et al
Basic Clin Pharmacol Toxicol. 2007 Nov;101(5):339-44.

  Clinical and pharmacokinetic data support once-daily low-dose boosted saquinavir
(1200/100 mg) in naive or limited PI-experienced HIV-infected patients.
Marin-Niebla A, Lopez-Cortes LF, Ruiz-Valderas R, et al
Antimicrob Agents Chemother. 2007 Mar 19;
Cerebrospinal fluid HIV-1 RNA, intrathecal immunoactivation, and drug concentrations after
treatment with a combination of saquinavir, nelfinavir, and two nucleoside analogues: the
M61022 study.
Yilmaz A, Fuchs D, Hagberg L, Nillroth U, et a
BMC Infect Dis. 2006 Mar 27;6(1):63
  The 48-week efficacy of once-daily saquinavir/ritonavir in patients with undetectable
viral load after 3 years of antiretroviral therapy.
Cardiello P, Srasuebkul P, Hassink E,et al  
HIV Med. 2005 Mar;6(2):122-8
  Short-course induction with boosted saquinavir monotherapy for naive patients with late-stage
Ebrahim O, Hill A
AIDS. 2005 Jan 28;19(2):211-2.
  Intracellular and plasma pharmacokinetics of saquinavir-ritonavir, administered at 1,600/100
milligrams once daily in human immunodeficiency virus-infected patients.
Ford J, Boffito M, Wildfire A 
Antimicrob Agents Chemother.
2004 Jul;48(7):2388-93.

Drug Monitoring

Evidence-based Therapeutic Drug Monitoring for Saquinavir
Muret P, Solas C.
Therapie. 2011 May-Jun;66(3):207-12.

Predictive value of drug levels, HIV genotyping, and the genotypic inhibitory quotient (GIQ) on
response to saquinavir/ritonavir in antiretroviral-experienced HIV-infected patients.

Valer L, Mendoza CD, Soriano V.
Med Virol. 2005 Oct 27;77(4):460-464


Drug monitoring and viral response to Lopinavir/Ritonavir or Saquinavir/Ritonavir containing
regimens in individuals infected with the human immunodeficiency virus type 1.
Falkensammer B, Fasser W, Scherer K, et al 
Int J Immunopathol Pharmacol. 2005 January-March;18(1):145-154
Determination of saquinavir and ritonavir in human plasma by reversed-phase high-
performance liquid chromatography and the analytical error function.
Albert V, Modamio P, Lastra CF, Marino EL.
J Pharm Biomed Anal.
2004 Nov 19;36(4):835-840.



A liquid chromatography-tandem mass spectrometry assay for quantification of nevirapine,
indinavir, atazanavir, amprenavir, saquinavir, ritonavir, lopinavir, efavirenz, tipranavir, darunavir
and maraviroc in the plasma of patients infected with HIV.
Martin J, Deslandes G, Dailly E, et al 
J Chromatogr B Analyt Technol Biomed Life Sci
. 2009 Aug 3

Saquinavir Main Page Main New/Newsworthy  Home Page

Saquinavir Journal Citations