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Identification
NameSaquinavir
Accession NumberDB01232  (APRD00623)
TypeSmall Molecule
GroupsApproved, Investigational
Description

An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
Saquinavir MesylateNot AvailableNot Available
SQVNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Invirasetablet, film coated500 mgoralGenentech, Inc.2004-12-17Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Invirasecapsule200 mgoralGenentech, Inc.1995-12-06Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Invirasecapsule200 mgoralREMEDYREPACK INC.2013-05-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Invirasetablet, film coated500 mgoralState of Florida DOH Central Pharmacy2009-07-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Invirasetablet500 mgoralHoffmann La Roche LimitedNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
FortovaseNot Available
ROCNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number127779-20-8
WeightAverage: 670.8408
Monoisotopic: 670.38426874
Chemical FormulaC38H50N6O5
InChI KeyQWAXKHKRTORLEM-LINFGICFSA-N
InChI
InChI=1S/C38H50N6O5/c1-38(2,3)43-37(49)32-20-26-14-7-8-15-27(26)22-44(32)23-33(45)30(19-24-11-5-4-6-12-24)41-36(48)31(21-34(39)46)42-35(47)29-18-17-25-13-9-10-16-28(25)40-29/h4-6,9-13,16-18,26-27,30-33,45H,7-8,14-15,19-23H2,1-3H3,(H2,39,46)(H,41,48)(H,42,47)(H,43,49)/t26?,27?,30-,31-,32-,33+/m0/s1
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
SMILES
CC(C)(C)NC(=O)[C@@H]1CC2CCCCC2CN1C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(N)=O)NC(=O)C1=NC2=CC=CC=C2C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentN-acyl-alpha amino acids and derivatives
Alternative Parents
Substituents
  • Quinoline-2-carboxamide
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid amide
  • Phenylbutylamine
  • Quinoline
  • Amphetamine or derivatives
  • Pyridine carboxylic acid or derivatives
  • Piperidinecarboxylic acid
  • Piperidinecarboxamide
  • 2-piperidinecarboxamide
  • Aralkylamine
  • Fatty acyl
  • Benzenoid
  • Pyridine
  • Piperidine
  • N-acyl-amine
  • Fatty amide
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Primary carboxylic acid amide
  • Carboxamide group
  • 1,2-aminoalcohol
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of HIV-1 with advanced immunodeficiency together with antiretroviral nucleoside analogues.
PharmacodynamicsSaquinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Saquinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.
Mechanism of actionSaquinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
AbsorptionAbsolute bioavailability averages 4%
Volume of distribution
  • 700 L
Protein binding98%
Metabolism

Hepatic

SubstrateEnzymesProduct
Saquinavir
M2 di-hydroxylated metaboliteDetails
Route of eliminationIn vitro studies using human liver microsomes have shown that the metabolism of saquinavir is cytochrome P450 mediated with the specific isoenzyme, CYP3A4, responsible for more than 90% of the hepatic metabolism. Only 1% of saquinavir is excreted in the urine, so the impact of renal impairment on saquinavir elimination should be minimal.
Half lifeNot Available
Clearance
  • 1.14 L/h/kg [Healthy volunteers receiving IV doses of 6, 36, and 72 mg]
ToxicityProbably experience pain in the throat
Affected organisms
  • Human Immunodeficiency Virus
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7774
Blood Brain Barrier-0.9949
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.9048
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.5195
Renal organic cation transporterNon-inhibitor0.8612
CYP450 2C9 substrateNon-substrate0.8593
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.7406
CYP450 1A2 substrateNon-inhibitor0.8729
CYP450 2C9 substrateNon-inhibitor0.7442
CYP450 2D6 substrateNon-inhibitor0.8536
CYP450 2C19 substrateNon-inhibitor0.7124
CYP450 3A4 substrateInhibitor0.5219
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9053
Ames testNon AMES toxic0.8489
CarcinogenicityNon-carcinogens0.865
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6007 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9687
hERG inhibition (predictor II)Inhibitor0.8153
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Capsuleoral200 mg
Tabletoral500 mg
Tablet, film coatedoral500 mg
Prices
Unit descriptionCostUnit
Invirase 500 mg tablet8.72USD tablet
Invirase 200 mg capsule3.87USD capsule
Fortovase 200 mg capsule1.46USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada20304331997-10-212010-11-21
Canada22241252004-09-282016-06-04
United States51964381993-11-192010-11-19
United States63527171999-11-162019-11-16
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point349.84 °CNot Available
water solubilityInsolubleNot Available
logP3.8Not Available
Caco2 permeability-6.26ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.00247 mg/mLALOGPS
logP4.04ALOGPS
logP3.16ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)13.61ChemAxon
pKa (Strongest Basic)8.47ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area166.75 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity186.67 m3·mol-1ChemAxon
Polarizability73.83 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US5196438
General Reference
  1. Forestier F, de Renty P, Peytavin G, Dohin E, Farinotti R, Mandelbrot L: Maternal-fetal transfer of saquinavir studied in the ex vivo placental perfusion model. Am J Obstet Gynecol. 2001 Jul;185(1):178-81. Pubmed
External Links
ATC CodesJ05AE01
AHFS Codes
  • 08:18.08.08
PDB Entries
FDA labelDownload (362 KB)
MSDSDownload (15.8 KB)
Interactions
Drug Interactions
Drug
AbacavirProtease Inhibitors may decrease the serum concentration of Abacavir.
AcetohexamideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
ado-trastuzumab emtansineCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine. Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic DM1 component.
AfatinibP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib.
AlfuzosinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin.
AlmotriptanCYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan.
AlogliptinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
AlosetronCYP3A4 Inhibitors (Strong) may increase the serum concentration of Alosetron.
AlprazolamProtease Inhibitors may increase the serum concentration of ALPRAZolam.
AmiodaroneMay enhance the QTc-prolonging effect of Amiodarone. Saquinavir may increase the serum concentration of Amiodarone.
ApixabanCYP3A4 Inhibitors (Strong) may increase the serum concentration of Apixaban.
AripiprazoleCYP3A4 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole.
AstemizoleCYP3A4 Inhibitors (Strong) may increase the serum concentration of Astemizole.
AtorvastatinProtease Inhibitors may increase the serum concentration of AtorvaSTATin.
AvanafilCYP3A4 Inhibitors (Strong) may increase the serum concentration of Avanafil.
AxitinibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Axitinib.
BatimastatMay increase the serum concentration of other Protease Inhibitors.
BedaquilineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Bedaquiline.
BoceprevirMay decrease the serum concentration of Protease Inhibitors. Protease Inhibitors may decrease the serum concentration of Boceprevir.
BortezomibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Bortezomib.
BosentanBosentan may decrease the serum concentration of Saquinavir. Saquinavir may increase the serum concentration of Bosentan.
BosutinibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Bosutinib.
Brentuximab vedotinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased.
BrinzolamideCYP3A4 Inhibitors (Strong) may increase the serum concentration of Brinzolamide.
CabazitaxelCYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabazitaxel.
CabozantinibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Cabozantinib.
CanagliflozinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
CarbamazepineMay increase the metabolism of Protease Inhibitors. Protease Inhibitors may decrease the metabolism of CarBAMazepine.
ChlorpropamideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
CilostazolCYP3A4 Inhibitors (Strong) may increase the serum concentration of Cilostazol.
CimetidineH2-Antagonists may increase the serum concentration of Saquinavir.
CisaprideProtease Inhibitors may increase the serum concentration of Cisapride. This may result in QTc prolongation and malignant cardiac arrhythmias.
ClarithromycinProtease Inhibitors may diminish the therapeutic effect of Clarithromycin. Specifically, certain protease inhibitors may decrease formation of the active 14-hydroxy-clarithromycin metabolite, which may negatively impact clarithromycin effectiveness vs. H. influenzae and other non-MAC infections. Clarithromycin may increase the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Clarithromycin. Clarithromycin dose adjustment in renally impaired patients may be needed.
ClorazepateSaquinavir may increase the serum concentration of Clorazepate.
ColchicineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine.
ConivaptanCYP3A4 Inhibitors (Strong) may increase the serum concentration of Conivaptan.
CrizotinibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Crizotinib.
CyclophosphamideProtease Inhibitors may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, the incidences of neutropenia, infection, and mucositis may be increased.
Dabigatran etexilateP-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate.
DabrafenibMay decrease the serum concentration of CYP3A4 Substrates.
DapoxetineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Dapoxetine.
DarunavirSaquinavir may decrease the serum concentration of Darunavir.
DasatinibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Dasatinib.
DeferasiroxMay decrease the serum concentration of CYP3A4 Substrates.
DelavirdineMay increase the serum concentration of Protease Inhibitors. Protease Inhibitors may decrease the serum concentration of Delavirdine.
DesogestrelMay decrease the serum concentration of Contraceptives (Progestins).
DiazepamMay increase the serum concentration of Diazepam.
DigoxinProtease Inhibitors may increase the serum concentration of Digoxin. Increased serum concentrations of digoxin may increase risk of AV nodal blockade.
DofetilideMay enhance the arrhythmogenic effect of Dofetilide. Saquinavir may increase the serum concentration of Dofetilide.
DomperidoneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Domperidone.
DronabinolCYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronabinol.
DronedaroneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone.
DrospirenoneMay decrease the serum concentration of Contraceptives (Progestins).
DutasterideCYP3A4 Inhibitors (Strong) may increase the serum concentration of Dutasteride.
EfavirenzSaquinavir may enhance the adverse/toxic effect of Efavirenz. Efavirenz may decrease the serum concentration of Saquinavir.
EnfuvirtideMay increase the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Enfuvirtide.
EplerenoneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone.
ErlotinibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Erlotinib.
EsomeprazoleProton Pump Inhibitors may increase the serum concentration of Saquinavir.
EthynodiolMay decrease the serum concentration of Contraceptives (Progestins).
EtonogestrelMay decrease the serum concentration of Contraceptives (Progestins).
EtravirineMay increase the serum concentration of Protease Inhibitors. This effect is anticipated with nelfinavir. Protease Inhibitors may decrease the serum concentration of Etravirine. This effect is anticipated with darunavir, saquinavir, and lopinavir (with low-dose ritonavir).
EverolimusCYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus.
FamotidineH2-Antagonists may increase the serum concentration of Saquinavir.
FentanylCYP3A4 Inhibitors (Strong) may increase the serum concentration of FentaNYL.
FesoterodineCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine.
FlecainideMay enhance the arrhythmogenic effect of Flecainide. Saquinavir may increase the serum concentration of Flecainide.
FlurazepamMay increase the serum concentration of Flurazepam.
GliclazideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
GlimepirideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
GliquidoneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
GlyburideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
GuanfacineCYP3A4 Inhibitors (Strong) may increase the serum concentration of GuanFACINE.
HalofantrineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Halofantrine.
HydrocodoneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Hydrocodone.
IfosfamideCYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide.
ImatinibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Imatinib.
Insulin AspartHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Insulin DetemirHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Insulin GlargineHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Insulin GlulisineHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Insulin LisproHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Insulin RegularHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Insulin, isophaneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
IrinotecanCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan.
IsoflurophateMay increase the serum concentration of other Protease Inhibitors.
ItraconazoleItraconazole may increase the serum concentration of Saquinavir. Saquinavir may increase the serum concentration of Itraconazole.
IvacaftorCYP3A4 Inhibitors (Strong) may increase the serum concentration of Ivacaftor.
IxabepiloneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone.
LacosamideCYP3A4 Inhibitors (Strong) may increase the serum concentration of Lacosamide.
LansoprazoleProton Pump Inhibitors may increase the serum concentration of Saquinavir.
LapatinibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Lapatinib.
LedipasvirP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ledipasvir.
LercanidipineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Lercanidipine.
LevobupivacaineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine.
LevomilnacipranCYP3A4 Inhibitors (Strong) may increase the serum concentration of Levomilnacipran.
LevonorgestrelMay decrease the serum concentration of Contraceptives (Progestins).
LinagliptinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
LomitapideCYP3A4 Inhibitors (Strong) may increase the serum concentration of Lomitapide.
LopinavirSaquinavir may enhance the QTc-prolonging effect of Lopinavir.
LovastatinProtease Inhibitors may increase the serum concentration of Lovastatin.
LurasidoneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone.
MACITENTANCYP3A4 Inhibitors (Strong) may increase the serum concentration of Macitentan.
MaravirocCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
Medroxyprogesterone AcetateMay decrease the serum concentration of Contraceptives (Progestins).
MestranolMay decrease the serum concentration of Contraceptives (Progestins).
MetforminHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
MethadoneMethadone may enhance the QTc-prolonging effect of Saquinavir. Saquinavir may decrease the serum concentration of Methadone.
MethylprednisoloneCYP3A4 Inhibitors (Strong) may increase the serum concentration of MethylPREDNISolone.
MidazolamProtease Inhibitors may increase the serum concentration of Midazolam.
MifepristoneMay enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents.
MitotaneMay decrease the serum concentration of CYP3A4 Substrates.
NefazodoneProtease Inhibitors may increase the serum concentration of Nefazodone.
NevirapineNevirapine may decrease the serum concentration of Saquinavir.
NilotinibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib.
NisoldipineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine.
NizatidineH2-Antagonists may increase the serum concentration of Saquinavir.
NorelgestrominMay decrease the serum concentration of Contraceptives (Progestins).
NorethindroneMay decrease the serum concentration of Contraceptives (Progestins).
NorgestimateMay decrease the serum concentration of Contraceptives (Progestins).
OmeprazoleProton Pump Inhibitors may increase the serum concentration of Saquinavir.
OspemifeneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Ospemifene.
OxybutyninCYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxybutynin.
OxycodoneCYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased.
PanobinostatCYP3A4 Inhibitors (Strong) may increase the serum concentration of Panobinostat.
PantoprazoleProton Pump Inhibitors may increase the serum concentration of Saquinavir.
ParicalcitolCYP3A4 Inhibitors (Strong) may increase the serum concentration of Paricalcitol.
PazopanibP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib.
PimecrolimusCYP3A4 Inhibitors (Strong) may decrease the metabolism of Pimecrolimus.
PimozideProtease Inhibitors may increase the serum concentration of Pimozide.
PonatinibCYP3A4 Inhibitors (Strong) may increase the serum concentration of PONATinib.
PranlukastCYP3A4 Inhibitors (Strong) may increase the serum concentration of Pranlukast.
PrasugrelCYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Prasugrel.
PravastatinMay decrease the serum concentration of Pravastatin. This effect has only been demonstrated with saquinavir/ritonavir. The individual contributions of saquinavir and ritonavir are unknown.
PrednisoneCYP3A4 Inhibitors (Strong) may increase the serum concentration of PredniSONE.
PropafenoneMay enhance the arrhythmogenic effect of Propafenone. Saquinavir may increase the serum concentration of Propafenone.
prucaloprideP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride.
QuinidineMay enhance the QTc-prolonging effect of QuiNIDine. Saquinavir may increase the serum concentration of QuiNIDine.
RabeprazoleProton Pump Inhibitors may increase the serum concentration of Saquinavir.
RanitidineH2-Antagonists may increase the serum concentration of Saquinavir.
RanolazineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine.
RegorafenibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Regorafenib.
RepaglinideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
RetapamulinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Retapamulin.
RifabutinSaquinavir may increase serum concentrations of the active metabolite(s) of Rifabutin. Rifabutin may decrease the serum concentration of Saquinavir. Saquinavir may increase the serum concentration of Rifabutin.
RifampicinRifampin may enhance the adverse/toxic effect of Saquinavir. Specifically, the risk of hepatocellular toxicity may be increased. Rifampin may decrease the serum concentration of Saquinavir.
RifaximinP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rifaximin.
RilpivirineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Rilpivirine.
RiociguatProtease Inhibitors may increase the serum concentration of Riociguat.
RivaroxabanCYP3A4 Inhibitors (Strong) may increase the serum concentration of Rivaroxaban. For clarithromycin, refer to more specific clarithromycin-rivaroxaban monograph recommendations.
RosuvastatinProtease Inhibitors may increase the serum concentration of Rosuvastatin.
RuxolitinibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Ruxolitinib.
SalmeterolCYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol.
SaxagliptinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
SildenafilProtease Inhibitors may increase the serum concentration of Sildenafil.
SilodosinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Silodosin.
SiltuximabMay decrease the serum concentration of CYP3A4 Substrates.
SimeprevirMay increase the serum concentration of other Protease Inhibitors.
SimvastatinProtease Inhibitors may increase the serum concentration of Simvastatin.
SuvorexantCYP3A4 Inhibitors (Strong) may increase the serum concentration of Suvorexant.
TadalafilCYP3A4 Inhibitors (Strong) may increase the serum concentration of Tadalafil.
TamsulosinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Tamsulosin.
TemsirolimusProtease Inhibitors may enhance the adverse/toxic effect of Temsirolimus. Levels of sirolimus, the active metabolite, may be increased, likely due to inhibition of CYP-mediated metabolism.
TerfenadineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Terfenadine.
TicagrelorCYP3A4 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor.
TipranavirMay decrease the serum concentration of Protease Inhibitors.
TocilizumabMay decrease the serum concentration of CYP3A4 Substrates.
TofacitinibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Tofacitinib.
TolbutamideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
TolterodineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolterodine.
TolvaptanCYP3A4 Inhibitors (Strong) may increase the serum concentration of Tolvaptan.
TopotecanP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan.
ToremifeneCYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect of Toremifene. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene.
TrabectedinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Trabectedin.
TrazodoneSaquinavir may enhance the QTc-prolonging effect of TraZODone. Saquinavir may increase the serum concentration of TraZODone.
TriazolamProtease Inhibitors may increase the serum concentration of Triazolam.
UlipristalCYP3A4 Inhibitors (Strong) may increase the serum concentration of Ulipristal.
VardenafilCYP3A4 Inhibitors (Strong) may increase the serum concentration of Vardenafil.
VemurafenibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Vemurafenib.
VilazodoneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Vilazodone.
VildagliptinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
VorapaxarCYP3A4 Inhibitors (Strong) may increase the serum concentration of Vorapaxar.
WarfarinSaquinavir may increase the serum concentration of Warfarin.
ZidovudineProtease Inhibitors may decrease the serum concentration of Zidovudine.
ZopicloneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Zopiclone.
Food Interactions
  • Take after a full meal.

Targets

1. Protease

Kind: protein

Organism: Human immunodeficiency virus 1

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
HIV-1 Protease Q72874 Details

References:

  1. Wittayanarakul K, Hannongbua S, Feig M: Accurate prediction of protonation state as a prerequisite for reliable MM-PBSA binding free energy calculations of HIV-1 protease inhibitors. J Comput Chem. 2007 Sep 11;. Pubmed
  2. Dandache S, Sevigny G, Yelle J, Stranix BR, Parkin N, Schapiro JM, Wainberg MA, Wu JJ: In Vitro Antiviral Activity and Cross-Resistance Profile of PL-100, a Next Generation Protease Inhibitor of Human Immunodeficiency Virus Type 1. Antimicrob Agents Chemother. 2007 Jul 16;. Pubmed
  3. Dandache S, Coburn CA, Oliveira M, Allison TJ, Holloway MK, Wu JJ, Stranix BR, Panchal C, Wainberg MA, Vacca JP: PL-100, a novel HIV-1 protease inhibitor displaying a high genetic barrier to resistance: an in vitro selection study. J Med Virol. 2008 Dec;80(12):2053-63. Pubmed
  4. Rhee SY, Taylor J, Fessel WJ, Kaufman D, Towner W, Troia P, Ruane P, Hellinger J, Shirvani V, Zolopa A, Shafer RW: HIV-1 protease mutations and protease inhibitor cross-resistance. Antimicrob Agents Chemother. 2010 Oct;54(10):4253-61. Epub 2010 Jul 26. Pubmed
  5. Alcaro S, Artese A, Ceccherini-Silberstein F, Ortuso F, Perno CF, Sing T, Svicher V: Molecular dynamics and free energy studies on the wild-type and mutated HIV-1 protease complexed with four approved drugs: mechanism of binding and drug resistance. J Chem Inf Model. 2009 Jul;49(7):1751-61. Pubmed
  6. Vella S, Lazzarin A, Carosi G, Sinicco A, Armignacco O, Angarano G, Andreoni M, Tambussi G, Chiodera A, Floridia M, Scaccabarozzi S, Facey K, Duncan I, Boudes P, Bragman K: A randomized controlled trial of a protease inhibitor (saquinavir) in combination with zidovudine in previously untreated patients with advanced HIV infection. Antivir Ther. 1996 Aug;1(3):129-40. Pubmed
  7. Hoetelmans RM, Meenhorst PL, Mulder JW, Burger DM, Koks CH, Beijnen JH: Clinical pharmacology of HIV protease inhibitors: focus on saquinavir, indinavir, and ritonavir. Pharm World Sci. 1997 Aug;19(4):159-75. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  4. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. Pubmed

2. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Cholesterol side-chain cleavage enzyme, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cholesterol side-chain cleavage enzyme, mitochondrial P05108 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Carriers

1. Alpha-1-acid glycoprotein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Alpha-1-acid glycoprotein 1 P02763 Details

References:

  1. Holladay JW, Dewey MJ, Michniak BB, Wiltshire H, Halberg DL, Weigl P, Liang Z, Halifax K, Lindup WE, Back DJ: Elevated alpha-1-acid glycoprotein reduces the volume of distribution and systemic clearance of saquinavir. Drug Metab Dispos. 2001 Mar;29(3):299-303. Pubmed

2. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Holladay JW, Dewey MJ, Michniak BB, Wiltshire H, Halberg DL, Weigl P, Liang Z, Halifax K, Lindup WE, Back DJ: Elevated alpha-1-acid glycoprotein reduces the volume of distribution and systemic clearance of saquinavir. Drug Metab Dispos. 2001 Mar;29(3):299-303. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Perloff MD, von Moltke LL, Fahey JM, Daily JP, Greenblatt DJ: Induction of P-glycoprotein expression by HIV protease inhibitors in cell culture. AIDS. 2000 Jun 16;14(9):1287-9. Pubmed
  2. Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR, Kim RB: Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos. 2000 Jun;28(6):655-60. Pubmed
  3. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. Pubmed
  4. Kim AE, Dintaman JM, Waddell DS, Silverman JA: Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein. J Pharmacol Exp Ther. 1998 Sep;286(3):1439-45. Pubmed
  5. Huisman MT, Smit JW, Wiltshire HR, Hoetelmans RM, Beijnen JH, Schinkel AH: P-glycoprotein limits oral availability, brain, and fetal penetration of saquinavir even with high doses of ritonavir. Mol Pharmacol. 2001 Apr;59(4):806-13. Pubmed
  6. Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. Pubmed
  7. Eagling VA, Profit L, Back DJ: Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components. Br J Clin Pharmacol. 1999 Oct;48(4):543-52. Pubmed
  8. Collett A, Tanianis-Hughes J, Hallifax D, Warhurst G: Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo. Pharm Res. 2004 May;21(5):819-26. Pubmed

2. Solute carrier family 22 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 1 O15245 Details

References:

  1. Zhang L, Gorset W, Washington CB, Blaschke TF, Kroetz DL, Giacomini KM: Interactions of HIV protease inhibitors with a human organic cation transporter in a mammalian expression system. Drug Metab Dispos. 2000 Mar;28(3):329-34. Pubmed

3. Solute carrier organic anion transporter family member 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1A2 P46721 Details

References:

  1. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. Pubmed

4. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

References:

  1. Gupta A, Zhang Y, Unadkat JD, Mao Q: HIV protease inhibitors are inhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther. 2004 Jul;310(1):334-41. Epub 2004 Mar 8. Pubmed
  2. Janneh O, Owen A, Chandler B, Hartkoorn RC, Hart CA, Bray PG, Ward SA, Back DJ, Khoo SH: Modulation of the intracellular accumulation of saquinavir in peripheral blood mononuclear cells by inhibitors of MRP1, MRP2, P-gp and BCRP. AIDS. 2005 Dec 2;19(18):2097-102. Pubmed

5. Solute carrier organic anion transporter family member 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

References:

  1. Tirona RG, Leake BF, Wolkoff AW, Kim RB: Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther. 2003 Jan;304(1):223-8. Pubmed

6. Multidrug resistance-associated protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance-associated protein 1 P33527 Details

References:

  1. Williams GC, Liu A, Knipp G, Sinko PJ: Direct evidence that saquinavir is transported by multidrug resistance-associated protein (MRP1) and canalicular multispecific organic anion transporter (MRP2). Antimicrob Agents Chemother. 2002 Nov;46(11):3456-62. Pubmed

7. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

References:

  1. Williams GC, Liu A, Knipp G, Sinko PJ: Direct evidence that saquinavir is transported by multidrug resistance-associated protein (MRP1) and canalicular multispecific organic anion transporter (MRP2). Antimicrob Agents Chemother. 2002 Nov;46(11):3456-62. Pubmed
  2. Huisman MT, Smit JW, Crommentuyn KM, Zelcer N, Wiltshire HR, Beijnen JH, Schinkel AH: Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs. AIDS. 2002 Nov 22;16(17):2295-301. Pubmed
  3. Zelcer N, Huisman MT, Reid G, Wielinga P, Breedveld P, Kuil A, Knipscheer P, Schellens JH, Schinkel AH, Borst P: Evidence for two interacting ligand binding sites in human multidrug resistance protein 2 (ATP binding cassette C2). J Biol Chem. 2003 Jun 27;278(26):23538-44. Epub 2003 Apr 17. Pubmed
  4. Honda Y, Ushigome F, Koyabu N, Morimoto S, Shoyama Y, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux. Br J Pharmacol. 2004 Dec;143(7):856-64. Epub 2004 Oct 25. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:25