Identification

Name
Ritonavir
Accession Number
DB00503
Description

Ritonavir is an HIV protease inhibitor that interferes with the reproductive cycle of HIV. Although it was initially developed as an independent antiviral agent, it has been shown to possess advantageous properties in combination regimens with low-dose ritonavir and other protease inhibitors. It is now more commonly used as a booster of other protease inhibitors and is available in both liquid formulation and as capsules.

While ritonavir is not an active antiviral agent against hepatitis C virus (HCV) infection, it is added in combination therapies indicated for treatment of HCV infections as a booster. Ritonavir is a potent CYP3A inhibitor that increases peak and trough plasma drug concentrations of other protease inhibitors such as Paritaprevir and overall drug exposure. American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) guidelines recommend ritonavir-boosted combination therapies as a first-line therapy for HCV Genotype 1a/b and 4 treatment-naïve patients with or without cirrhosis.

Ritonavir is found in a fixed-dose combination product with Ombitasvir, Dasabuvir, and Paritaprevir as the FDA-approved product Viekira Pak. First approved in December 2014, Viekira Pak is indicated for the treatment of HCV genotype 1b without cirrhosis or with compensated cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis.

Ritonavir is also available as a fixed-dose combination product with Ombitasvir and Paritaprevir as the FDA- and Health Canada-approved product Technivie. First approved in July 2015, Technivie is indicated in combination with Ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis.

In Canada, ritonavir is also available as a fixed-dose combination product with Ombitasvir, Dasabuvir, and Paritaprevir as the Health Canada-approved, commercially available product Holkira Pak. First approved in January 2015, Holkira Pak is indicated for the treatment of HCV genotype 1b with or without cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a with or without cirrhosis. Inclusion of ritonavir can can select for HIV-1 protease inhibitor resistance-associated substitutions. Any HCV/HIV-1 co-infected patients treated with ritonavir-containing combination therapies should also be on a suppressive antiretroviral drug regimen to reduce the risk of HIV-1 protease inhibitor drug resistance.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 720.944
Monoisotopic: 720.312760056
Chemical Formula
C37H48N6O5S2
Synonyms
  • Ritonavir
  • Ritonavirum
External IDs
  • A-84538
  • Abbott 84538
  • ABBOTT-84538
  • ABT 538
  • ABT-538
  • DRG-0244
  • NSC-693184
  • TMC 114r

Pharmacology

Indication

Indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Ritonavir 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. Ritonavir 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. Modern protease inhibitors require the use of low-dose ritonavir to boost pharmacokinetic exposure through inhibition of metabolism via the cytochrome P450 3A4 enzyme pathway.

Mechanism of action

Ritonavic inhibits the HIV viral proteinase enzyme that normally cleaves the structural and replicative proteins that arise from major HIV genes, such as gag and pol. Gag encodes proteins involved in the core and the nucleocapsid, while pol encodes the the HIV reverse transcriptase, ribonuclease H, integrase, and protease 1. The pol-encoded proteins are initially translated in the form of a larger precursoe polypeptide, gag-pol, and needs to be cleaved by HIV protease to form other complement proteins 1. Ritonavir prevents the cleavage of the gag-pol polyprotein, which results in noninfectious, immature viral particles. Ritonavir is a potent inhibitor of cytochrome P450 CYP3A4 isoenzyme present both in the intestinal tract and liver 1. It is a type II ligand that perfectly fits into the CYP3A4 active site cavity and irreversibly binds to the heme iron via the thiazole nitrogen, which decreases the redox potential of the protein and precludes its reduction with the redox partner, cytochrome P450 reductase 3. Ritonavir may also play a role in limiting cellular transport and efflux of other protease inhibitors via the P-glycoprotein and MRP efflux channels 1.

TargetActionsOrganism
AHuman immunodeficiency virus type 1 protease
inhibitor
Human immunodeficiency virus 1
UNuclear receptor subfamily 1 group I member 2
activator
Humans
Absorption

The absolute bioavailability of ritonavir has not been determined.7 Following oral administration, peak concentrations are reached after approximately 2 hours and 4 hours (Tmax) after dosing under fasting and non-fasting conditions, respectively.7 It should be noted that ritonavir capsules and tablets are not considered bioequivalent.7

Volume of distribution

The estimated volume of distribution of ritonavir is 0.41 ± 0.25 L/kg.7

Protein binding

Ritonavir is highly protein-bound in plasma (~98-99%), primarily to albumin and alpha-1 acid glycoprotein over the standard concentration range.7

Metabolism

Ritonavir circulates in the plasma predominantly as unchanged drug. Five metabolites have been identified.7 The isopropylthiazole oxidation metabolite (M-2) is the major metabolite in low plasma concentrations and retains similar antiviral activity to unchanged ritonavir. The cytochrome P450 enzymes CYP3A and CYP2D6 are the enzymes primarily involved in the metabolism of ritonavir.7

Hover over products below to view reaction partners

Route of elimination

Ritonavir is primarily eliminated in the feces.7 Following oral administration of a single 600mg dose of radiolabeled ritonavir, approximately 11.3 ± 2.8% of the dose was excreted into the urine, of which 3.5 ± 1.8% was unchanged parent drug.7 The same study found that 86.4 ± 2.9% of the dose was excreted in the feces, of which 33.8 ± 10.8% was unchanged parent drug.7

Half-life

The approximate half-life of ritonavir is 3-5 hours.7

Clearance

The apparent oral clearance at steady-state is 8.8 ± 3.2 L/h.7 Renal clearance is minimal and estimated to be <0.1 L/h.7

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Human experience of acute overdose with ritonavir is limited. One patient in clinical trials took ritonavir 1500 mg/day for two days. The patient reported paresthesias which resolved after the dose was decreased. A post-marketing case of renal failure with eosinophilia has been reported with ritonavir overdose. The approximate lethal dose was found to be greater than 20 times the related human dose in rats and 10 times the related human dose in mice. Oral LD value in rats is >2500 mg/kg. Adverse effects of ritonavir may arise from drug-drug interactions. Other effects include hepatotoxicity, pancreatitis, and allergic reactions/hypersensitivity.

Affected organisms
  • Human Immunodeficiency Virus
  • SARS-CoV-2
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Ritonavir.
AbametapirThe serum concentration of Ritonavir can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Ritonavir can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Ritonavir.
AbirateroneThe serum concentration of Abiraterone can be increased when it is combined with Ritonavir.
AcalabrutinibThe metabolism of Ritonavir can be decreased when combined with Acalabrutinib.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Ritonavir.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Ritonavir.
AcenocoumarolThe serum concentration of Acenocoumarol can be decreased when it is combined with Ritonavir.
AcetaminophenThe serum concentration of Acetaminophen can be increased when it is combined with Ritonavir.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid St. John's Wort. Co-administration may reduce serum concentrations of ritonavir and interfere with virologic efficacy.

Products

International/Other Brands
Busvir (Conifarma) / Empetus (Emcure) / Normune (Grey Inversiones)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NorvirTablet, film coated100 mg/1OralA-S Medication Solutions2010-05-06Not applicableUS flag
NorvirSolution80 mg/1mLOralAbbVie Inc.2010-05-06Not applicableUS flag
NorvirTablet100 mgOralAbbvie2010-12-17Not applicableCanada flag
NorvirTablet, film coated100 mg/1OralDoh Central Pharmacy2018-01-09Not applicableUS flag
NorvirTablet, film coated100 mg/1OralREMEDYREPACK INC.2015-08-062018-02-06US flag
NorvirCapsule100 mg/1OralPhysicians Total Care, Inc.2003-07-142007-12-10US flag
NorvirTablet, film coated100 mg/1OralAbbVie Inc.2010-05-06Not applicableUS flag
NorvirSolution80 mgOralAbbvie1996-09-252019-03-31Canada flag
NorvirCapsule100 mg/1OralAbbVie Inc.2010-05-06Not applicableUS flag
NorvirPowder100 mg/1OralAbbVie Inc.2017-06-07Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RitonavirTablet, film coated100 mg/1OralAmerican Health Packaging2018-05-012019-10-31US flag
RitonavirTablet, film coated100 mg/1OralAmerican Health Packaging2018-11-30Not applicableUS flag
RitonavirTablet, film coated100 mg/1OralWest-Ward Pharmaceuticals Corp.2018-03-20Not applicableUS flag
RitonavirTablet100 mg/1OralREMEDYREPACK INC.2018-10-112020-05-27US flag
RitonavirTablet100 mg/1OralCamber Pharmaceuticals, Inc.2018-09-17Not applicableUS flag
RitonavirTablet, film coated100 mg/1OralAurobindo Pharma Limited2018-09-17Not applicableUS flag
RitonavirTablet, film coated100 mg/1OralREMEDYREPACK INC.2019-04-09Not applicableUS flag
RitonavirTablet, film coated100 mg/1OralREMEDYREPACK INC.2018-03-292020-05-12US flag
RitonavirTablet, film coated100 mg/1OralZydus Pharmaceuticals USA Inc2018-03-202020-01-10US flag
RitonavirTablet100 mg/1OralAmneal Pharmaceuticals LLC2018-09-21Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Holkira PakRitonavir (50 mg) + Dasabuvir (250 mg) + Ombitasvir (12.5 mg) + Paritaprevir (75 mg)Kit; TabletOralAbbvie2015-01-062018-08-15Canada flag
KaletraRitonavir (25 mg/1) + Lopinavir (100 mg/1)Tablet, film coatedOralAbbVie Inc.2020-04-08Not applicableUS flag
KaletraRitonavir (50 mg/1) + Lopinavir (200 mg/1)Tablet, film coatedOralPD-Rx Pharmaceuticals, Inc.2010-06-18Not applicableUS flag
KaletraRitonavir (50 mg/1) + Lopinavir (200 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2006-04-11Not applicableUS flag
KaletraRitonavir (25 mg) + Lopinavir (100 mg)TabletOralAbbvie2008-08-11Not applicableCanada flag
KaletraRitonavir (50 mg/1) + Lopinavir (200 mg/1)Tablet, film coatedOralRemedy Repack2008-09-052017-01-16US flag
KaletraRitonavir (20 mg/1mL) + Lopinavir (80 mg/1mL)SolutionOralAbbVie Inc.2010-06-18Not applicableUS flag
KaletraRitonavir (50 mg/1) + Lopinavir (200 mg/1)Tablet, film coatedOralCardinal Health2010-06-182016-01-31US flag
KaletraRitonavir (100 mg) + Lopinavir (400 mg)SolutionOralAbbvie2001-03-09Not applicableCanada flag
KaletraRitonavir (50 mg/1) + Lopinavir (200 mg/1)Tablet, film coatedOralDispensing Solutions, Inc.2010-06-18Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
KaletraRitonavir (50 mg/1) + Lopinavir (200 mg/1)TabletOralRemedy Repack2010-09-272013-05-16US flag

Categories

ATC Codes
J05AP53 — Ombitasvir, paritaprevir and ritonavirJ05AR10 — Lopinavir and ritonavirJ05AE03 — RitonavirJ05AR23 — Atazanavir and ritonavirJ05AR26 — Darunavir and ritonavirJ05AP52 — Dasabuvir, ombitasvir, paritaprevir and ritonavir
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as n-carbamoyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an carbamoyl group at its terminal nitrogen atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
N-carbamoyl-alpha amino acids and derivatives
Alternative Parents
Valine and derivatives / Alpha amino acid amides / Amphetamines and derivatives / 2,4-disubstituted thiazoles / N-acyl amines / Carbamate esters / Heteroaromatic compounds / Secondary carboxylic acid amides / Ureas / Secondary alcohols
show 6 more
Substituents
2,4-disubstituted 1,3-thiazole / Alcohol / Alpha-amino acid amide / Amphetamine or derivatives / Aromatic heteromonocyclic compound / Azacycle / Azole / Benzenoid / Carbamic acid ester / Carbonic acid derivative
show 21 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
carbamate ester, ureas, 1,3-thiazole, carboxamide, L-valine derivative (CHEBI:45409)

Chemical Identifiers

UNII
O3J8G9O825
CAS number
155213-67-5
InChI Key
NCDNCNXCDXHOMX-XGKFQTDJSA-N
InChI
InChI=1S/C37H48N6O5S2/c1-24(2)33(42-36(46)43(5)20-29-22-49-35(40-29)25(3)4)34(45)39-28(16-26-12-8-6-9-13-26)18-32(44)31(17-27-14-10-7-11-15-27)41-37(47)48-21-30-19-38-23-50-30/h6-15,19,22-25,28,31-33,44H,16-18,20-21H2,1-5H3,(H,39,45)(H,41,47)(H,42,46)/t28-,31-,32-,33-/m0/s1
IUPAC Name
(1,3-thiazol-5-yl)methyl N-[(2S,3S,5S)-3-hydroxy-5-[(2S)-3-methyl-2-{[methyl({[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl})carbamoyl]amino}butanamido]-1,6-diphenylhexan-2-yl]carbamate
SMILES
CC(C)[[email protected]](NC(=O)N(C)CC1=CSC(=N1)C(C)C)C(=O)N[[email protected]](C[[email protected]](O)[[email protected]](CC1=CC=CC=C1)NC(=O)OCC1=CN=CS1)CC1=CC=CC=C1

References

Synthesis Reference
US5484801
General References
  1. Hull MW, Montaner JS: Ritonavir-boosted protease inhibitors in HIV therapy. Ann Med. 2011 Aug;43(5):375-88. doi: 10.3109/07853890.2011.572905. Epub 2011 Apr 18. [PubMed:21501034]
  2. Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13. [PubMed:25585348]
  3. Sevrioukova IF, Poulos TL: Structure and mechanism of the complex between cytochrome P4503A4 and ritonavir. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18422-7. doi: 10.1073/pnas.1010693107. Epub 2010 Oct 11. [PubMed:20937904]
  4. Rock BM, Hengel SM, Rock DA, Wienkers LC, Kunze KL: Characterization of ritonavir-mediated inactivation of cytochrome P450 3A4. Mol Pharmacol. 2014 Dec;86(6):665-74. doi: 10.1124/mol.114.094862. Epub 2014 Oct 1. [PubMed:25274602]
  5. Tseng A, Hughes CA, Wu J, Seet J, Phillips EJ: Cobicistat Versus Ritonavir: Similar Pharmacokinetic Enhancers But Some Important Differences. Ann Pharmacother. 2017 Nov;51(11):1008-1022. doi: 10.1177/1060028017717018. Epub 2017 Jun 19. [PubMed:28627229]
  6. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
  7. FDA Approved Drug Products: NORVIR (ritonavir) Capsules, Soft Gelatin for Oral use [Link]
  8. FDA Approved Drug Products: Norvir (ritonavir) for oral use [Link]
  9. CaymanChem: Ritonavir MSDS [Link]
Human Metabolome Database
HMDB0014646
KEGG Drug
D00427
KEGG Compound
C07240
PubChem Compound
392622
PubChem Substance
46505050
ChemSpider
347980
BindingDB
520
RxNav
85762
ChEBI
45409
ChEMBL
CHEMBL163
ZINC
ZINC000003944422
Therapeutic Targets Database
DAP000169
PharmGKB
PA451260
PDBe Ligand
RIT
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ritonavir
AHFS Codes
  • 08:18.08.08 — HIV Protease Inhibitors
PDB Entries
1hxw / 1n49 / 1rl8 / 1sh9 / 2b60 / 3ndw / 3ndx / 3nxu / 3prs / 3q70
show 6 more
FDA label
Download (960 KB)
MSDS
Download (26.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
4Active Not RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection / Chronic Kidney Disease (CKD)1
4Active Not RecruitingTreatmentHepatitis C Virus (HCV) Infection1
4CompletedNot AvailableHealthy Volunteers3
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections3
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Proteinuria1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis (TB)1
4CompletedBasic ScienceCardiovascular Heart Disease / Dyslipidemia / Glucose Metabolism Disorders / Human Immunodeficiency Virus (HIV) Infections / Lipodystrophies / Metabolic Diseases1
4CompletedBasic ScienceDrug Drug Interaction (DDI)1
4CompletedBasic ScienceHuman Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
  • Abbott laboratories pharmaceutical products div
  • Abbott laboratories
Packagers
  • Abbott Laboratories Ltd.
  • Atlantic Biologicals Corporation
  • Cardinal Health
  • Catalent Pharma Solutions
  • DHHS Program Support Center Supply Service Center
  • Dispensing Solutions
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Murfreesboro Pharmaceutical Nursing Supply
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
  • Remedy Repack
  • Southwood Pharmaceuticals
Dosage Forms
FormRouteStrength
Tablet, film coatedOral800 mg
Kit; tabletOral
Capsule133 mg
Capsule133.3 mg
CapsuleOral
Capsule, liquid filledOral
TabletOral
TabletOral200 MG
Tablet, film coatedOral
Tablet, film coatedOral200 mg
CapsuleOral133.3 mg
SolutionOral80 mg
Tablet, coatedOral200 mg
Capsule, coatedOral40 mg
GranuleOral
SolutionOral
Capsule100 MG
CapsuleOral100 mg/1
CapsuleOral100 MG
PowderOral100 mg/1
Powder, for suspensionOral100 MG
SolutionOral80 MG/ML
SolutionOral80 mg/1mL
Solution / dropsOral80 mg/1mL
TabletOral100 mg
Tablet, film coatedOral100 mg/1
Tablet, film coated100 mg
CapsuleOral
Tablet
Tablet, coatedOral100 mg
Capsule, coatedOral100 mg
Tablet100 mg
TabletOral100 mg/1
Tablet, film coatedOral100 mg
Capsule, liquid filledOral100 mg
Tablet, film coatedOral12.5 MG
Tablet, coatedOral12.5 mg
TabletOral600 mg
Tablet, coatedOral800 mg
Tablet, coatedOral300 mg
Prices
Unit descriptionCostUnit
Norvir 100 mg softgel cap10.29USD softgel capsule
Norvir 100 mg tablet10.29USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5541206No1996-07-302013-07-30US flag
CA2178632No2006-04-112015-01-03Canada flag
CA2135890No1996-08-272013-12-16Canada flag
US6703403Yes2004-03-092016-12-26US flag
US6037157Yes2000-03-142016-12-26US flag
US6232333Yes2001-05-152018-05-07US flag
US7432294Yes2008-10-072020-11-22US flag
US7141593Yes2006-11-282020-11-22US flag
US5914332Yes1999-06-222016-06-13US flag
US6284767Yes2001-09-042016-08-15US flag
US7364752Yes2008-04-292021-05-10US flag
US8309613Yes2012-11-132025-06-24US flag
US8377952Yes2013-02-192028-04-22US flag
US8691878Yes2014-04-082025-02-25US flag
US8025899Yes2011-09-272028-06-14US flag
US7148359Yes2006-12-122020-01-19US flag
US8470347Yes2013-06-252027-03-17US flag
US8268349Yes2012-09-182025-02-25US flag
US8399015Yes2013-03-192025-02-25US flag
US6458818Yes2002-10-012018-05-07US flag
US6521651Yes2003-02-182018-05-07US flag
US6911214Yes2005-06-282022-05-28US flag
US8501219No2013-08-062021-11-28US flag
US9139536No2015-09-222028-11-09US flag
US8685984No2014-04-012032-09-04US flag
US8466159No2013-06-182032-09-04US flag
US8642538No2014-02-042029-09-10US flag
US8501238No2013-08-062028-09-17US flag
US8680106No2014-03-252032-09-04US flag
US8492386No2013-07-232032-09-04US flag
US8188104No2012-05-292029-05-17US flag
US9006387No2015-04-142030-06-10US flag
US9044480No2015-06-022031-04-10US flag
US8686026No2014-04-012031-06-09US flag
US8420596Yes2013-04-162031-10-10US flag
US8691938No2014-04-082032-04-13US flag
US9629841No2017-04-252033-10-18US flag
US9333204No2016-05-102035-01-02US flag
US9744170No2017-08-292035-01-02US flag
US10105365No2018-10-232035-01-02US flag
US10201584No2019-02-122032-05-17US flag
US10201542No2019-02-122033-10-18US flag
US10201541No2019-02-122032-05-17US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityPractically insolubleFDA Label
logP3.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00126 mg/mLALOGPS
logP4.24ALOGPS
logP5.22ChemAxon
logS-5.8ALOGPS
pKa (Strongest Acidic)13.68ChemAxon
pKa (Strongest Basic)2.84ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area145.78 Å2ChemAxon
Rotatable Bond Count18ChemAxon
Refractivity194.59 m3·mol-1ChemAxon
Polarizability76.23 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.7195
Blood Brain Barrier-0.9717
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.8307
P-glycoprotein inhibitor IInhibitor0.8317
P-glycoprotein inhibitor IINon-inhibitor0.8753
Renal organic cation transporterNon-inhibitor0.9009
CYP450 2C9 substrateNon-substrate0.694
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.5973
CYP450 1A2 substrateNon-inhibitor0.67
CYP450 2C9 inhibitorNon-inhibitor0.6229
CYP450 2D6 inhibitorNon-inhibitor0.8424
CYP450 2C19 inhibitorInhibitor0.5399
CYP450 3A4 inhibitorInhibitor0.5843
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5946
Ames testNon AMES toxic0.7378
CarcinogenicityNon-carcinogens0.8664
BiodegradationNot ready biodegradable0.9633
Rat acute toxicity2.6154 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9774
hERG inhibition (predictor II)Inhibitor0.8457
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available

Targets

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Aspartic-type endopeptidase activity
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q72874
Uniprot Name
Pol polyprotein
Molecular Weight
10778.7 Da
References
  1. Garriga C, Perez-Elias MJ, Delgado R, Ruiz L, Najera R, Pumarola T, Alonso-Socas Mdel M, Garcia-Bujalance S, Menendez-Arias L: Mutational patterns and correlated amino acid substitutions in the HIV-1 protease after virological failure to nelfinavir- and lopinavir/ritonavir-based treatments. J Med Virol. 2007 Nov;79(11):1617-28. [PubMed:17854027]
  2. Das A, Rao DR, Hosur MV: X-ray structure of HIV-1 protease tethered dimer complexed to ritonavir. Protein Pept Lett. 2007;14(6):565-8. [PubMed:17627597]
  3. Wittayanarakul K, Hannongbua S, Feig M: Accurate prediction of protonation state as a prerequisite for reliable MM-PB(GB)SA binding free energy calculations of HIV-1 protease inhibitors. J Comput Chem. 2008 Apr 15;29(5):673-85. [PubMed:17849388]
  4. Markowitz M, Saag M, Powderly WG, Hurley AM, Hsu A, Valdes JM, Henry D, Sattler F, La Marca A, Leonard JM, et al.: A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. N Engl J Med. 1995 Dec 7;333(23):1534-9. [PubMed:7477168]
  5. 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:9297727]
  6. FDA Approved Drug Products: Norvir (ritonavir) for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Activator
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Faucette SR, Wang H, Hamilton GA, Jolley SL, Gilbert D, Lindley C, Yan B, Negishi M, LeCluyse EL: Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. Drug Metab Dispos. 2004 Mar;32(3):348-58. [PubMed:14977870]
  2. Smith CM, Faucette SR, Wang H, LeCluyse EL: Modulation of UDP-glucuronosyltransferase 1A1 in primary human hepatocytes by prototypical inducers. J Biochem Mol Toxicol. 2005;19(2):96-108. [PubMed:15849716]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Sevrioukova IF, Poulos TL: Structure and mechanism of the complex between cytochrome P4503A4 and ritonavir. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18422-7. doi: 10.1073/pnas.1010693107. Epub 2010 Oct 11. [PubMed:20937904]
  2. Drug Interactions & Labeling - FDA [Link]
  3. Flockhart Table of Drug Interactions [Link]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW, Duan SX, Fogelman SM, Daily JP, Harmatz JS, Shader RI: Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir. J Clin Pharmacol. 1998 Feb;38(2):106-11. [PubMed:9549640]
  2. Bremner RM, DeMeester TR: Current management of patients with esophageal motor abnormalities. Adv Surg. 1996;30:349-84. [PubMed:8960344]
  3. Wyen C, Fuhr U, Frank D, Aarnoutse RE, Klaassen T, Lazar A, Seeringer A, Doroshyenko O, Kirchheiner JC, Abdulrazik F, Schmeisser N, Lehmann C, Hein W, Schomig E, Burger DM, Fatkenheuer G, Jetter A: Effect of an antiretroviral regimen containing ritonavir boosted lopinavir on intestinal and hepatic CYP3A, CYP2D6 and P-glycoprotein in HIV-infected patients. Clin Pharmacol Ther. 2008 Jul;84(1):75-82. doi: 10.1038/sj.clpt.6100452. Epub 2008 Jan 9. [PubMed:18183034]
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Foisy MM, Yakiwchuk EM, Hughes CA: Induction effects of ritonavir: implications for drug interactions. Ann Pharmacother. 2008 Jul;42(7):1048-59. doi: 10.1345/aph.1K615. Epub 2008 Jun 24. [PubMed:18577765]
  2. Yeh RF, Gaver VE, Patterson KB, Rezk NL, Baxter-Meheux F, Blake MJ, Eron JJ Jr, Klein CE, Rublein JC, Kashuba AD: Lopinavir/ritonavir induces the hepatic activity of cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP1A2 but inhibits the hepatic and intestinal activity of CYP3A as measured by a phenotyping drug cocktail in healthy volunteers. J Acquir Immune Defic Syndr. 2006 May;42(1):52-60. doi: 10.1097/01.qai.0000219774.20174.64. [PubMed:16639344]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  4. Ritonavir FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Hughes CA, Freitas A, Miedzinski LJ: Interaction between lopinavir/ritonavir and warfarin. CMAJ. 2007 Aug 14;177(4):357-9. doi: 10.1503/cmaj.061284. [PubMed:17698824]
  2. Tseng A, Hughes CA, Wu J, Seet J, Phillips EJ: Cobicistat Versus Ritonavir: Similar Pharmacokinetic Enhancers But Some Important Differences. Ann Pharmacother. 2017 Nov;51(11):1008-1022. doi: 10.1177/1060028017717018. Epub 2017 Jun 19. [PubMed:28627229]
  3. von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW, Duan SX, Fogelman SM, Daily JP, Harmatz JS, Shader RI: Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir. J Clin Pharmacol. 1998 Feb;38(2):106-11. [PubMed:9549640]
  4. Yeh RF, Gaver VE, Patterson KB, Rezk NL, Baxter-Meheux F, Blake MJ, Eron JJ Jr, Klein CE, Rublein JC, Kashuba AD: Lopinavir/ritonavir induces the hepatic activity of cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP1A2 but inhibits the hepatic and intestinal activity of CYP3A as measured by a phenotyping drug cocktail in healthy volunteers. J Acquir Immune Defic Syndr. 2006 May;42(1):52-60. doi: 10.1097/01.qai.0000219774.20174.64. [PubMed:16639344]
  5. Flockhart Table of Drug Interactions [Link]
  6. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Details
5. Cytochrome P450 2B6
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Tanabe M, Hashimoto M, Ono H: Imidazoline I(1) receptor-mediated reduction of muscle rigidity in the reserpine-treated murine model of Parkinson's disease. Eur J Pharmacol. 2008 Jul 28;589(1-3):102-5. doi: 10.1016/j.ejphar.2008.06.013. Epub 2008 Jun 7. [PubMed:18602099]
  2. Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [PubMed:17101742]
  3. Fahmi OA, Shebley M, Palamanda J, Sinz MW, Ramsden D, Einolf HJ, Chen L, Wang H: Evaluation of CYP2B6 Induction and Prediction of Clinical Drug-Drug Interactions: Considerations from the IQ Consortium Induction Working Group-An Industry Perspective. Drug Metab Dispos. 2016 Oct;44(10):1720-30. doi: 10.1124/dmd.116.071076. Epub 2016 Jul 15. [PubMed:27422672]
  4. Lin HL, D'Agostino J, Kenaan C, Calinski D, Hollenberg PF: The effect of ritonavir on human CYP2B6 catalytic activity: heme modification contributes to the mechanism-based inactivation of CYP2B6 and CYP3A4 by ritonavir. Drug Metab Dispos. 2013 Oct;41(10):1813-24. doi: 10.1124/dmd.113.053108. Epub 2013 Jul 25. [PubMed:23886699]
  5. Hesse LM, von Moltke LL, Shader RI, Greenblatt DJ: Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion. Drug Metab Dispos. 2001 Feb;29(2):100-2. [PubMed:11159797]
  6. NORVIR (ritonavir) - FDA Label [Link]
  7. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807]
  2. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
  3. Marzolini C, Gibbons S, Khoo S, Back D: Cobicistat versus ritonavir boosting and differences in the drug-drug interaction profiles with co-medications. J Antimicrob Chemother. 2016 Jul;71(7):1755-8. doi: 10.1093/jac/dkw032. Epub 2016 Mar 5. [PubMed:26945713]
  4. Shebley M, Fu W, Badri P, Bow D, Fischer V: Physiologically Based Pharmacokinetic Modeling Suggests Limited Drug-Drug Interaction Between Clopidogrel and Dasabuvir. Clin Pharmacol Ther. 2017 Oct;102(4):679-687. doi: 10.1002/cpt.689. Epub 2017 Jun 3. [PubMed:28411400]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Vourvahis M, Kashuba AD: Mechanisms of pharmacokinetic and pharmacodynamic drug interactions associated with ritonavir-enhanced tipranavir. Pharmacotherapy. 2007 Jun;27(6):888-909. doi: 10.1592/phco.27.6.888. [PubMed:17542771]
  2. Eagling VA, Back DJ, Barry MG: Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. Br J Clin Pharmacol. 1997 Aug;44(2):190-4. [PubMed:9278209]
  3. Kirby BJ, Collier AC, Kharasch ED, Dixit V, Desai P, Whittington D, Thummel KE, Unadkat JD: Complex drug interactions of HIV protease inhibitors 2: in vivo induction and in vitro to in vivo correlation of induction of cytochrome P450 1A2, 2B6, and 2C9 by ritonavir or nelfinavir. Drug Metab Dispos. 2011 Dec;39(12):2329-37. doi: 10.1124/dmd.111.038646. Epub 2011 Sep 19. [PubMed:21930825]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  5. FDA, ritonavir [File]
Details
8. Cytochrome P450 3A5
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Flockhart Table of Drug Interactions [Link]
Kind
Protein group
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...

Components:
References
  1. Tseng A, Hughes CA, Wu J, Seet J, Phillips EJ: Cobicistat Versus Ritonavir: Similar Pharmacokinetic Enhancers But Some Important Differences. Ann Pharmacother. 2017 Nov;51(11):1008-1022. doi: 10.1177/1060028017717018. Epub 2017 Jun 19. [PubMed:28627229]
  2. Interactions [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Bocedi A, Notaril S, Narciso P, Bolli A, Fasano M, Ascenzi P: Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. [PubMed:15814459]
  2. Bocedi A, Notari S, Menegatti E, Fanali G, Fasano M, Ascenzi P: Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin. FEBS J. 2005 Dec;272(24):6287-96. [PubMed:16336266]
  3. FDA Approved Drug Products: NORVIR (ritonavir) Capsules, Soft Gelatin for Oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. FDA Approved Drug Products: NORVIR (ritonavir) Capsules, Soft Gelatin for Oral use [Link]

Transporters

Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Perloff MD, Von Moltke LL, Marchand JE, Greenblatt DJ: Ritonavir induces P-glycoprotein expression, multidrug resistance-associated protein (MRP1) expression, and drug transporter-mediated activity in a human intestinal cell line. J Pharm Sci. 2001 Nov;90(11):1829-37. doi: 10.1002/jps.1133. [PubMed:11745741]
  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:10820137]
  3. Kumar S, Kwei GY, Poon GK, Iliff SA, Wang Y, Chen Q, Franklin RB, Didolkar V, Wang RW, Yamazaki M, Chiu SH, Lin JH, Pearson PG, Baillie TA: Pharmacokinetics and interactions of a novel antagonist of chemokine receptor 5 (CCR5) with ritonavir in rats and monkeys: role of CYP3A and P-glycoprotein. J Pharmacol Exp Ther. 2003 Mar;304(3):1161-71. [PubMed:12604693]
  4. 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:12699389]
  5. Yamazaki M, Neway WE, Ohe T, Chen I, Rowe JF, Hochman JH, Chiba M, Lin JH: In vitro substrate identification studies for p-glycoprotein-mediated transport: species difference and predictability of in vivo results. J Pharmacol Exp Ther. 2001 Mar;296(3):723-35. [PubMed:11181899]
  6. 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:11259625]
  7. 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:12948019]
  8. Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. [PubMed:11785684]
  9. Corallo CE, Grannell L, Tran H: Postoperative Bleeding After Administration of a Single Dose of Rivaroxaban to a Patient Receiving Antiretroviral Therapy. Drug Saf Case Rep. 2015 Dec;2(1):11. doi: 10.1007/s40800-015-0014-4. [PubMed:27747723]
  10. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Perloff MD, Von Moltke LL, Marchand JE, Greenblatt DJ: Ritonavir induces P-glycoprotein expression, multidrug resistance-associated protein (MRP1) expression, and drug transporter-mediated activity in a human intestinal cell line. J Pharm Sci. 2001 Nov;90(11):1829-37. doi: 10.1002/jps.1133. [PubMed:11745741]
  2. Olson DP, Scadden DT, D'Aquila RT, De Pasquale MP: The protease inhibitor ritonavir inhibits the functional activity of the multidrug resistance related-protein 1 (MRP-1). AIDS. 2002 Sep 6;16(13):1743-7. [PubMed:12218384]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
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:10421612]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Dussault I, Lin M, Hollister K, Wang EH, Synold TW, Forman BM: Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR. J Biol Chem. 2001 Sep 7;276(36):33309-12. Epub 2001 Jul 20. [PubMed:11466304]
  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:12441801]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
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:15007102]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
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:12490595]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Annaert P, Ye ZW, Stieger B, Augustijns P: Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1. Xenobiotica. 2010 Mar;40(3):163-76. doi: 10.3109/00498250903509375. [PubMed:20102298]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2020 01:55

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