Identification

Name
Rilpivirine
Accession Number
DB08864  (DB08592, DB05083)
Type
Small Molecule
Groups
Approved
Description

Rilpivirine is non-nucleoside reverse transcriptase inhibitor (NNRTI) which is used for the treatment of HIV-1 infections in treatment-naive patients.[5] It is a diarylpyrimidine derivative, a class of molecules that resemble pyrimidine nucleotides found in DNA.[6] The internal conformational flexibility of rilpivirine and the plasticity of it interacting binding site gives it a very high potency and an unlikely generation of resistance compared to other NNRTI's.[7] Rilpivirine was developed by Tilbotec, Inc. and FDA approved on May 20, 2011.[10] On November 21, 2017, Rilpivirine, in combination with dolutegravir, was approved as part of the first complete treatment regimen with only two drugs for the treatment of adults with HIV-1 named Juluca.[11]

Structure
Thumb
Synonyms
  • 4-{[4-({4-[(E)-2-cyanovinyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile
External IDs
R 278474 / R-278474 / TMC 278 / TMC-278 / TMC278
Product Ingredients
IngredientUNIICASInChI Key
Rilpivirine Hydrochloride212WAX8KDD700361-47-3KZVVGZKAVZUACK-BJILWQEISA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EdurantTablet25 mgOralJanssen Pharmaceuticals2011-08-31Not applicableCanada
EdurantTablet, film coated25 mg/1OralJanssen, Lp2011-05-20Not applicableUs
EdurantTablet, film coated25 mgOralJanssen Cilag International Nv2011-11-28Not applicableEu
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
CompleraRilpivirine (25 mg) + Emtricitabine (200 mg) + Tenofovir disoproxil fumarate (300 mg)TabletOralGilead Sciences2011-10-20Not applicableCanada
CompleraRilpivirine Hydrochloride (25 mg/1) + Emtricitabine (200 mg/1) + Tenofovir disoproxil fumarate (300 mg/1)Tablet, film coatedOralRemedy Repack2017-08-16Not applicableUs
CompleraRilpivirine Hydrochloride (25 mg/1) + Emtricitabine (200 mg/1) + Tenofovir disoproxil fumarate (300 mg/1)Tablet, film coatedOralGilead Sciences2011-08-10Not applicableUs
CompleraRilpivirine Hydrochloride (25 mg/1) + Emtricitabine (200 mg/1) + Tenofovir disoproxil fumarate (300 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2013-02-01Not applicableUs
CompleraRilpivirine Hydrochloride (25 mg/1) + Emtricitabine (200 mg/1) + Tenofovir disoproxil fumarate (300 mg/1)Tablet, film coatedOralA-S Medication Solutions2011-08-10Not applicableUs
CompleraRilpivirine Hydrochloride (25 mg/1) + Emtricitabine (200 mg/1) + Tenofovir disoproxil fumarate (300 mg/1)Tablet, film coatedOralA-S Medication Solutions2011-08-10Not applicableUs
JulucaRilpivirine Hydrochloride (25 mg/1) + Dolutegravir Sodium (50 mg/1)Tablet, film coatedOralViiV Healthcare Company2017-11-21Not applicableUs
OdefseyRilpivirine Hydrochloride (25 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide (25 mg)Tablet, film coatedOralGilead Sciences Ireland Uc2016-06-21Not applicableEu
OdefseyRilpivirine Hydrochloride (25 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide fumarate (25 mg/1)TabletOralRemedy Repack2017-08-17Not applicableUs
OdefseyRilpivirine Hydrochloride (25 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide fumarate (25 mg/1)TabletOralA-S Medication Solutions2016-03-01Not applicableUs
Categories
UNII
FI96A8X663
CAS number
500287-72-9
Weight
Average: 366.4185
Monoisotopic: 366.159294606
Chemical Formula
C22H18N6
InChI Key
YIBOMRUWOWDFLG-ONEGZZNKSA-N
InChI
InChI=1S/C22H18N6/c1-15-12-18(4-3-10-23)13-16(2)21(15)27-20-9-11-25-22(28-20)26-19-7-5-17(14-24)6-8-19/h3-9,11-13H,1-2H3,(H2,25,26,27,28)/b4-3+
IUPAC Name
4-{[4-({4-[(1E)-2-cyanoeth-1-en-1-yl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile
SMILES
CC1=CC(\C=C\C#N)=CC(C)=C1NC1=CC=NC(NC2=CC=C(C=C2)C#N)=N1

Pharmacology

Indication

Rilpivirine, in combination with other agents, is indicated for the treatment of HIV-1 infections in antiretroviral treatment-naive patients with HIV-1 RNA ≤100,000 copies/mL and CD4+ cell count >200 cells/mm3.[10] The FDA combination therapy approval of rilpivirine and dolutegravir is indicated for adults with HIV-1 infections whose virus is currently suppressed (< 50 copies/ml) on a stable regimen for at least six months, without history of treatment failure and no known substitutions associated to resistance to any of the two components of the therapy.[11]

Associated Conditions
Pharmacodynamics

Ripivirine treatment produces a significant and effective reduction in the viral load based on the study of HIV-1 RNA copies per ml or immunologic changes by the determination of counts of CD4+ and CD8+ cells.[12] The combinantion therapy (ripivirine and dolutegravir) presented the same viral supression found in previous three-drug therapies without integrase strand transfer inhibitor mutations or rilpivirine resistance.[13]

Mechanism of action

Rilpivirine is a non-competitive NNRTI that binds to reverse transcriptase. Its binding results in the blockage of RNA and DNA- dependent DNA polymerase activities, like HIV-1 replication. It does not present activity against human DNA polymerases α, β and γ.[12] Rilpivirine binds to the HIV-1 reverse transcriptase (RT) and its flexible structure around the aromatic rings allows the adaptation to changes in the non-nucleoside RT binding pocket.[8]

TargetActionsOrganism
AReverse transcriptase/RNaseH
inhibitor
Human immunodeficiency virus 1
UNuclear receptor subfamily 1 group I member 2
agonist
Human
Absorption

Absorption of rilpivirine is characterized by a lag time followed by a linear increase in plasma concentration. Under fasting conditions, the Cmax of rilpivirine can be decreased even by 46% while its AUC can be reduced by 43%. When given with a protein-rich drink the Cmax and AUC of rilpivirine is decreased by 50%. Therefore, it is recommended to consume rilpiviridine with a non-protein-rich meal. The average Tmax of various rilpivirine concentrations is 3-4 h.[7] The reported AUC in patients from clinical studies is 2235 ng h/ml.[Label]

Volume of distribution

In VIH-1 patients, the apparent volume of distribution in the central compartment was determined to be 152-173 L.[12]

Protein binding

Rilpivirine is highly protein-bound thus, >99% of its dose can be bound to plasma protein in a concentration-dependent manner.[7] The most important plasma binding proteins is albumin.[Label]

Metabolism

Mainly hepatically metabolized by CYP3A. Because it is highly protein bound, its free plasma concentration is very small thus is unlikely to inhibit cytochrome proteins to a clinically relevant degree despite being an inhibitor of CYP3A4, CYP2C19, and CYP2B6.[1]

Route of elimination

Excreted fecally (85%, 25% as unchanged drug) and urine (6%, < 1% as unchanged drug).[Label]

Half life

Plasma drug elimination is really slow, giving rilpivirine a half-life of 34-55 hours after oral administration.[7]

Clearance

In HIV-1 patients, the apparent oral clearance is estimated to be 10.5-11.8 L/h.[12]

Toxicity

Rilpivirine did not induce chromosomal damage in vivo. It did not show any effect on mating or fertility in animal studies. On the other hand, mice studies have result positive for the formation of hepatocellular neoplasms which can be rodent-specific.[Label]

Affected organisms
  • Humans and other mammals
  • Human Immunodeficiency Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Rilpivirine.
AcetazolamideThe serum concentration of Rilpivirine can be increased when it is combined with Acetazolamide.
Acetyl sulfisoxazoleThe serum concentration of Rilpivirine can be increased when it is combined with Acetyl sulfisoxazole.
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be increased when it is combined with Rilpivirine.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Rilpivirine.
AlclometasoneThe metabolism of Rilpivirine can be decreased when combined with Alclometasone.
AlfentanilThe serum concentration of Alfentanil can be decreased when it is combined with Rilpivirine.
AlfuzosinThe metabolism of Rilpivirine can be decreased when combined with Alfuzosin.
AlimemazineThe risk or severity of QTc prolongation can be increased when Rilpivirine is combined with Alimemazine.
AlphacetylmethadolThe serum concentration of Alphacetylmethadol can be decreased when it is combined with Rilpivirine.
Food Interactions
  • Absorption is increased by 40% if taken with food.
  • Co-administration with St. John's wort decreases levels of rilpivirine by inducing CYP3A4 metabolism. Use is contraindicated.

References

General References
  1. Garvey L, Winston A: Rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor. Expert Opin Investig Drugs. 2009 Jul;18(7):1035-41. doi: 10.1517/13543780903055056. [PubMed:19548857]
  2. Fernandez-Montero JV, Vispo E, Anta L, de Mendoza C, Soriano V: Rilpivirine: a next-generation non-nucleoside analogue for the treatment of HIV infection. Expert Opin Pharmacother. 2012 May;13(7):1007-14. doi: 10.1517/14656566.2012.667802. [PubMed:22519768]
  3. Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [PubMed:23428312]
  4. Zaharatos GJ, Wainberg MA: Update on rilpivirine: a new potent non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV replication. Ann Med. 2013 May;45(3):236-41. doi: 10.3109/07853890.2012.732704. Epub 2012 Nov 17. [PubMed:23157601]
  5. Putcharoen O, Kerr SJ, Ruxrungtham K: An update on clinical utility of rilpivirine in the management of HIV infection in treatment-naive patients. HIV AIDS (Auckl). 2013 Sep 16;5:231-41. doi: 10.2147/HIV.S25712. [PubMed:24068877]
  6. Usach I, Melis V, Peris JE: Non-nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability. J Int AIDS Soc. 2013 Sep 4;16:1-14. doi: 10.7448/IAS.16.1.18567. [PubMed:24008177]
  7. Ford N, Lee J, Andrieux-Meyer I, Calmy A: Safety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings. HIV AIDS (Auckl). 2011;3:35-44. doi: 10.2147/HIV.S14559. Epub 2011 Apr 28. [PubMed:22096405]
  8. Azijn H, Tirry I, Vingerhoets J, de Bethune MP, Kraus G, Boven K, Jochmans D, Van Craenenbroeck E, Picchio G, Rimsky LT: TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother. 2010 Feb;54(2):718-27. doi: 10.1128/AAC.00986-09. Epub 2009 Nov 23. [PubMed:19933797]
  9. Lexicomp 2013 [Link]
  10. J&J News [Link]
  11. FDA News and Events [Link]
  12. Australian report [Link]
  13. J&J News [Link]
External Links
Human Metabolome Database
HMDB0061725
KEGG Drug
D09720
PubChem Compound
6451164
PubChem Substance
175427123
ChemSpider
4953643
BindingDB
222178
ChEBI
68606
ChEMBL
CHEMBL175691
HET
T27
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Rilpivirine
ATC Codes
J05AR19 — Emtricitabine, tenofovir alafenamide and rilpivirineJ05AG05 — RilpivirineJ05AR08 — Emtricitabine, tenofovir disoproxil and rilpivirine
AHFS Codes
  • 08:18.08.16 — Nonnucleoside Reverse Transcriptase Inhibitors
PDB Entries
2zd1 / 2ze2 / 3bgr / 3mee / 3meg / 3qlh / 4g1q / 4icl / 4id5 / 4idk
show 7 more
FDA label
Download (558 KB)
MSDS
Download (568 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableAcquired Immune Deficiency Syndrome (AIDS) / Hepatic Impairment / Human Immunodeficiency Virus (HIV)1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV)1
1CompletedNot AvailableInfections, Human Immunodeficiency Virus and Hepatitis1
1CompletedDiagnosticHuman Volunteers1
1CompletedOtherHIV-DDI1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) / Oral Contraceptives (OC)1
1CompletedTreatmentBioavailability / Human Immunodeficiency Virus Type 1 (HIV-1) / Pharmacokinetics1
1CompletedTreatmentHealthy Participants1
1CompletedTreatmentHealthy Volunteers4
1CompletedTreatmentHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV)1
1CompletedTreatmentHepatitis C Virus (HCV)1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV)2
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
1CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
1RecruitingTreatmentInsulin Resistance1
1TerminatedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
1, 2Not Yet RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1, 2TerminatedPreventionHuman Immunodeficiency Virus (HIV) Infections1
1, 2WithdrawnTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedPreventionHuman Immunodeficiency Virus (HIV)1
2CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
2CompletedTreatmentInfection, Human Immunodeficiency Virus I1
2Not Yet RecruitingTreatmentContraception / Human Immunodeficiency Virus (HIV)1
2RecruitingTreatmentContraception / HIV-1-infection1
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2RecruitingTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
2, 3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
2, 3Enrolling by InvitationTreatmentHuman Immunodeficiency Virus (HIV)1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections3
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus-type 1 Infection1
3Active Not RecruitingTreatmentInfection, Human Immunodeficiency Virus I3
3CompletedTreatmentHCV Infections / Infection, Human Immunodeficiency Virus I1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Type 1 (HIV-1)2
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections / Pregnancy1
3CompletedTreatmentInfection, Human Immunodeficiency Virus I3
3Not Yet RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections2
4Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
4CompletedTreatmentCardiovascular Disease (CVD)1
4CompletedTreatmentHIV Associated Neurocognitive Disorders (HAND) / Neurocognitive Decline1
4CompletedTreatmentHealthy Volunteers2
4CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
4CompletedTreatmentInfection, Human Immunodeficiency Virus I1
4Not Yet RecruitingTreatmentHiv-positive1
4RecruitingTreatmentAntiretroviral Therapy Intolerance / Patients Compliance1
4RecruitingTreatmentHIV-1-infection / Neurocognitive Dysfunction1
4TerminatedTreatmentHuman Immunodeficiency Virus (HIV)1
4WithdrawnNot AvailableHuman Immunodeficiency Virus Type 1 (HIV-1) Infection1
Not AvailableActive Not RecruitingTreatmentAnti-Retroviral Agents / Dyslipidemias / Efavirenz / HIV-1-infection / Rilpivirine / Sustained Virologic Response1
Not AvailableCompletedTreatmentEfficacy of Rilpivirine-based Regimens as Switch Therapy1
Not AvailableRecruitingNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableRecruitingNot AvailableMinor Patient Treated by One or More Antiretroviral and for Which a Blood Test Has Been Performed1
Not AvailableRecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral
TabletOral25 mg
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral25 mg
Tablet, film coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5914331Yes1998-01-022018-01-02Us
US6043230Yes1998-01-252018-01-25Us
US9242986No2009-10-082029-10-08Us
US5814639Yes1997-03-292017-03-29Us
US6642245Yes2001-05-042021-05-04Us
US6703396Yes2001-09-092021-09-09Us
US5922695Yes1998-01-252018-01-25Us
US5935946Yes1998-01-252018-01-25Us
US5977089Yes1998-01-252018-01-25Us
US8592397No2004-01-132024-01-13Us
US8716264No2004-01-132024-01-13Us
US7125879No2002-08-092022-08-09Us
US6838464No2001-02-262021-02-26Us
US8080551No2003-04-112023-04-11Us
US8101629No2002-08-092022-08-09Us
US7067522No1999-12-202019-12-20Us
US7638522No2003-04-142023-04-14Us
US8129385No2007-10-052027-10-05Us
US8841310No2005-12-092025-12-09Us
US9296769No2012-08-152032-08-15Us
US7803788No2002-02-022022-02-02Us
US8754065No2012-08-152032-08-15Us
US7390791No2002-05-072022-05-07Us
US9457036No2004-01-132024-01-13Us
US9744181No2004-01-132024-01-13Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)241-243°CSun, et al.: J. Med. Chem., 41, 4648 (1998) Kashiwada, et al.: Bioorg. Med. Chem. Lett., 11, 183 (2001)
water solubility<0.1mg/mlUsach, et al. J Int AIDS Soc. 16(1): 18567. (2013)
logP4.86Usach, et al. J Int AIDS Soc. 16(1): 18567. (2013)
pKa5.6Usach, et al. J Int AIDS Soc. 16(1): 18567. (2013)
Predicted Properties
PropertyValueSource
Water Solubility0.0116 mg/mLALOGPS
logP3.8ALOGPS
logP5.47ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)12.93ChemAxon
pKa (Strongest Basic)5.16ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area97.42 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity111.74 m3·mol-1ChemAxon
Polarizability40.65 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9929
Blood Brain Barrier+0.8571
Caco-2 permeable+0.6609
P-glycoprotein substrateNon-substrate0.6933
P-glycoprotein inhibitor INon-inhibitor0.6604
P-glycoprotein inhibitor IINon-inhibitor0.7001
Renal organic cation transporterNon-inhibitor0.8261
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.8322
CYP450 3A4 substrateNon-substrate0.6778
CYP450 1A2 substrateInhibitor0.8256
CYP450 2C9 inhibitorNon-inhibitor0.9105
CYP450 2D6 inhibitorNon-inhibitor0.9202
CYP450 2C19 inhibitorNon-inhibitor0.806
CYP450 3A4 inhibitorNon-inhibitor0.9013
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5439
Ames testNon AMES toxic0.6229
CarcinogenicityNon-carcinogens0.9097
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.8139 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9027
hERG inhibition (predictor II)Non-inhibitor0.841
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzonitriles. These are organic compounds containing a benzene bearing a nitrile substituent.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzonitriles
Direct Parent
Benzonitriles
Alternative Parents
m-Xylenes / Styrenes / Aniline and substituted anilines / Aminopyrimidines and derivatives / Imidolactams / Hydropyrimidines / Heteroaromatic compounds / Secondary amines / Nitriles / Azacyclic compounds
show 2 more
Substituents
Benzonitrile / M-xylene / Xylene / Styrene / Aniline or substituted anilines / Aminopyrimidine / Hydropyrimidine / Pyrimidine / Imidolactam / Heteroaromatic compound
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aminopyrimidine, nitrile (CHEBI:68606)

Targets

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Rna-dna hybrid ribonuclease activity
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q72547
Uniprot Name
Reverse transcriptase/RNaseH
Molecular Weight
65223.615 Da
References
  1. Garvey L, Winston A: Rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor. Expert Opin Investig Drugs. 2009 Jul;18(7):1035-41. doi: 10.1517/13543780903055056. [PubMed:19548857]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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. Sharma D, Lau AJ, Sherman MA, Chang TK: Agonism of human pregnane X receptor by rilpivirine and etravirine: comparison with first generation non-nucleoside reverse transcriptase inhibitors. Biochem Pharmacol. 2013 Jun 1;85(11):1700-11. doi: 10.1016/j.bcp.2013.04.002. Epub 2013 Apr 9. [PubMed:23583259]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
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. Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [PubMed:23428312]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [PubMed:23428312]
  2. Aouri M, Barcelo C, Guidi M, Rotger M, Cavassini M, Hizrel C, Buclin T, Decosterd LA, Csajka C: Population Pharmacokinetics and Pharmacogenetics Analysis of Rilpivirine in HIV-1-Infected Individuals. Antimicrob Agents Chemother. 2016 Dec 27;61(1). pii: AAC.00899-16. doi: 10.1128/AAC.00899-16. Print 2017 Jan. [PubMed:27799217]
  3. Actual and Predicted Pharmacokinetic Interactions Between Anticonvulsants and Antiretrovirals [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [PubMed:23428312]
Kind
Protein
Organism
Human
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. Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [PubMed:23428312]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
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. Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [PubMed:23428312]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Other/unknown
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

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [PubMed:23428312]
Kind
Protein
Organism
Human
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. Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [PubMed:23428312]
Kind
Protein
Organism
Human
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. Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [PubMed:23428312]
Kind
Protein
Organism
Human
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. Weiss J, Haefeli WE: Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7. doi: 10.1016/j.ijantimicag.2013.01.004. Epub 2013 Feb 18. [PubMed:23428312]

Drug created on March 14, 2013 15:23 / Updated on September 21, 2018 00:15