Rilpivirine

Các tên gọi khác (3) :

4-{[4-({4-[(e)-2-cyanovinyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile
TMC 278
TMC278

Thuốc Gốc

Small Molecule

CAS: 500287-72-9

ATC: J05AG05

CTHH: C₂₂H₁₈N₆

PTK: 366.4185

Rilpivirine is non-nucleoside reverse transcriptase inhibitor (NNRTI) which is used for the treatment of HIV-1 infections in treatment-naive patients. It is a diarylpyrimidine, a class of molecules that resemble pyrimidine nucleotides found in DNA. Because of its flexible chemical structure, resistance of rilpivirine is less likely to develop than other NNRTI's. FDA approved on May 20, 2011.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₂₂H₁₈N₆

Phân tử khối

366.4185

Monoisotopic mass

366.159294606

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+

InChI Key

InChIKey=YIBOMRUWOWDFLG-ONEGZZNKSA-N

IUPAC Name

4-{[4-({4-[(1E)-2-cyanoeth-1-en-1-yl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile

Traditional IUPAC Name

rilpivirine

SMILES

CC1=CC(\C=C\C#N)=CC(C)=C1NC1=CC=NC(NC2=CC=C(C=C2)C#N)=N1

Độ tan chảy

241-243°C

Độ hòa tan

1.16e-02 g/l

logP

5.47

logS

-4.5

pKa (strongest acidic)

12.93

pKa (Strongest Basic)

5.16

PSA

97.42 Å²

Refractivity

111.74 m³·mol^-1

Polarizability

40.78 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Ghose Filter

true

Dược Lực Học : Rilpivirine is the most potent NNRTI and has a EC50 of 0.73 nM in vitro against HIV-1 because its chemical structure allowed for better binding to reverse transcriptase.

Cơ Chế Tác Dụng : Rilpivirine is non-nucleoside reverse transcriptase inhibitor (NNRTI) which is used for the treatment of HIV-1 infections in treatment-naive patients. It is a diarylpyrimidine, a class of molecules that resemble pyrimidine nucleotides found in DNA. Because of its flexible chemical structure, resistance of rilpivirine is less likely to develop than other NNRTI's. FDA approved on May 20, 2011. Rilpivirine is an NNRTI which binds to reverse transcriptase which results in a block in RNA and DNA- dependent DNA polymerase activities. One such activity is HIV-1 replication. Intracellular phosphorylation is not necessary for its antiviral activity. Because of the structure of rilpivirine is flexible around the aromatic rings, the molecule can have multiple conformations so that can bind to residues in the reverse transcriptase enzyme which have a lower mutation rate.

Dược Động Học :

▧ Absorption :
Rilpivirine demonstrates dose-dependent pharmacokinetics and does not change between subscutaneous, IV, and intramuscular administration. Absorption increases with meals. Tmax, oral administration = 4 hours;
▧ Protein binding :
>99% protein bound.
▧ Metabolism :
Mainly hepatically metabolized by CYP3A4. 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.
▧ Route of Elimination :
Excreted fecally (85%, 25% as unchanged drug) and urine (6%, <1% as unchanged drug)
▧ Half Life :
34-55 hours after oral administration

Độc Tính : Oral, mouse: LD50 = 300 mg/kg; Oral, rabbit: LD50 = 3200 mg/kg; Oral, rat: LD50 = 980 mg/kg.

Chỉ Định : Treatment of HIV-1 infections in treatment-naive patients with HIV-1 RNA ≤100,000 copies/mL in combination with at least 2 other antiretroviral agents.

Tương Tác Thuốc :

Carbamazepine Strong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
Delavirdine Concentration of rilpivirine increases by affecting CYP3A4 metabolism. Concomitant use is contraindicated. Rilpivirine should not be used with other NNRTI's.
Dexamethasone Strong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
Efavirenz Concentration of rilpivirine decreases by affecting CYP3A4 metabolism. Concomitant use is contraindicated. Rilpivirine should not be used with other NNRTI's.
Esomeprazole Proton-pump inhibitors increase gastric pH which causes a decrease in the exposure of rilpivirine thus reducing efficacy.
Etravirine Rilpivirine, when used concomitantly with etravirine, may experience a decrease in serum concentration. It is recommended to avoid concurrent therapy. Use of rilpivirine and other NNRTIs is containdicated.
Famotidine Histamine-2 receptor antagonists increase gastric pH which causes a decrease in the exposure of rilpivirine thus reducing efficacy.
Lansoprazole Proton-pump inhibitors increase gastric pH which causes a decrease in the exposure of rilpivirine thus reducing efficacy.
Methadone Dose adjustment and clinical monitoring of rilpivirine may be necessary if coadministered with methadone.
Omeprazole Proton-pump inhibitors increase gastric pH which causes a decrease in the exposure of rilpivirine thus reducing efficacy.
Oxcarbazepine Strong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
Pantoprazole Proton-pump inhibitors increase gastric pH which causes a decrease in the exposure of rilpivirine thus reducing efficacy.
Phenobarbital Strong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
Phenytoin Strong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
Rabeprazole Proton-pump inhibitors increase gastric pH which causes a decrease in the exposure of rilpivirine thus reducing efficacy.
Ranitidine Histamine-2 receptor antagonists increase gastric pH which causes a decrease in the exposure of rilpivirine thus reducing efficacy.
Rifabutin Strong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
Rifampicin Strong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.
Rifapentine Strong inducers of CYP3A4 decrease the exposure of rilpivirine thus decreasing efficacy.

Liều Lượng & Cách Dùng : Tablet - Oral - 25 mg

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty : Janssen Therapeutics

Sản phẩm biệt dược : Edurant

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB08864

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D09720

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/59676-278-01

Wikipedia

http://en.wikipedia.org/wiki/Rilpivirine

RxList

http://www.rxlist.com/edurant-drug.htm

Drugs.com

http://www.drugs.com/cdi/rilpivirine.html

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