Boceprevir

Các tên gọi khác (2) :

SCH 503034
Victrelis

Thuốc Gốc

Small Molecule

CAS: 394730-60-0

ATC: J05AE12

CTHH: C₂₇H₄₅N₅O₅

PTK: 519.6767

Boceprevir is a direct acting protease inhibitor for the treatment of hepatitis C. It also has two isomers in which the S isomer is more active than the R-isomer. FDA approved on May 13, 2011.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₂₇H₄₅N₅O₅

Phân tử khối

519.6767

Monoisotopic mass

519.342069575

InChI

InChI=1S/C27H45N5O5/c1-25(2,3)20(30-24(37)31-26(4,5)6)23(36)32-13-15-17(27(15,7)8)18(32)22(35)29-16(19(33)21(28)34)12-14-10-9-11-14/h14-18,20H,9-13H2,1-8H3,(H2,28,34)(H,29,35)(H2,30,31,37)/t15-,16?,17-,18-,20+/m0/s1

InChI Key

InChIKey=LHHCSNFAOIFYRV-DOVBMPENSA-N

IUPAC Name

3-{[(1R,2S,5S)-3-[(2S)-2-[(tert-butylcarbamoyl)amino]-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2-yl]formamido}-4-cyclobutyl-2-oxobutanamide

Traditional IUPAC Name

boceprevir

SMILES

[H][C@]12CN([C@H](C(=O)NC(CC3CCC3)C(=O)C(N)=O)[C@@]1([H])C2(C)C)C(=O)[C@@H](NC(=O)NC(C)(C)C)C(C)(C)C

Độ hòa tan

2.34e-02 g/l

logP

1.78

logS

-4.3

pKa (strongest acidic)

12.44

pKa (Strongest Basic)

-0.91

PSA

150.7 Å²

Refractivity

138.2 m³·mol^-1

Polarizability

56.55 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

MDDR-Like Rule

true

Dược Lực Học : Telaprevir is a direct-acting antiviral agent (DAA) against the hepatitis C virus.

Cơ Chế Tác Dụng : Boceprevir is a direct acting protease inhibitor for the treatment of hepatitis C. It also has two isomers in which the S isomer is more active than the R-isomer. FDA approved on May 13, 2011. Boceprevir inhibits replication of the hepatitis C virus by binding reversibly to nonstructural protein 3/4a (NS3 and NS4A respectively) serine protease. NS4A is a cofactor that works with NS3 for viral replication.

Dược Động Học :

▧ Absorption :
Food increases exposure of boceprevir by up to 65% relative to fasting state. However, type of food and time of meal does not affect bioavailability of boceprevir and thus can be taken without regards to food. Tmax = 2 hours; Time to steady state, three times a day dosing = 1 day; Cmax, 400 mg single dose, healthy subject = 557 ng/mL; AUC ∞, healthy subject = 2020 ng · h/mL;
▧ Volume of Distribution :
~722 L
▧ Protein binding :
~75%
▧ Metabolism :
Hepatically metabolized by the aldo-ketoreductase pathway into inactive metabolites via reduction. To a lesser extent, CYP3A4 and CYP3A5 is also involved in the metabolism of boceprevir (oxidative process).
▧ Route of Elimination :
Removed via feces (79%) and urine (9%) which suggest some degree of hepatic excretion.
▧ Half Life :
Mean plasma half-life = 3.4 hours
▧ Clearance :
Mean total body clearance (Cl/F) = 161 L/h

Chỉ Định : Treatment of chronic hepatitis C genotype 1 in patients that have a compensated liver (as a result of liver diseases like cirrhosis) and are previously untreated or therapy with peginterferon alfa and ribavirin has failed.

Tương Tác Thuốc :

Alfuzosin Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Atorvastatin Boceprevir increases the exposure of atorvastatin. Concomitant therapy should be closely monitored.
Carbamazepine Strong CYP3A4 inducers will decrease levels of boceprevir. Concomitant therapy is contraindicated.
Cisapride Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Conivaptan Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Dihydroergotamine Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Drospirenone Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Etravirine The exposure of etravirine decreases whereas boceprevir's exposure increased. Therapeutic implications of this observation is unknown.
Fosphenytoin Strong CYP3A4 inducers will decrease levels of boceprevir. Concomitant therapy is contraindicated.
Lomitapide Boceprevir increases levels of lomipatide by 27 folds by inhibiting CYP3A4 metabolism. Concomitant therapy of Boceprevir and strong CYP3A4 inhibitors (such as clarithromycin, conivaptan, indinavir, intraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, variconazole) with lomipatide is contraindicated.
Midazolam Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Phenobarbital Strong CYP3A4 inducers will decrease levels of boceprevir. Concomitant therapy is contraindicated.
Phenytoin Strong CYP3A4 inducers will decrease levels of boceprevir. Concomitant therapy is contraindicated.
Pimozide Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Ponatinib Strong CYP3A4 inhibitors may increase levels of ponatinib. Monitor concomitant therapy closely.
Pravastatin Boceprevir increases pravastatin AUC by 60% with boceprevir. Concomitant therapy should be closely monitored.
Rifampicin Strong CYP3A4 inducers will decrease levels of boceprevir. Concomitant therapy is contraindicated.
Sirolimus Boceprevir increases levels of sirolimus by affecting CYP3A4 metabolism. Concomitant therapy requires close monitoring.
St. John's Wort Strong CYP3A4 inducers will decrease levels of boceprevir. Concomitant therapy is contraindicated.
Tacrolimus Boceprevir increases levels of tacrolimus by affecting CYP3A4 metabolism. Concomitant therapy requires close monitoring.
Tadalafil Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.

Liều Lượng & Cách Dùng : Capsule - Oral - 200 mg

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty : Merck & Co., Inc.

Sản phẩm biệt dược : Victrelis

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB08873

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D08876

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0085-0314-02

Wikipedia

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

RxList

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

Drugs.com

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

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