Alvimopan

Các tên gọi khác (3) :

ADL 8-2698
Alvimopan
Entereg

Thuốc Gốc

Small Molecule

CAS: 170098-38-1

ATC: A06AH02

ĐG : Adolor Corp. , http://www.adolor.com

CTHH: C₂₅H₃₂N₂O₄

PTK: 424.5326

Alvimopan is a peripherally acting μ opioid antagonist. It is used to avoid postoperative ileus following small or large bowel resection and accelerates the gastrointestinal recovery period.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₂₅H₃₂N₂O₄

Phân tử khối

424.5326

Monoisotopic mass

424.236207522

InChI

InChI=1S/C25H32N2O4/c1-18-16-27(12-11-25(18,2)21-9-6-10-22(28)14-21)17-20(24(31)26-15-23(29)30)13-19-7-4-3-5-8-19/h3-10,14,18,20,28H,11-13,15-17H2,1-2H3,(H,26,31)(H,29,30)/t18-,20-,25+/m0/s1

InChI Key

InChIKey=UPNUIXSCZBYVBB-JVFUWBCBSA-N

IUPAC Name

2-[(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanamido]acetic acid

Traditional IUPAC Name

alvimopan

SMILES

C[C@H]1CN(C[C@H](CC2=CC=CC=C2)C(=O)NCC(O)=O)CC[C@@]1(C)C1=CC(O)=CC=C1

Độ hòa tan

<0.1 mg/mL

logP

0.82

logS

-4.7

pKa (strongest acidic)

3.71

pKa (Strongest Basic)

10.66

PSA

89.87 Å²

Refractivity

120.56 m³·mol^-1

Polarizability

46.77 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Rule of Five

true

Ghose Filter

true

MDDR-Like Rule

true

Cơ Chế Tác Dụng : Alvimopan is a peripherally acting μ opioid antagonist. It is used to avoid postoperative ileus following small or large bowel resection and accelerates the gastrointestinal recovery period. Alvimopan competitively binds to mu-opioid receptor in the gastrointestinal tract. Unlike methylnaltrexone (another peripherally acting mu-receptor antagonist) that bears a quaternary amine, alvimopan owes its selectivity for peripheral receptors to its kinetics. Alvimopan binds to peripheral mu-receptors with a Ki of 0.2 ng/mL and dissociates slower than most other ligands.

Dược Động Học :

▧ Absorption :
Alvimopan's high affinity for the peripheral mu-receptor results in an absolute oral bioavailability of less than 7%.
▧ Volume of Distribution :
* 30±10 L
▧ Protein binding :
80% to 90% of systemically available alvimopan is bound to plasma protein.
▧ Metabolism :
Alvimopan undergoes no significant hepatic metabolism, but is metabolized by intestinal flora. Gut metabolism produces an active metabolite with no clinically significant contribution to drug effect.
▧ Route of Elimination :
Biliary secretion was considered the primary pathway for alvimopan elimination. Unabsorbed drug and unchanged alvimopan resulting from biliary excretion were then hydrolyzed to its ‘metabolite’ by gut microflora. Feces (via biliary excretion) & urine (35%)
▧ Half Life :
10 to 17 hours (gut metabolite: 10 to 18 hours)
▧ Clearance :
* 402 ± 89 mL/min

Chỉ Định : Used to accelerate the time to upper and lower gastrointestinal recovery following partial large or small bowel resection surgery with primary anastomosis. Also investigated for use in the treatment of pain (acute or chronic).

Tương Tác Thuốc :

Alfentanil Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Amiodarone Decreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
Atorvastatin Decreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
Buprenorphine Opioids like buprenorphine may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Consider therapy modification.
Butorphanol Opioid analgesics such as butorphanol may enhance the adverse/toxic effect of alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. According to alvimopan prescribing information, alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Monitor for increased alvimopan adverse effects in patients using opioids prior to alvimopan.
Clarithromycin Decreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
Clotrimazole Decreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
Codeine Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Dextromoramide Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Dextropropoxyphene Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Dezocine Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Difenoxin Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Dihydrocodeine Opioids may enhance Alvimopan toxicity, especially when opiate use for more than 7 days is in place prior to alvimopan initiation. Alvimopan is contraindicated for use if patients have been dosed with opioids for more than 7 consecutive days.
Diphenoxylate Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Dipipanone Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Fentanyl Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Heroin Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Hydrocodone Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Hydromorphone Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Ivacaftor Decreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
Levomethadyl Acetate Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Levorphanol Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Methadone Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Morphine Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Nalbuphine Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Oxycodone Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Oxymorphone Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Papaverine Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Pentazocine Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Pethidine Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Quinidine Decreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
Sufentanil Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Tapentadol Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Tramadol Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.

Liều Lượng & Cách Dùng : Capsule, coated - Oral - 12mg

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Entereg 12 mg capsule

Giá bán buôn : USD >79.5

Đơn vị tính : capsule

Nhà Sản Xuất

Công ty : Cubist Pharmaceuticals

Sản phẩm biệt dược : Entereg

Đóng gói

Công ty : Adolor Corp.

Website : http://www.adolor.com
Công ty : GlaxoSmithKline Inc.

Website : http://www.gsk.com
Công ty : Pharmaceutics International Inc.

Website : http://www.pharm-int.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB06274

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5488548

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=99443242

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D02878

ChemSpider

http://www.chemspider.com/Chemical-Structure.4589864.html

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/11227-010-30

PharmGKB

http://www.pharmgkb.org/drug/PA164754864

Wikipedia

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

RxList

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

Drugs.com

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

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