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药品详细

Alvimopan(爱维莫潘)

化学结构式图
中文名
爱维莫潘
英文名
Alvimopan
分子式
C25H32N2O4
化学名
2-[(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanamido]acetic acid
分子量
Average: 424.5326
Monoisotopic: 424.236207522
CAS号
170098-38-1
ATC分类
A06A 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

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.

生产厂家
  • Adolor corp
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Buchler MW, Seiler CM, Monson JR, Flamant Y, Thompson-Fawcett MW, Byrne MM, Mortensen ER, Altman JF, Williamson R: Clinical trial: alvimopan for the management of postoperative ileus after abdominal surgery: results of an international randomised, double-blind, multicentre, placebo-controlled clinical study. Aliment Pharmacol Ther. 2008 Mar 28. Pubmed
  2. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm194328.htm
  3. Wang S, Shah N, Philip J, Caraccio T, Feuerman M, Malone B: Role of alvimopan (entereg) in gastrointestinal recovery and hospital length of stay after bowel resection. P T. 2012 Sep;37(9):518-25. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Phenylpiperidines
  • Amino Acids
Substructures
  • Hydroxy Compounds
  • Acetates
  • Phenols and Derivatives
  • Amino Ketones
  • Benzene and Derivatives
  • Phenylpiperidines
  • Carboxylic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Amino Acids
  • Phenyl Esters
  • Piperidines
适应症
药理
Indication 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).
Pharmacodynamics Not Available
Mechanism of action 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.
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
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
water solubility <0.1 mg/mL FDA Label
Predicted Properties
Property Value Source
water solubility 8.34e-03 g/l ALOGPS
logP 3.25 ALOGPS
logP 0.82 ChemAxon
logS -4.7 ALOGPS
pKa (strongest acidic) 3.71 ChemAxon
pKa (strongest basic) 10.66 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 89.87 ChemAxon
rotatable bond count 8 ChemAxon
refractivity 120.56 ChemAxon
polarizability 46.77 ChemAxon
药物相互作用
Drug Interaction
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.
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.
Meperidine 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.
Propoxyphene 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.
食物相互作用
Not Available

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