Alvimopan

Alvimopan (trade name Entereg) is a drug which behaves as a peripherally acting μ-opioid antagonist. With the limited ability to cross the blood–brain barrier and reach the μ-opioid receptors of the central nervous system, the clinically undesirable effects of centrally acting opioid antagonists (like reversal of opioid-mediated analgesia) are avoided without affecting the intended blockade of μ-opioid receptors in the gastrointestinal tract. It is currently only Food and Drug Administration approved for the treatment of postoperative ileus which it received in May 2008. Alvimopan (trade name Entereg) is a drug which behaves as a peripherally acting μ-opioid antagonist. With the limited ability to cross the blood–brain barrier and reach the μ-opioid receptors of the central nervous system, the clinically undesirable effects of centrally acting opioid antagonists (like reversal of opioid-mediated analgesia) are avoided without affecting the intended blockade of μ-opioid receptors in the gastrointestinal tract. It is currently only Food and Drug Administration approved for the treatment of postoperative ileus which it received in May 2008. Alvimopan is indicated in people to avoid postoperative ileus following partial large or small bowel resection with primary anastomosis. Alvimopan accelerates the gastrointestinal recovery period as defined by time to first bowel movement or flatus. The most common side effects associated with alvimopan are: Alvimopan is absolutely contraindicated in patients who have taken therapeutic doses of opioids for more than seven consecutive days immediately prior to when alvimopan would be initiated because individuals with recent exposure to opioids are expected to be more sensitive to the effects of μ-opioid receptor antagonists. The peripheral site of action of alvimopan suggests that such a heightened sensitivity would precipitate gastrointestinal effects beyond dyspepsia. Alvimopan is not a substrate for the cytochrome P450 enzyme system. Therefore, no interactions are expected with hepatically metabolized drugs. Alvimopan is substrate for P-glycoprotein. Thus, interactions are to be expected with known P-glycoprotein inhibitors such as amiodarone, bepridil, diltiazem, ciclosporin, itraconazole, quinine, quinidine, spironolactone, and verapamil. Alvimopan competitively binds to μ-opioid receptor in the gastrointestinal tract. Unlike methylnaltrexone (another peripherally acting μ-receptor antagonist) that bears a quaternary amine, alvimopan owes its selectivity for peripheral receptors to its kinetics. Alvimopan binds to peripheral μ-receptors with a Ki of 0.2 ng/mL and dissociates more slowly than most other ligands. Peak plasma concentration (Cmax) of alvimopan is reached approximately 2 hours after oral dosing, while the Cmax for metabolite occurs 36 hours after an oral dose. Alvimopan's high affinity for the peripheral μ-receptor results in an absolute bioavailability less than 7%. 80% to 90% of systemically available alvimopan is bound to plasma protein. At steady state, the volume of distribution is approximately 30 liters. 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.