Use of methylnaltrexone and related compounds

#The present invention is directed at the treatment of certain side effects associated with the use of opioids as analgesics. In particular the present invention is directed at treating opioid-induced inhibition of gastrointestinal motility and constipation.

#Opioids are effective analgesics. However, their use is associated with a number of undesirable side effects. One such effect is constipation. Opioid-induced changes in gastrointestinal motility are almost universal when these drugs are used to treat pain, and at times may limit their use, leaving the patient in pain. Common treatments of bulking agents and laxatives have limited efficacy and may be associated with side effects such as electrolyte imbalances.

#One treatment for opioid side effects is the use of opioid antagonists which cross the blood-brain-barrier, or which are administered directly into the central nervous system. Opioid antagonists such as naltrexone and naloxone have been administered intramuscularly or orally to treat opioid induced side effects. Naltrexone and naloxone are highly lipid soluble and rapidly diffuse across biological membranes, including the blood-brain barrier. However, naltrexone, naloxone, nalmefene, and other opioid antagonists which may reverse many opioid side effects have a narrow therapeutic window before they are observed to reverse the desired analgesic effect of the opioid being used.

#FIG. 1A is a graph representing plasma concentrations of MNTX following administration of 6.4 mg/kg of uncoated MNTX.

#FIG. 1B is a graph representing plasma concentrations of MNTX following administration of 6.4 mg/kg of enterically coated MNTX.

#FIG. 1C is a graph representing plasma concentrations of MNTX following administration of 3.2 mg/kg of enterically coated MNTX.

#The present invention is directed at methods for preventing and treating opioid-induced inhibition of gut motility and constipation.

#The method for preventing opioid-induced decreased gut motility and constipation comprises administering enterically coated methylnaltrexone or other quaternary derivatives of noroxymorphone as disclosed in U.S. Pat. No. 4,176,186 to Goldberg et al. (herein incorporated by reference) to a patient prior to or simultaneously with the administration of an opioid.

#The method for treating opioid-induced inhibition of gut motility and constipation comprises administering enterically coated methylnaltrexone or other quaternary derivatives of noroxymorphone to a patient after the onset of the side effect.