methylnaltrexone and Urinary-Retention

Progenics Pharmaceuticals Inc and Wyeth Pharmaceuticals are developing methylnaltrexone, a micro-receptor opioid antagonist derived from naltrexone by the addition of a methyl group. The intravenous formulation of methylnaltrexone is currently in phase III clinical trials for the potential treatment of postoperative ileus.

Topics: Analgesics, Opioid; Gastrointestinal Motility; Humans; Ileus; Naltrexone; Postoperative Complications; Postoperative Nausea and Vomiting; Quaternary Ammonium Compounds; Receptors, Opioid, mu; Urinary Retention

Peripheral mechanisms may be involved in opioid actions on the urinary bladder. This double-blind study investigated whether opioid inhibition of bladder function is reversed by methylnaltrexone, a peripheral opioid antagonist. Thirteen healthy male volunteers received an intravenous (i.v.) infusion of remifentanil, 0.15 mcg/kg/min, then a single i.v. dose of study medication (methylnaltrexone 0.3 mg/kg, naloxone 0.01 mg/kg, or saline). Urodynamics were measured with indwelling bladder and rectal catheters, and pupil size was assessed with infrared pupillometry. Remifentanil decreased detrusor pressure in 21/25 sessions and caused complete urinary retention in 18/25. Voiding was possible in 7/7, 5/12, and 0/6 sessions after naloxone, methylnaltrexone, and saline, respectively (P=0.0013). Remifentanil caused marked miosis that was reversed by naloxone, but not methylnaltrexone or placebo (P<0.0001). The pupil data confirm that methylnaltrexone did not reverse central opioid effects. Reversal of urinary retention by methylnaltrexone indicates that peripheral mechanisms may play a role in opioid-induced bladder dysfunction.

Topics: Adult; Analgesics, Opioid; Cross-Over Studies; Double-Blind Method; Humans; Infusions, Intravenous; Male; Middle Aged; Miosis; Muscle Contraction; Naloxone; Naltrexone; Narcotic Antagonists; Piperidines; Quaternary Ammonium Compounds; Remifentanil; Treatment Outcome; Urinary Bladder; Urinary Retention; Urination

Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, has been studied in adults for the treatment of opioid-induced constipation in advanced illness. Here, the authors document the first neonate to receive methylnaltrexone in an attempt to resolve morphine-induced urinary retention. An asphyxiated term newborn infant underwent induced hypothermia and received morphine by continuous intravenous infusion. After 36 h, the patient developed progressive urinary retention (calculated bladder volume 63 ml), followed by venous congestion of the lower extremities. Attempted bladder catheterisation was unsuccessful. Voiding occurred within 20 min after intravenous administration of methylnaltrexone (0.15 mg/kg body weight). A relapse of urinary retention 24 h later responded well to a second dose of methylnaltrexone. There were no adverse effects and no opioid withdrawal symptoms. The neonate had normal findings in cranial MRI that was performed after elective cessation of induced hypothermia.

Topics: Analgesics, Opioid; Humans; Infant, Newborn; Male; Morphine; Naltrexone; Narcotic Antagonists; Quaternary Ammonium Compounds; Ultrasonography; Urinary Retention