Pharmacokinetics of the opioid antagonist N-methylnaltrexone and evaluation of its effects on gastrointestinal tract function in horses treated or not treated with morphine.

Objective: To determine the pharmacokinetics and effects of the morphine antagonist N-methylnaltrexone (MNTX) on gastrointestinal tract function in horses when administered alone and in combination with morphine.

Animals: 5 healthy adult horses.

Procedures: Horses were treated with MNTX (1 mg/kg, IV), and serial blood samples were collected for determination of drug pharmacokinetics. For evaluation of effects on the gastrointestinal tract when administered alone, MNTX was administered at a dosage of 0.75 mg/kg, IV, twice daily for 4 days. For evaluation of effects when administered concurrently with morphine, MNTX (0.75 mg/kg, IV, q 12 hours) and morphine (0.5 mg/kg, IV, q 12 hours) were administered for 6 days. Gastrointestinal variables evaluated were defecation frequency, weight of feces produced, fecal moisture content, intestinal transit time, and borborygmus scores.

Results: The time-concentration data for MNTX disposition best fit a 2-compartment model with a steady-state volume of distribution of 244.6 +/- 21.8 mL/kg, t1/2 of 47.04 +/- 11.65 minutes, and clearance of 11.43 +/- 1.06 mL/min/kg. Adverse effects were not observed at doses
Conclusions And Clinical Relevance: Because MNTX does not cross the blood-brain barrier, administration of the drug should not alter the analgesic effects of opioids and may attenuate the adverse gastrointestinal effects associated with use of opioids in horses.