Abstract
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 IVINTX (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 dis- position best fit a 2-compartment model with a steady-state volume of distribution of 244.6 ± 21.8 mL/kg, t1/2 of 4704 ± 11.65 minutes, and clearance of 11.43 ± 1.06 mL/min/kg. Adverse effects were not observed at doses ≤ 1 mg/kg. Administration of MNTX increased daily fecal weight. When administered concurrently with morphine, MNTX partially prevented the effects of morphine on the gastrointestinal tract by increasing defecation frequency, fecal weight, fecal moisture content, and borborygmus score, and by preventing increases in intestinal transit time. Conclusions and clinical relevance - Because MNTX does not cross the blood-brain barrier, adminstration 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 998-1004 |
| Number of pages | 7 |
| Journal | American Journal of Veterinary Research |
| Volume | 67 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2006 |
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Pharmacokinetics of the opioid antagonist N-methylnaltrexone and evaluation of its effects on gastrointestinal tract function in horses treated or not treated with morphine. / Boscan, Pedro; Van Hoogmoed, Linda M.; Pypendop, Bruno H; Farver, Thomas B; Snyder, Jack R.
In: American Journal of Veterinary Research, Vol. 67, No. 6, 06.2006, p. 998-1004.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacokinetics of the opioid antagonist N-methylnaltrexone and evaluation of its effects on gastrointestinal tract function in horses treated or not treated with morphine
AU - Boscan, Pedro
AU - Van Hoogmoed, Linda M.
AU - Pypendop, Bruno H
AU - Farver, Thomas B
AU - Snyder, Jack R.
PY - 2006/6
Y1 - 2006/6
N2 - 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 IVINTX (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 dis- position best fit a 2-compartment model with a steady-state volume of distribution of 244.6 ± 21.8 mL/kg, t1/2 of 4704 ± 11.65 minutes, and clearance of 11.43 ± 1.06 mL/min/kg. Adverse effects were not observed at doses ≤ 1 mg/kg. Administration of MNTX increased daily fecal weight. When administered concurrently with morphine, MNTX partially prevented the effects of morphine on the gastrointestinal tract by increasing defecation frequency, fecal weight, fecal moisture content, and borborygmus score, and by preventing increases in intestinal transit time. Conclusions and clinical relevance - Because MNTX does not cross the blood-brain barrier, adminstration 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.
AB - 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 IVINTX (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 dis- position best fit a 2-compartment model with a steady-state volume of distribution of 244.6 ± 21.8 mL/kg, t1/2 of 4704 ± 11.65 minutes, and clearance of 11.43 ± 1.06 mL/min/kg. Adverse effects were not observed at doses ≤ 1 mg/kg. Administration of MNTX increased daily fecal weight. When administered concurrently with morphine, MNTX partially prevented the effects of morphine on the gastrointestinal tract by increasing defecation frequency, fecal weight, fecal moisture content, and borborygmus score, and by preventing increases in intestinal transit time. Conclusions and clinical relevance - Because MNTX does not cross the blood-brain barrier, adminstration 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33745642426&partnerID=8YFLogxK
U2 - 10.2460/ajvr.67.6.998
DO - 10.2460/ajvr.67.6.998
M3 - Article
C2 - 16740093
AN - SCOPUS:33745642426
VL - 67
SP - 998
EP - 1004
JO - American Journal of Veterinary Research
JF - American Journal of Veterinary Research
SN - 0002-9645
IS - 6
ER -