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

Pedro Boscan, Linda M. Van Hoogmoed, Bruno H Pypendop, Thomas B Farver, Jack R. Snyder

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)998-1004
Number of pages7
JournalAmerican Journal of Veterinary Research
Volume67
Issue number6
DOIs
StatePublished - Jun 2006

Fingerprint

narcotic antagonists
Narcotic Antagonists
morphine
Morphine
pharmacokinetics
Horses
gastrointestinal system
Gastrointestinal Tract
Pharmacokinetics
horses
gastrointestinal transit
defecation
narcotics
Defecation
Weights and Measures
Opioid Analgesics
water content
drugs
blood-brain barrier
analgesic effect

ASJC Scopus subject areas

  • veterinary(all)

Cite this

@article{feb3e5051e6749f287ca0a91a559a762,
title = "Pharmacokinetics of the opioid antagonist N-methylnaltrexone and evaluation of its effects on gastrointestinal tract function in horses treated or not treated with morphine",
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.",
author = "Pedro Boscan and {Van Hoogmoed}, {Linda M.} and Pypendop, {Bruno H} and Farver, {Thomas B} and Snyder, {Jack R.}",
year = "2006",
month = "6",
doi = "10.2460/ajvr.67.6.998",
language = "English (US)",
volume = "67",
pages = "998--1004",
journal = "American Journal of Veterinary Research",
issn = "0002-9645",
publisher = "American Veterinary Medical Association",
number = "6",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=33745642426&partnerID=8YFLogxK

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 -