Meperidine pharmacokinetics and effects on physiologic parameters and thermal threshold following intravenous administra
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(2020) 16:368
RESEARCH ARTICLE
Open Access
Meperidine pharmacokinetics and effects on physiologic parameters and thermal threshold following intravenous administration of three doses to horses Briana D. Hamamoto-Hardman1, Eugene P. Steffey2, Daniel S. McKemie1, Philip H. Kass3 and Heather K. Knych1,4*
Abstract Background: Meperidine is a synthetic opioid that belongs to the phenylpiperidine class and is a weak mu receptor agonist. In horses there are a limited number of published studies describing the analgesic effects of systemically administered meperidine in horses. The objective of this study was to describe the pharmacokinetics, behavioral and physiologic effects and effect on thermal threshold of three doses of intravenously administered meperidine to horses. Eight University owned horses (four mares and four geldings, aged 3–8 years were studied using a randomized balanced 4-way cross-over design. Horses received a single intravenous dose of saline, 0.25, 0.5 and 1.0 mg/kg meperidine. Blood was collected before administration and at various time points until 96 hours post administration. Plasma and urine samples were analyzed for meperidine and normeperidine by liquid chromatography-mass spectrometry and plasma pharmacokinetics determined. Behavioral and physiologic data (continuous heart rate, step counts, packed cell volume, total plasma protein and gastrointestinal sounds) were collected at baseline through 6 hours post administration. The effect of meperidine administration on thermal nociception was determined and thermal excursion calculated. Results: Meperidine was rapidly converted to the metabolite normeperidine. The volume of distribution at steady state and systemic clearance (mean ± SD) ranged from 0.829 ± 0.138–1.58 ± 0.280 L/kg and 18.0 ± 1.4–22.8 ± 3.60 mL/min/kg, respectively for 0.5–1.0 mg/kg doses. Adverse effects included increased dose-dependent central nervous excitation, heart rate and cutaneous reactions. Significant effects on thermal nociception were short lived (up to 45 minutes at 0.5 mg/kg and 15 minutes at 1.0 mg/kg). Conclusions: Results of the current study do not support routine clinical use of IV meperidine at a dose of 1 mg/kg to horses. Administration of 0.5 mg/kg may provide short-term analgesia, however, the associated inconsistent and/ or short-term adverse effects suggest that its use as a sole agent at this dose, at best, must be cautiously considered. Keywords: Horse, Meperidine, Opioid, Pharmacokinetics, Pharmacodynamics, Thermal threshold
* Correspondence: [email protected] 1 K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California-Davis, CA 95616 Davis, USA 4 Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, USA Full list of author information is available at the end of the article
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, d
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