Meperidine pharmacokinetics and effects on physiologic parameters and thermal threshold following intravenous administration of three doses to horses.
Abstract: 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.
Publication Date: 2020-10-01 PubMed ID: 32998730PubMed Central: PMC7528573DOI: 10.1186/s12917-020-02564-4Google Scholar: Lookup
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Summary
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This study investigates the effects of three different doses of meperidine, a synthetic opioid, on horses when administered intravenously. It reveals that while the drug can provide short-term pain relief, it can also produce adverse side effects, casting doubts on its routine use as a standalone treatment in equine medicine.
Research design and outcomes
The detailed explanation of the study is as follows:
- The investigation involved eight horses owned by a university. The subjects were divided evenly between males (geldings) and females (mares) aged between 3-8 years. The study used a randomized balanced 4-way cross-over design.
- The horses were given a single intravenous dose of either saline, or one of three doses of meperidine: 0.25 mg/kg, 0.5 mg/kg, or 1.0 mg/kg. Blood samples were collected before administration and at several stages up to 96 hours afterward.
- Plasma and urine samples were then evaluated to determine the levels of meperidine and its metabolite normeperidine, using a technique known as liquid chromatography-mass spectrometry.
- Various physiological measurements were monitored over the course of 6 hours post administration, including heart rate, step counts, packed cell volume, total plasma protein, and gastrointestinal sounds. The team also studied the impact of meperidine on thermal nociception (the animal’s reaction to potential harmful heat sources), calculating the thermal excursion observed in the process.
- The research found that meperidine was quickly metabolized into normeperidine. For the 0.5-1.0 mg/kg doses, the volume of distribution at steady state ranged from 0.829 ± 0.138-1.58 ± 0.280 L/kg, and systemic clearance from 18.0 ± 1.4-22.8 ± 3.60 mL/min/kg.
- Notable side effects were dose-dependent central nervous excitation, an increased heart rate, and skin reactions. The effects on thermal nociception were seen to be short-lived; up to 45 minutes at the 0.5 mg/kg dose and only up to 15 minutes at the 1.0 mg/kg dose.
Conclusion
The final results of this study do not endorse the general clinical use of intravenous meperidine at a dose of 1 mg/kg in horses. It suggests that while a 0.5 mg/kg dose could provide temporary pain relief, the accompanying erratic and/or short-term adverse effects imply that cautious consideration must be taken if it is to be used as the only agent at this dosage.
Cite This Article
APA
Hamamoto-Hardman BD, Steffey EP, McKemie DS, Kass PH, Knych HK.
(2020).
Meperidine pharmacokinetics and effects on physiologic parameters and thermal threshold following intravenous administration of three doses to horses.
BMC Vet Res, 16(1), 368.
https://doi.org/10.1186/s12917-020-02564-4 Publication
Researcher Affiliations
- K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California-Davis, CA, 95616, Davis, USA.
- Department of Veterinary Surgery and Radiology, School of Veterinary Medicine, University of California, Davis, USA.
- K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California-Davis, CA, 95616, Davis, USA.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, USA.
- K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California-Davis, CA, 95616, Davis, USA. hkknych@ucdavis.edu.
- Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, USA. hkknych@ucdavis.edu.
MeSH Terms
- Administration, Intravenous / veterinary
- Analgesics, Opioid / administration & dosage
- Analgesics, Opioid / adverse effects
- Analgesics, Opioid / pharmacokinetics
- Analgesics, Opioid / pharmacology
- Animals
- Central Nervous System / drug effects
- Female
- Heart Rate / drug effects
- Horses
- Hot Temperature
- Male
- Meperidine / administration & dosage
- Meperidine / adverse effects
- Meperidine / analogs & derivatives
- Meperidine / blood
- Meperidine / pharmacokinetics
- Meperidine / pharmacology
- Meperidine / urine
- Nociception / drug effects
- Urticaria
Conflict of Interest Statement
Philip Kass is a member of the BMC Veterinary Research Editorial Board (Associate Editor). No other authors have any competing interests or declarations.
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Citations
This article has been cited 1 times.- Knych HK, Stucker K, Gretler SR, Kass PH, McKemie DS. Pharmacokinetics, adverse effects and effects on thermal nociception following administration of three doses of codeine to horses.. BMC Vet Res 2022 May 25;18(1):196.
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