Pharmacokinetics and pharmacodynamics of meperidine after intramuscular and subcutaneous administration in horses.
Abstract: To describe the pharmacokinetics and pharmacodynamics of meperidine after IM and subcutaneous administration in horses. Methods: prospective, randomized, blinded, crossover trial. Methods: Six adult horses weighing 494 ± 33 kg. Methods: Treatments included meperidine 1 mg/kg IM with saline 6 mL subcutaneously, meperidine 1 mg/kg subcutaneously with saline 6 mL IM, and saline 6 mL subcutaneously and 6 mL IM, with a 7-day washout between treatments. Plasma meperidine concentrations and pharmacodynamic values (thermal and mechanical thresholds, physiological variables, fecal production) were collected at various time points for 24 hours. Accelerometry data were obtained for 8 hours to measure locomotor activity. Data were analyzed with a mixed effects model, and α was set at .05. Results: Meperidine terminal half-life (T ), maximal plasma concentrations, and time to maximal concentration were 186 ± 59 and 164 ± 56 minutes, 265.7 ± 47.2 and 243.1 ± 80.1 ng/mL at 17 ± 6, and 24 ± 13 minutes for IM at subcutaneous administration, respectively. No effect of treatment or time was observed on thermal or mechanical thresholds, heart rate, respiratory rate, locomotor activity, frequency of defecations, or fecal weight (P > .2 for all). Conclusions: Maximum meperidine concentrations were achieved quickly with a short T in both treatment groups. Neither IM nor subcutaneous meperidine influenced thermal or mechanical threshold or physiological variables. Conclusions: The short half-life and lack of detectable antinociceptive effect do not support IM or subcutaneous administration meperidine at 1 mg/kg for analgesia in horses.
© 2020 American College of Veterinary Surgeons.
Publication Date: 2020-11-26 PubMed ID: 33242227DOI: 10.1111/vsu.13545Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Randomized Controlled Trial
- Veterinary
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research investigates the efficiency and impact of two delivery methods — intramuscular (IM) and subcutaneous — of the drug meperidine in horses. The study found that neither method significantly affected the pain threshold or physiological variables in horses, with the drug having a short half-life, leading the researchers to suggest that meperidine administered at 1 mg/kg may not be effective for pain relief in horses.
Study Design
- The study was a prospective, randomized, blinded, crossover trial involving six adult horses with an average weight of 494 ± 33 kg.
- Three treatments were used – 1 mg/kg of meperidine administered through intramuscular injection with a placebo subcutaneous injection, 1 mg/kg of meperidine subcutaneously with a placebo intramuscular injection, and placebo injections both intramuscularly and subcutaneously. A break of seven days was observed between different treatment administrations (referred to as washouts).
Data Collection
- Over a 24-hour period, data such as plasma meperidine concentrations and pharmacodynamic values were collected. These pharmacodynamic values included thermal and mechanical thresholds, physiological variables such as heart and respiratory rates, fecal production, and locomotor activity, the latter measured using accelerometry for eight hours.
- The data analysis was done using a mixed effects model with a significance level (α) set at .05.
Results and Conclusions
- Meperidine’s terminal half-life, maximal plasma concentrations, and time to reach these concentrations were observed to be similar for both IM and subcutaneous administration.
- No significant effect on the horses’ thermal or mechanical thresholds, heart rate, respiratory rate, locomotor activity, or frequency of defecations was noted due to the treatments.
- The observed short half-life and lack of a detectable painkilling (antinociceptive) effect led the researchers to conclude that intramuscular or subcutaneous administration of meperidine at the dose of 1 mg/kg might not be effective in providing pain relief in horses.
Cite This Article
APA
Hanafi AL, Reed RA, Trenholme HN, Sakai DM, Ryan CA, Barletta M, Quandt JE, Knych HK.
(2020).
Pharmacokinetics and pharmacodynamics of meperidine after intramuscular and subcutaneous administration in horses.
Vet Surg, 50(2), 410-417.
https://doi.org/10.1111/vsu.13545 Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia.
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, Georgia.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia.
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, Georgia.
- K. L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California.
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California.
MeSH Terms
- Analgesics, Opioid / pharmacokinetics
- Analgesics, Opioid / pharmacology
- Animals
- Female
- Horses / metabolism
- Injections, Intramuscular / veterinary
- Injections, Subcutaneous / veterinary
- Male
- Meperidine / pharmacokinetics
- Meperidine / pharmacology
Grant Funding
- N/A / UGA For Love of the Horse Equine Endowment
References
This article includes 31 references
- Bennett RC, Steffey EP. Use of opioids for pain and anesthetic management in horses.. Vet Clin North Am Equine Pract 2002;18:47-60.
- Alexander F, Collett RA. Pethidine in the horse.. Res Vet Sci 1974;17:136-137.
- Clarke KW, Paton BS. Combined use of detomidine with opiates in the horse.. Equine Vet J 1988;20:331-334.
- Foreman JH, Ruemmler R. Efficacy of intramuscular meperidine hydrochloride versus placebo in experimental foot lameness in horses.. Equine Vet J Suppl 2013;45:48-53.
- Waterman AE, Amin A. The influence of surgery and anaesthesia on the pharmacokinetics of pethidine in the horse.. Equine Vet J Suppl 1992;11:56-58.
- Pippi NL, Lumb WV. Objective tests of analgesic drugs in ponies.. Am J Vet Res 1979;40:1082-1086.
- Clutton RE. Opioid analgesia in horses.. Vet Clin North Am Equine Pract 2010;26:493-514.
- Flacke JW, Flacke WE, Bloor BC, Van Etten AP, Kripke BJ. Histamine release by four narcotics: a double-blind study in humans.. Anesth Analg 1987;66:723-730.
- Akcasu A, Yillar DO, Akkan AG, Kuckhuseyin C. The role of mast cells in the genesis of acute manifestations following the intravenous injection of meperidine in dogs.. J Basic Clin Physiol Pharmacol 2009;20:67-72.
- Clutton RE. Unexpected responses following intravenous pethidine injection in two horses.. Equine Vet J 1987;19:72-73.
- Muir WW, Robertson JT. Visceral analgesia: effects of xylazine, butorphanol, meperidine, and pentazocine in horses.. Am J Vet Res 1985;46:2081-2084.
- Baldo BA, Pham NH. Histamine-releasing and allergenic properties of opioid analgesic drugs: resolving the two.. Anaesth Intensive Care 2012;40:216-235.
- Hamamoto-Hardman BD, Steffey EP, McKemie DS, Kass PH, Knych HK. Meperidine pharmacokinetics and effects on physiologic parameters and thermal threshold following intravenous administration of three doses to horses.. BMC Vet Res 2020;16(1):368.
- . Bioanalytical Method Validation: Guidance for Industry.. Silverspring, MD: US Food and Drug Administration and Department of Health and Human Services; 2001.
- Ranheim B, Hoiset J, Framstad T, Horsberg TE, Skaare JU, Soli NE. Pharmacokinetics of pethidine in pigs following intravenous, intramuscular and subcutaneous administration.. J Vet Pharmacol Ther 1998;21:491-493.
- Kaufman JJ, Semo NM, Koski WS. Microelectrometric titration measurement of the pKa's and partition and drug distribution coefficients of narcotics and narcotic antagonists and their pH and temperature dependence.. J Med Chem 1975;18:647-655.
- Pascoe PJ, Taylor PM. Effects of dopamine antagonists on alfentanil-induced locomotor activity in horses.. Vet Anaesth Analg 2003;30:165-171.
- Reed R, Barletta M, Mitchell K. The pharmacokinetics and pharmacodynamics of intravenous hydromorphone in horses.. Vet Anaesth Analg 2019;46:395-404.
- Reed RA, Knych HK, Barletta M. Pharmacokinetics and pharmacodynamics of hydromorphone after intravenous and intramuscular administration in horses.. Vet Anaesth Analg 2020;47:210-218.
- Wetmore LA, Pascoe PJ, Shilo-Benjamini Y, Lindsey JC. Effects of fentanyl administration on locomotor response in horses with the G57C mu-opioid receptor polymorphism.. Am J Vet Res 2016;77:828-832.
- Davis JL, Messenger KM, LaFevers DH, Barlow BM, Posner LP. Pharmacokinetics of intravenous and intramuscular buprenorphine in the horse.. J Vet Pharmacol Ther 2012;35:52-58.
- Robinson MA, Guan F, McDonnell S, Uboh CE, Soma LR. Pharmacokinetics and pharmacodynamics of dermorphin in the horse.. J Vet Pharmacol Ther 2015;38:321-329.
- Brock C, Olesen SS, Olesen AE, Frokjaer JB, Andresen T, Drewes AM. Opioid-induced bowel dysfunction: pathophysiology and management.. Drugs 2012;72:1847-1865.
- Menozzi A, Pozzoli C, Zullian C, Poli E, Serventi P, Bertini S. Inhibition of motility in isolated horse small intestine is mediated by kappa but not micro opioid receptors.. Equine Vet J 2012;44:368-370.
- Boscan P, Van Hoogmoed LM, Farver TB, Snyder JR. Evaluation of the effects of the opioid agonist morphine on gastrointestinal tract function in horses.. Am J Vet Res 2006;67:992-997.
- Donselmann Im Sande P, Hopster K, Kastner S. Effects of morphine, butorphanol and levomethadone in different doses on thermal nociceptive thresholds in horses [in German].. Tierarztl Prax Ausg G Grosstiere Nutztiere 2017;45:98-106.
- Figueiredo JP, Muir WW, Sams R. Cardiorespiratory, gastrointestinal, and analgesic effects of morphine sulfate in conscious healthy horses.. Am J Vet Res 2012;73:799-808.
- Sano H, Martin-Flores M, Santos LC, Cheetham J, Araos JD, Gleed RD. Effects of epidural morphine on gastrointestinal transit in unmedicated horses.. Vet Anaesth Analg 2011;38:121-126.
- Levionnois OL, Graubner C, Spadavecchia C. Colon constipation in horses after sustained-release buprenorphine administration.. Vet Anaesth Analg 2018;45:876-880.
- Martin-Flores M, Campoy L, Kinsley MA, Mohammed HO, Gleed RD, Cheetham J. Analgesic and gastrointestinal effects of epidural morphine in horses after laparoscopic cryptorchidectomy under general anesthesia.. Vet Anaesth Analg 2014;41:430-437.
- Andersen MS, Clark L, Dyson SJ, Newton JR. Risk factors for colic in horses after general anaesthesia for MRI or nonabdominal surgery: absence of evidence of effect from perianaesthetic morphine.. Equine Vet J 2006;38:368-374.
Citations
This article has been cited 0 times.Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists