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Journal of veterinary pharmacology and therapeutics2014; 38(4); 365-374; doi: 10.1111/jvp.12191

Pharmacokinetics and pharmacodynamics comparison between subcutaneous and intravenous butorphanol administration in horses.

Abstract: The study objective was to compare butorphanol pharmacokinetics and physiologic effects following intravenous and subcutaneous administration in horses. Ten adult horses received 0.1 mg/kg butorphanol by either intravenous or subcutaneous injections, in a randomized crossover design. Plasma concentrations of butorphanol were measured at predetermined time points using highly sensitive liquid chromatography-tandem mass spectrometry assay (LC-MS/MS). Demeanor and physiologic variables were recorded. Data were analyzed with multivariate mixed-effect model on ranks (P ≤ 0.05). For subcutaneous injection, absorption half-life and peak plasma concentration of butorphanol were 0.10 ± 0.07 h and 88 ± 37.4 ng/mL (mean ± SD), respectively. Bioavailability was 87%. After intravenous injection, mean ± SD butorphanol steady-state volume of distribution and clearance was 1.2 ± 0.96 L/kg and 0.65 ± 0.20 L/kg/h, respectively. Terminal half-lives for butorphanol were 2.31 ± 1.74 h and 5.29 ± 1.72 h after intravenous and subcutaneous administrations. Subcutaneous butorphanol reached and maintained target plasma concentrations >10 ng/mL for 2 ± 0.87 h (Mean ± SD), with less marked physiologic and behavioral effects compared to intravenous injection. Subcutaneous butorphanol administration is an acceptable alternative to the intravenous route in adult horses.
Publication Date: 2014-12-07 PubMed ID: 25484250DOI: 10.1111/jvp.12191Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Research Support
  • Non-U.S. Gov't

Summary

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This research investigates the differences in drug absorption and effects between injecting butorphanol subcutaneously (under the skin) and intravenously (into the vein) in horses. The results showed that subcutaneous administration allows the drug to maintain effective blood concentration for longer, with less impact on behavior and physiology compared to intravenous injection, presenting it as a viable alternative method of drug delivery in horses.

Study Design and Procedure

  • The goal of the study was to examine how butorphanol, a pain-relieving medication, is absorbed and processed by the body when it’s administered via two different routes – intravenously and subcutaneously – in horses.
  • Using a randomized crossover design, ten adult horses received 0.1 mg/kg of butorphanol either via an intravenous injection directly into the vein or a subcutaneous injection beneath the skin.
  • The levels of butorphanol in the blood were measured at predetermined times using a precise scientific method called liquid chromatography-tandem mass spectrometry (LC-MS/MS).
  • The demeanor, or behavior, of the horses and physiological parameters were also recorded during the study.
  • Data were statistically analyzed using a multivariate mixed-effect model on ranks.

Key Findings

  • The findings reveal that the absorption half-life and peak plasma concentration of butorphanol after a subcutaneous injection were relatively short and stable.
  • Subcutaneously administered butorphanol had a bioavailability of 87%, showing that a significant proportion of the drug was effectively absorbed into the body.
  • After intravenous injection, the butorphanol steady-state volume of distribution and clearance, which represent the drug’s dispersion and elimination from the body respectively, were noted.
  • The terminal half-life for butorphanol, which represents how long the drug takes to reduce to half its initial concentration, was longer for subcutaneous administration than for intravenous administration.
  • The plasma levels of butorphanol remained above therapeutical concentration for a longer time with subcutaneous administration compared to intravenous administration, showing its capability for extended relief.
  • The physiological and behavioral effects of the drug were also less pronounced with subcutaneous injection.

Conclusions

  • Based on these findings, it was concluded that subcutaneous administration of butorphanol was a suitable alternative to intravenous administration in adult horses.
  • The less marked physiological and behavioral effects combined with superior sustained therapeutic plasma levels highlight the potential advantages of subcutaneous administration.

Cite This Article

APA
Chiavaccini L, Claude AK, Lee JH, Ross MK, Meyer RE, Langston VC. (2014). Pharmacokinetics and pharmacodynamics comparison between subcutaneous and intravenous butorphanol administration in horses. J Vet Pharmacol Ther, 38(4), 365-374. https://doi.org/10.1111/jvp.12191

Publication

ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 38
Issue: 4
Pages: 365-374

Researcher Affiliations

Chiavaccini, L
  • Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
Claude, A K
  • Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
Lee, J H
  • Department of Basic Sciences, Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
Ross, M K
  • Department of Basic Sciences, Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
Meyer, R E
  • Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
Langston, V C
  • Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.

MeSH Terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / blood
  • Analgesics, Opioid / pharmacokinetics
  • Animals
  • Biological Availability
  • Butorphanol / administration & dosage
  • Butorphanol / blood
  • Butorphanol / pharmacokinetics
  • Cross-Over Studies
  • Female
  • Half-Life
  • Horses / blood
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Male
  • Statistics as Topic

Citations

This article has been cited 5 times.
  1. Ebner L, O O, Simon B, Lizarraga I, Smith J, Cox S. Pharmacokinetics of butorphanol following intravenous and intramuscular administration in donkeys: A preliminary study. Front Vet Sci 2022;9:979794.
    doi: 10.3389/fvets.2022.979794pubmed: 36213418google scholar: lookup
  2. Nannarone S, Giannettoni G, Laurenza C, Giontella A, Moretti G. Methadone or Butorphanol as Pre-Anaesthetic Agents Combined with Romifidine in Horses Undergoing Elective Surgery: Qualitative Assessment of Sedation and Induction. Animals (Basel) 2021 Aug 31;11(9).
    doi: 10.3390/ani11092572pubmed: 34573538google scholar: lookup
  3. Straticò P, Carluccio A, Varasano V, Guerri G, Suriano R, Robbe D, Cerasoli I, Petrizzi L. Analgesic Effect of Butorphanol during Castration in Donkeys under Total Intravenous Anaesthesia. Animals (Basel) 2021 Aug 9;11(8).
    doi: 10.3390/ani11082346pubmed: 34438803google scholar: lookup
  4. Del Vecchio G, Labuz D, Temp J, Seitz V, Kloner M, Negrete R, Rodriguez-Gaztelumendi A, Weber M, Machelska H, Stein C. pK(a) of opioid ligands as a discriminating factor for side effects. Sci Rep 2019 Dec 18;9(1):19344.
    doi: 10.1038/s41598-019-55886-1pubmed: 31852967google scholar: lookup
  5. Di Cesare F, Rabbogliatti V, Draghi S, Amari M, Brioschi FA, Villa R, Ravasio G, Cagnardi P. Pharmacokinetics of dexmedetomidine in anaesthetized horses following repeated subcutaneous administration and intravenous constant rate infusion. BMC Vet Res 2023 Dec 9;19(1):264.
    doi: 10.1186/s12917-023-03831-wpubmed: 38071301google scholar: lookup