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Home / Equine Research Bank / Equine Vet J / Pharmacokinetics and ex vivo anti-inflammatory effects of or...
Equine veterinary journal2018; 51(3); 415-421; doi: 10.1111/evj.13024

Pharmacokinetics and ex vivo anti-inflammatory effects of oral misoprostol in horses.

Abstract: Misoprostol is an E prostanoid (EP) 2, 3 and 4 receptor agonist that is anecdotally used to treat and prevent NSAID-induced GI injury in horses. Misoprostol elicits anti-inflammatory effects in vivo in men and rodents, and inhibits TNFα production in equine leucocytes in vitro. Objective: Define the pharmacokinetic parameters of oral misoprostol in horses, and determine the inhibitory effect of oral misoprostol administration on equine leucocyte TNFα production in an ex vivo inflammation model. Methods: Pharmacokinetic study, ex vivo experimental study. Methods: Six healthy adult horses of mixed breeds were used. In phase one, horses were given 5 μg/kg misoprostol orally, and blood was collected at predetermined times for determination of misoprostol free acid (MFA) by UHPLC-MS/MS. Pharmacokinetic parameters were calculated. In phase two, horses were dosed as in phase one, and blood was collected at T0, 0.5, 1 and 4 h following misoprostol administration for leucocyte isolation. Leucocytes were stimulated with 100 ng/mL LPS, and TNFα mRNA concentrations were determined via quantitative real-time PCR. Results: About 5 μg/kg oral misoprostol produced a rapid time to maximum concentration (Tmax ) of 23.4 ± 2.4 min, with a maximum concentration (Cmax ) of 0.29 ± 0.07 ng/mL and area under the curve (AUC0-∞ ) of 0.4 ± 0.12 h ng/mL. LPS stimulation of equine leucocytes ex vivo significantly increased TNFα mRNA concentrations, and there was no significant effect of misoprostol even at the Tmax . Conclusions: Only a single dose was used, and sample size was small. Conclusions: Misoprostol is rapidly absorbed following oral administration in horses, and a single 5 μg/kg dose had no significant inhibitory effect on ex vivo LPS-stimulated TNFα mRNA production in leucocytes. Further studies analysing different dosing strategies, including repeat administration or combination with other anti-inflammatory drugs, are warranted.
© 2018 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
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Publication Date: 2018-10-23 PubMed ID: 30256450PubMed Central: PMC6587934DOI: 10.1111/evj.13024Google Scholar: Lookup
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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.

The research article discusses an experiment assessing the effects of the drug misoprostol in horses – its absorption rates and whether it inhibits inflammation in cells outside the body (ex vivo). While misoprostol was rapidly absorbed, it did not significantly reduce inflammation in this context.

Understanding Misoprostol and its Role

  • Misoprostol is a drug that acts on certain types of receptors (EP2, 3, 4) found in the body. It’s used to treat and prevent injuries in the gastrointestinal system caused by NSAIDs, a type of painkiller, in horses.
  • In humans and rodents, misoprostol is known to have anti-inflammatory effects, i.e., it reduces inflammation levels.
  • One of the strategies it employs to curb inflammation is by inhibiting the production of TNFα, a molecule produced by white blood cells during inflammation, in leucocytes or white blood cells.

Research Aim and Methodology

  • The research aimed to map the pharmacokinetic parameters of misoprostol when orally administered to horses – specifically, how the drug was absorbed, distributed, metabolized, and excreted.
  • At the same time, scientists wanted to investigate if orally taken misoprostol affected the production of inflammation-causing TNFα in equine leucocytes in an ex vivo setting, i.e., outside the equine body.
  • A total of six different healthy adult horses were involved in the research, and they were given 5 μg/kg of misoprostol orally.
  • Blood samples were collected at specific times and analyzed to measure the levels of misoprostol free acid (MFA) using a sophisticated technique called UHPLC-MS/MS.
  • Leucocytes were isolated from the blood collected at various time intervals, exposed to LPS (a powerful stimulator of the immune response), and then analyzed to understand if misoprostol inhibited the production of inflammation-causing TNFα.

Research Findings

  • The study found that misoprostol was rapidly absorbed when orally administered with a maximum concentration reached at around 23.4 ± 2.4 minutes.
  • LPS did cause an upsurge in the levels of TNFα in isolated leucocytes. Still, the presence of misoprostol did not curtail this, that is, misoprostol in these settings did not inhibit the anti-inflammatory effects.

Study Limitations and Future Research Directions

  • The researchers acknowledged several limitations to their study. The sample size was relatively small, involving only six horses, and only a single dose of misoprostol was reviewed.
  • The researchers suggested investigating alternate dosage strategies, such as repeated doses or pairing with other anti-inflammatory medications, to better gauge the drug’s effectiveness against inflammation.

Cite This Article

APA
Martin EM, Schirmer JM, Jones SL, Davis JL. (2018). Pharmacokinetics and ex vivo anti-inflammatory effects of oral misoprostol in horses. Equine Vet J, 51(3), 415-421. https://doi.org/10.1111/evj.13024

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 51
Issue: 3
Pages: 415-421

Researcher Affiliations

Martin, E M
  • North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, USA.
Schirmer, J M
  • North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, USA.
Jones, S L
  • North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, USA.
Davis, J L
  • VA-MD College of Veterinary Medicine, Blacksburg, Virginia, USA.

MeSH Terms

  • Abortifacient Agents, Nonsteroidal / administration & dosage
  • Abortifacient Agents, Nonsteroidal / pharmacokinetics
  • Administration, Oral
  • Animals
  • Area Under Curve
  • Cells, Cultured
  • Horse Diseases / drug therapy
  • Horse Diseases / metabolism
  • Horses / blood
  • Horses / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / veterinary
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Misoprostol / administration & dosage
  • Misoprostol / pharmacokinetics

Grant Funding

  • D15EQ018 / Morris Animal Foundation

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