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

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dc.contributor.authorMartin, E. M.en
dc.contributor.authorSchirmer, J. M.en
dc.contributor.authorJones, S. L.en
dc.contributor.authorDavis, Jennifer L.en
dc.date.accessioned2021-10-14T18:50:37Zen
dc.date.available2021-10-14T18:50:37Zen
dc.date.issued2019-05en
dc.date.updated2021-10-14T18:50:36Zen
dc.description.abstractBackground: 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. Study design: 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 (T<sub>max</sub> ) of 23.4 ± 2.4 min, with a maximum concentration (C<sub>max</sub> ) of 0.29 ± 0.07 ng/mL and area under the curve (AUC<sub>0-∞</sub> ) 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 T<sub>max</sub> . Main limitations: 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.en
dc.description.versionPublished versionen
dc.format.extentPages 415-421en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1111/evj.13024en
dc.identifier.eissn2042-3306en
dc.identifier.issn0425-1644en
dc.identifier.issue3en
dc.identifier.orcidDavis, Jennifer [0000-0002-7930-4589]en
dc.identifier.otherPMC6587934en
dc.identifier.pmid30256450en
dc.identifier.urihttp://hdl.handle.net/10919/105390en
dc.identifier.volume51en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/30256450en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectE prostanoid receptor agonisten
dc.subjectHorsesen
dc.subjectinflammationen
dc.subjectleucocyteen
dc.subjectpharmacokineticsen
dc.subjecttumour necrosis factor-αen
dc.subjectVeterinary Sciencesen
dc.subject06 Biological Sciencesen
dc.subject07 Agricultural and Veterinary Sciencesen
dc.subject.meshLeukocytesen
dc.subject.meshCells, Cultureden
dc.subject.meshAnimalsen
dc.subject.meshHorsesen
dc.subject.meshHorse Diseasesen
dc.subject.meshInflammationen
dc.subject.meshAbortifacient Agents, Nonsteroidalen
dc.subject.meshMisoprostolen
dc.subject.meshAdministration, Oralen
dc.subject.meshArea Under Curveen
dc.titlePharmacokinetics and ex vivo anti-inflammatory effects of oral misoprostol in horsesen
dc.title.serialEquine Veterinary Journalen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherresearch-articleen
dc.type.otherJournal Articleen
dcterms.dateAccepted2018-09-18en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen

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