2018 journal article

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

EQUINE VETERINARY JOURNAL, 51(3), 415–421.

By: E. Martin  n, J. Schirmer n, S. Jones n  & J. Davis *

author keywords: horse; leucocyte; E prostanoid receptor agonist; pharmacokinetics; inflammation; tumour necrosis factor-
MeSH headings : 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
TL;DR: 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. (via Semantic Scholar)
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3. Good Health and Well-being (Web of Science; OpenAlex)
5. Gender Equality (Web of Science)
Source: Web Of Science
Added: May 6, 2019

SummaryBackgroundMisoprostol 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.ObjectiveDefine 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 designPharmacokinetic study, ex vivo experimental study.MethodsSix 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.ResultsAbout 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.Main limitationsOnly a single dose was used, and sample size was small.ConclusionsMisoprostol 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.