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

A new interesting article has been published in Equine Vet J. 2018 Sep 26. doi: 10.1111/evj.13024. and titled:

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

Authors of this article are:
Martin EM Schirmer JM Jones SL Davis JL.

A summary of the article is shown below:
BACKGROUND: 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 humans and rodents, and inhibits TNFα production in equine leukocytes in vitro.OBJECTIVE: Define the pharmacokinetic parameters of oral misoprostol in horses, and determine the inhibitory effect of oral misoprostol administration on equine leukocyte 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 utilised. 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 hours following misoprostol administration for leukocyte isolation. Leukocytes were stimulated with 100 ng/mL LPS, and TNFα mRNA concentrations were determined via quantitative real-time PCR.RESULTS: 5 μg/kg oral misoprostol produced a rapid time to maximum concentration (Tmax ) of 23.4 ± 2.4 minutes, with a maximum concentration (Cmax ) of 0.29 ± 0.07 ng/mL, and area under the curve (AUC0-∞ ) of 0.4 ± 0.12 hr*ng/mL. LPS stimulation of equine leukocytes ex vivo significantly increased TNFα mRNA concentrations, and there was no significant effect of misoprostol even at the Tmax .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 leukocytes. Further studies analysing different dosing strategies, including repeat administration or combination with other anti-inflammatory drugs, are warranted. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.

Check out the article’s website on Pubmed for more information:

This article is a good source of information and a good way to become familiar with topics such as: E prostanoid receptor agonist;horse;inflammation;leukocyte;pharmacokinetics;tumour necrosis factor-α.

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