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.
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