Effects of a single dose of orally and rectally administered misoprostol in an in vivo endotoxemia model in healthy adult horses.

Autor:	Kimura S; Department of Clinical Sciences, Auburn University, Auburn, AL., McCoy AM; Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL., Boothe DM; Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL., Wooldridge AA; Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, AL., Graff E; Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL., Hammack SM; Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL., Cresci L; Department of Clinical Sciences, Auburn University, Auburn, AL., Hofmeister E; Department of Clinical Sciences, Auburn University, Auburn, AL., Lascola KM; Department of Clinical Sciences, Auburn University, Auburn, AL.
Jazyk:	angličtina
Zdroj:	American journal of veterinary research [Am J Vet Res] 2022 Jun 20; Vol. 83 (8). Date of Electronic Publication: 2022 Jun 20.
DOI:	10.2460/ajvr.21.12.0206
Abstrakt:	Objective: To describe misoprostol pharmacokinetics and anti-inflammatory efficacy when administered orally or per rectum in endotoxin-challenged horses. Animals: 6 healthy geldings. Procedures: A randomized 3-treatment crossover design was performed with a minimum washout period of 28 days between treatment arms. Prior to endotoxin challenge (lipopolysaccharide, 30 ng/kg IV over 30 minutes), horses received misoprostol (5 µg/kg once) per os (M-PO) or per rectum (M-PR) or water as control (CON). Clinical parameters were evaluated and blood samples obtained to measure plasma misoprostol free acid concentration, leukocyte counts, and tumor necrosis factor-α (TNFα) and interleukin 6 (IL-6) leukocyte gene expression and serum concentrations. Results: In the M-PO treatment arm, maximum plasma concentration and area under the concentration-versus-time curve (mean ± SD) were higher (5,209 ± 3,487 pg/mL and 17,998,254 ± 13,194,420 h·pg/mL, respectively) and median (interquartile range) time to maximum concentration (25 min [18 to 34 min]) was longer than in the M-PR treatment arm (854 ± 855 pg/mL; 644,960 ± 558,866 h·pg/mL; 3 min [3 to 3.5 min]). Significant differences in clinical parameters, leukocyte counts, and TNFα or IL-6 gene expression or serum protein concentration were not detected. Downregulation of relative gene expression was appreciated for individual horses in the M-PO and M-PR treatment arms at select time points. Clinical Relevance: Considerable variability in measured parameters was detected among horses within and between treatment arms. Misoprostol absorption and systemic exposure after PO administration differed from previous reports in horses not administered LPS. Investigation of multidose administration of misoprostol is warranted to better evaluate efficacy as an anti-inflammatory therapeutic.
Databáze:	MEDLINE
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