Single-dose pharmacokinetics of orally and rectally administered misoprostol in adult horses

Christine T. Lopp 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802

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Annette M. McCoy 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802

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Dawn Boothe 2Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849

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David J. Schaeffer 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802

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Kara Lascola 2Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849

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Abstract

OBJECTIVE

To characterize the pharmacokinetics of a clinically relevant dose of misoprostol administered PO or per rectum (PR) to horses.

ANIMALS

8 healthy adult horses.

PROCEDURES

In a randomized 3-way crossover design, horses received a single dose of misoprostol (5 μg/kg) administered PO (with horses fed and unfed) and PR, with a minimum 3-week washout period separating the experimental conditions. Blood samples were obtained before and at various points after drug administration (total, 24 hours), and plasma concentrations of misoprostol free acid were measured.

RESULTS

Mean maximum plasma concentration of misoprostol was significantly higher in the PR condition (mean ± SD, 967 ± 492 pg/mL) and unfed PO condition (655 ± 259 pg/mL) than in the fed PO condition (352 ± 109 pg/mL). Mean area under the concentration-versus-time curve was significantly lower in the PR condition (219 ± 131 pg•h/mL) than in the unfed (1,072 ± 360 pg•h/mL) and fed (518 ± 301 pg•h/mL) PO conditions. Mean time to maximum concentration was ≤ 30 minutes for all conditions. Mean disappearance half-life was shortest in the PR condition (21 ± 29 minutes), compared with values for the unfed (170 ± 129 minutes) and fed (119 ± 51 minutes) PO conditions. No adverse effects were noted.

CONCLUSIONS AND CLINICAL RELEVANCE

Misoprostol was rapidly absorbed and eliminated regardless of whether administered PO or PR to horses. Rectal administration may be a viable alternative for horses that cannot receive misoprostol PO, but this route may require more frequent administration to maintain therapeutic drug concentrations.

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