AJVR, Vol 71, No. 7, July 2010 831 T herapeutic immune suppression via administration of steroidal anti-inflammatory medications is nec- essary for a variety of conditions in horses, including recurrent airway obstruction (ie, heaves), interstitial pneumonia, immune-mediated diseases, hypersensitiv- ity reactions, and inflammatory airway disease. Treat- ment for these conditions is typically initiated with IV administration of glucocorticoids and subsequently modified to a lower dose of PO administered medica- tion, which may be continued for a period of several days to weeks until it is gradually discontinued by use of tapering doses. Although preparations of glucocorti- Pharmacokinetics and pharmacodynamics of dexamethasone after oral administration in apparently healthy horses Jason A. Grady, DVM, MS; Elizabeth G. Davis, DVM, PhD; Butch KuKanich, DVM, PhD; Amanda B. Sherck, DVM Objective—To assess pharmacokinetic and pharmacodynamic properties of dexametha- sone administered PO as a solution or powder, compared with properties of dexametha- sone solution administered IV, in apparently healthy horses. Animals—6 adult horses. Procedures—Serum cortisol concentration for each horse was determined before each treatment (baseline values). Dexamethasone (0.05 mg/kg) was administered PO (in solution or powdered form) or IV (solution) to horses from which feed had or had not been withheld (unfed and fed horses, respectively). Each horse received all 6 treatments in random order at 2-week intervals; PO and IV administrations of dexamethasone were accompanied by IV or PO sham treatments, respectively. Plasma dexamethasone and serum cortisol concen- trations were assessed at predetermined intervals. Results—Maximum plasma dexamethasone concentration after PO administration of pow- dered dexamethasone in unfed horses was significantly higher than the maximum plasma concentration after PO administration of dexamethasone solution in unfed or fed horses. Mean bioavailability of dexamethasone ranged from 28% to 66% but was not significantly different among horses receiving either formulation PO in the unfed or fed state. After dexa- methasone treatment PO or IV, serum cortisol concentrations were significantly less than baseline at 1 to 72 hours in unfed horses and at 2 to 48 hours in fed horses. Conclusions and Clinical Relevance—PO or IV administration of dexamethasone resulted in suppression of cortisol secretion in unfed and fed adult horses; the magnitude of sup- pression did not differ among treatment groups, and serum cortisol concentrations returned to baseline after 48 to 72 hours. (Am J Vet Res 2010;71:831–839) coids for PO administration are commercially produced and approved by the FDA for human or veterinary use, the use of such products may not be economically fea- sible or the products may not be readily available or efficacious. For example, the FDA-approved pow- dered formulation of dexamethasone a is difficult to ob- Received April 15, 2009. Accepted May 15, 2009. From the Veterinary Medical Teaching Hospital (Grady, Davis, Sherck) and Department of Anatomy and Physiology (KuKanich), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506. Dr. Grady’s present address is Sapulpa Equine Hospital, 12226 Heywood Hill Rd, Sapulpa, OK 74066. Supported by the Kansas State University Mentored Clinical, Applied or Translational Research Grant and the Kansas Horse Racing Com- mission. Presented in abstract form at the American College of Veterinary In- ternal Medicine Conference, Seattle, June 2007. Address correspondence to Dr. Grady (dr.grady@sapulpaequine. com). ABBREVIATIONS AUC Area under the plasma concentration- versus-time curve AUC 0–∞ Area under the plasma concentration- versus-time curve from time 0 to infinity C max Maximum plasma concentration of dexamethasone IS Internal standard LC Liquid chromatography LC-MS Liquid chromatography–mass spectrometry MRT Mean residence time PPID Pituitary pars intermedia dysfunction t ½λz Terminal half-life T max Time to maximal measured plasma dexamethasone concentration Vd ss Volume of distribution at steady state Unauthenticated | Downloaded 08/20/22 11:46 PM UTC