636 AJVR, Vol 74, No. 4, April 2013 Pharmacokinetics of meloxicam in rabbits after oral administration of single and multiple doses Daniel V. Fredholm, MS, DVM; James W. Carpenter, MS, DVM; Butch KuKanich, DVM, PhD; Micah Kohles, DVM, MPA Objective—To determine the pharmacokinetics of meloxicam (1 mg/kg) in rabbits after oral administration of single and multiple doses. Animals—6 healthy rabbits. Procedures—A single dose of meloxicam (1 mg/kg, PO) was administered to the rabbits. After a 10-day washout period, meloxicam (1 mg/kg, PO) was administered to rabbits every 24 hours for 5 days. Blood samples were obtained from rabbits at predetermined intervals during both treatment periods. Plasma meloxicam concentrations were determined, and noncompartmental pharmacokinetic analysis was performed. Results—The mean peak plasma concentration and area under the plasma concentration- versus-time curve extrapolated to infinity after administration of a single dose of meloxicam were 0.83 μg/mL and 10.37 h•μg/mL, respectively. After administration of meloxicam for 5 days, the mean peak plasma concentration was 1.33 μg/mL, and the area under the plasma concentration-versus-time curve from the time of administration of the last dose to 24 hours after that time was 18.79 h•μg/mL. For single- and multiple-dose meloxicam experi- ments, the mean time to maximum plasma concentration was 6.5 and 5.8 hours and the mean terminal half-life was 6.1 and 6.7 hours, respectively. Conclusions and Clinical Relevance—Plasma concentrations of meloxicam for rabbits in the present study were proportionally higher than those previously reported for rabbits receiving 0.2 mg of meloxicam/kg and were similar to those determined for animals of other species that received clinically effective doses. A dose of 1 mg/kg may be necessary to achieve clinically effective circulating concentrations of meloxicam in rabbits, although further studies are needed. (Am J Vet Res 2013;74:636–641) Received July 1, 2012. Accepted November 6, 2012. From the Departments of Clinical Sciences (Fredholm, Carpenter) and Anatomy and Physiology (KuKanich), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506; and Ox- bow Animal Health, 29012 Mill Rd, Murdock, NE 68407 (Kohles). Dr. Fredholm’s present address is College of Veterinary Medicine, University of Florida, Gainesville, FL 32610. Supported by Oxbow Animal Health. Presented in part at the Association of Avian Veterinarians Annual Conference, Louisville, August 2012. The authors thank Katherine McInnis, Max Rinaldi, Ashley Red- mond, Robert Martinez, Amy Guernsey, and Philip Allen for assis- tance with sample analysis and manuscript preparation. Address correspondence to Dr. Fredholm (dfredholm@ufl.edu). ABBREVIATIONS AUC Area under the plasma concentration- versus time curve AUC 0–24 Area under the plasma concentration- versus time curve from administration of the last of 5 doses to 24 hours after administration of the last dose AUCinf Area under the plasma concentration- versus-time curve extrapolated to infinity after administration of a single dose Cmax Observed maximum plasma concentration COX Cyclooxygenase λz Plasma terminal rate constant Tmax Time to reach maximum plasma concentration A dequate pain management is important for animals, for both clinical and ethical reasons. Veterinary cli- nicians strive to minimize pain and distress in animals. To accomplish this goal, veterinarians should be aware of the available analgesic drugs and the biological ef- fects of such drugs in various species of animals. In companion animals, NSAIDs are commonly used for the treatment of pain. Nonsteroidal anti- inflammatory drugs have central and peripheral ac- tivities, and they effectively reduce signs of pain and inflammation in animals with musculoskeletal disease and after surgery. 1,2 Additionally, NSAIDs can be used in conjunction with other analgesic drugs (eg, opioids) for multimodal analgesia. 3,4 Meloxicam is a commonly used NSAID for animals of various species. Similar to other NSAIDs, meloxicam reduces the production of prostaglandins via inhibi- tion of the activity of COX. 5 Because meloxicam pref- erentially inhibits COX-2 in animals of most species, it may have fewer gastrointestinal tract adverse effects than other types of NSAIDs. 6 However, such adverse ef- Unauthenticated | Downloaded 09/09/22 02:37 PM UTC