Pharmacokinetics of oral meloxicam in ruminant and preruminant calves R. A. MOSHER* J. F. COETZEE* ,  ,1 C. A. CULL* R. GEHRING* ,   & B. K U KANICH  , à *Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA;   PharmCATS Bioanalytical Services, K-State Research Park, Manhattan, KS, USA; à Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA Mosher, R. A., Coetzee, J. F., Cull, C. A., Gehring, R., KuKanich, B. Pharmaco kinetics of oral meloxicam in ruminant and preruminant calves. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2011.01331.x. The pharmacokinetics of oral meloxicam has been studied in ruminant, but not preruminant calves. Oral meloxicam was administered at 0.5 mg ⁄ kg to six ruminant calves via gavage (RG); to six preruminant calves via gavage (PRG); and to six preruminant calves via suckling in milk replacer (PRF). Plasma drug concentrations, determined over 120-h postadministration, were analyzed by compartmental and noncompartmental methods. The rate of drug absorption was faster (P < 0.01) in PRF (0.237 ± 0.0478 ⁄ h) than RG calves (0.0815 ± 0.0188 ⁄ h), while absorption in PRG calves (0.153 ± 0.128 ⁄ h) was not different from other groups. C max was lower (P = 0.03) in PRF (1.27 ± 0.430 lg ⁄ mL) than in PRG calves (2.20 ± 0.467 lg ⁄ mL), while C max of RG calves (1.95 ± 0.955 lg ⁄ mL) was not different from other groups. V ⁄ F was higher in PRF calves (365 ± 57 mL ⁄ kg) than either PRG (177 ± 63 mL ⁄ kg, P < 0.01) or RG (232 ± 83 mL ⁄ kg, P = 0.01) calves. These observations were likely due to differences in bioavailability, physiological maturity, and timing of the drug delivery into different compartments of the ruminant gastrointestinal tract. Results suggest that an adjustment in meloxicam dose may be necessary when administered with milk replacer. (Paper received 9 May 2011; accepted for publication 29 July 2011) Johann F. Coetzee, 111B Mosier Hall College of Veterinary Medicine Manhattan, KS, USA. E-mail: hans@coetzee.org 1 Present address: Dr. Coetzee is Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, 50011, USA. This project was supported by Agriculture and Food Research Initiative Competitive Grant no. 2008-35204-19238 and no. 2009-65120-05729 from the USDA National Institute of Food and Agriculture and Award Number T35RR007064 from the National Center For Research Resources. The absence of pain management for common surgical proce- dures, such as dehorning and castration of cattle, is considered to be an important animal welfare concern and is under consid- eration in the development of international trade agreements (Thiermann & Babcock, 2005; Phillips, 2008). Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) that is a potential candidate for use in providing pain relief to cattle. As a class, NSAIDs exert anti-inflammatory action through variable inhibition of the cyclo-oxygenase (COX) isoenzymes which are pivotal catalysts in the prostaglandin production pathway. While the expression of both COX-1 and COX-2 is constitutive and inducible, COX-2 is the isoform which is greatly upregulated in the presence of inflammatory stimuli and is therefore considered to be the desired target of NSAID activity (Lees, 2009). Although the literature is deficient with respect to cattle, meloxicam is considered to preferentially inhibit the inflammatory effects of COX-2 while tending to spare the homeostatic effects of COX-1 in humans (Warner et al., 1999), dogs (Streppa et al., 2002), cats (Giraudel et al., 2005), and horses (Beretta et al., 2005). However, the relative inhibition of the COX isoenzymes by a drug is known to vary between species; therefore, COX preference in one species does not guarantee similar preference in another (Lees, 2009). Although meloxicam is not currently approved for use in cattle in the United States, the drug has been approved for that use in the European Union as well as in countries such as Canada, New Zealand, and Australia, which are major suppliers of beef products to the US (USDA, 2009). Depending upon the country, approved indications variously include the use of meloxicam as ancillary treatment of respiratory disease, diarrhea, mastitis and ⁄ or pain because of dehorning or disbudding. Based on a dose of 0.5 mg ⁄ kg bodyweight delivered intravenously or subcutaneously, labeled J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2011.01331.x Ó 2011 Blackwell Publishing Ltd 1