Rev. sci. tech. Off. int. Epiz., 2007, 26 (3), 679-690 Pharmacokinetics and tissue residues of an oxytetracycline/diclofenac combination in cattle N. Mestorino (1, 2) , E. Mariño Hernández (3) , L. Marchetti (1, 4) & J.O. Errecalde (1, 2) (1) Cátedra de Farmacología, Farmacotecnia y Terapéutica, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, CC 296, 1900 La Plata, Buenos Aires, Argentina. E-mail: noram@fcv.unlp.edu.ar (2) Instituto de Ciencias Agropecuarias, Alimentarias y Ambientales (INCAM), Ruta Nacional No. 3, km 79, 1814 Cañuelas, Buenos Aires, Argentina. E-mail: jerrecal@incam.com.ar (3) Unidad de Farmacia Clínica y Farmacoterapia, Facultad de Farmacia, Universidad de Barcelona, Avenida Joan XXIII s/n, 08028 Barcelona, España (4) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Avenida Rivadavia 1917, C1033AAJ, Buenos Aires, Argentina Submitted for publication: 10 April 2006 Accepted for publication: 18 May 2007 Summary Eight male cattle were given a combined dose containing 20 mg/kg oxytetracycline and 0.5 mg/kg diclofenac intramuscularly. Blood samples were drawn at different times until 168 h after administration. Two experimental animals were slaughtered by humane means at weekly intervals up to 28 days after administration. Samples of muscle, injection zone tissue, liver, kidney and fat were obtained. Oxytetracycline and diclofenac concentrations were determined by high performance liquid chromatography. Kinetic analysis was performed by linear regression using the CSTRIP programme. Plasma oxytetracycline concentration showed a maximum (C max ) of 3.89 ± 1.48 μg/ml and a prolonged elimination half-life (T ½ : 47.73 ± 18.33 h). The diclofenac plasma profile showed high C max (577.62 ± 238.40 ng/ml), and its T ½ was also prolonged (30.48 ± 9.42 h). Oxytetracycline concentrations were measurable in liver and adipose tissue until day 21 after administration, but all tissue samples were negative for diclofenac at 21 days. The long elimination half-life of diclofenac was an unexpected finding; its T ½ in humans is 1.1 h. Keywords Antimicrobial – Cattle – Diclofenac – Non-steroidal anti-inflammatory – Oxytetracycline – Pharmacokinetics – Residue. Introduction The combination of antimicrobials and anti-inflammatory agents in therapeutics has long been considered advantageous in certain situations in human and veterinary medicine. There are few data available, however, on the pharmacokinetics and tissue residues of these drugs when applied simultaneously. Oxytetracycline (OTC) is a broad-spectrum antimicrobial agent that is active against bacteria and also against some chlamydiae, rickettsiae and protozoa. It is widely used in veterinary medicine because of its wide spectrum and advantageous pharmacokinetic features (5, 33, 39). The popularity of OTC in Latin America for treating cattle diseases prompted a review of the clinical efficacy and pharmacokinetics of OTC (29) and earlier reviews of the pharmacology of tetracyclines in general have been published (23, 25). Numerous reports have described the pharmacokinetics of OTC, including those that describe intravenous (IV) pharmacokinetic analysis using bi- and tri-compartmental models (31, 32, 45, 49).