Pharmacokinetic profiles of the novel COX-2 selective inhibitor cimicoxib in dogs.
Cimicoxib (CX) is a novel imidazole derivative that is a cyclo-oxygenase (COX)-2 selective non-steroidal anti-inflammatory drug and the latest COX-2 selective inhibitor to be released for veterinary use. Currently there is limited information available on the pharmacokinetic (PK) properties of CX. The aim of the current study was to evaluate the PK features of CX after administration of the recommended dose and after administration of a more variable dose rate in the form of the commercially available tablet. In addition, the effects of food intake on the PK properties were also evaluated. In the first study, five healthy Beagle dogs received 2mg/kg CX via the oral route following a period of fasting. The second study was conducted using six healthy Labrador retriever dogs which each received an 80 mg tablet (approximate dose 1.95-2.5mg/kg) using a crossover design, both in the fasted and fed condition. The plasma concentrations of CX were detected by a validated HPLC method. No adverse effects were observed in any dogs during the experiment. The results from the PK analysis were similar between the studies, regardless of precision of dose and fasted and fed conditions. The mean peak concentration of CX was 0.49 and 0.43 μg/mL under fasted and fed conditions, respectively. The mean half-life was about 3h after all treatments. In addition, simulated multiple dosing data revealed that time over minimal effective concentration was similar after 1.95, 2.0 and 2.5mg/kg dose administrations. These findings suggest that slight variation from the recommended dose should not alter the therapeutic outcome. In addition, CX can be administered to fed dogs without significantly affecting blood levels.
Institute of Veterinary Science, College of Veterinary Medicine, Chungnam National University, Daejeon 305-764, South Korea.
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TW
Kim
Department of Pharmacology, University of Life Sciences, Akademicka 13, 20-950 Lublin, Poland.
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Lebkowska-Wieruszewska
School of Veterinary Science, The University of Queensland, Gatton Campus, Gatton, Queensland 4343, Australia.
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Owen
Institute of Veterinary Science, College of Veterinary Medicine, Chungnam National University, Daejeon 305-764, South Korea.
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HI
Yun
Department of Pharmacology, University of Life Sciences, Akademicka 13, 20-950 Lublin, Poland.
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CJ
Kowalski
Department of Veterinary Sciences, University of Pisa, Via Livornese (lato monte) 1, San Piero a Grado, 56122 Pisa, Italy. Electronic address: mgiorgi@vet.unipi.it.
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Giorgi
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D018592:Cross-Over Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000493:pharmacokinetics*; D004285:Dogs / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007093:Imidazoles / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D013449:Sulfonamides / Q000493:pharmacokinetics*; D013607:Tablets
D052246:Cyclooxygenase 2 Inhibitors; D007093:Imidazoles; D013449:Sulfonamides; D013607:Tablets; C493522:cimicoxib
COX-2 inhibitor; Cimicoxib; Fasted; Fed; Pharmacokinetics