title: The pharmacokinetics and in vitro/ex vivo cyclooxygenase selectivity of parecoxib and its active metabolite valdecoxib in cats.
abstract: Parecoxib (PX) is an injectable prodrug of valdecoxib (VX, which is a selective cyclo-oxyganase-2 (COX-2)) inhibitor licensed for humans. The aim of the present study was to evaluate pharmacokinetics and in vitro/ex vivo cyclooxygenase selectivity of PX and VX in cats. In a whole blood in vitro study, PX did not affect either COX enzymes whereas VX revealed a COX-2 selective inhibitory effect in feline whole blood. The IC50 values of VX for COX-2 and COX-1 were 0.45 and 38.6 µM, respectively. Six male cats were treated with 2.5 mg/kg of PX by intramuscular injection. PX was rapidly converted to VX with a relatively short half-life of 0.4 h. VX achieved peak plasma concentration (2.79 ± 1.59 µg/mL) at 7 h following PX injection. The mean residence times for PX and VX were 0.43 ± 0.15 and 5.94 ± 0.88 h, respectively. In the ex vivo study, PX showed a COX-2 inhibition rate of about 70% in samples taken at 1, 2, 4 and 10 h after injection, with a significant difference compared to the control. In contrast, COX-1 was slightly inhibited, ranging from 0.7% to 9.7% of the control inhibition rate without any significant difference for 24 h after PX administration. The preliminary findings of the present research appear promising and encourage further studies to investigate whether PX can be successfully used in feline medicine.
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon, South Korea.
authors.forename: T W
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Department of Veterinary Sciences, Division of Pharmacology & Toxicology, University of Turin, Via L. da Vinci 44, 10095 Grugliasco, Torino, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Vercelli
authors.affiliation: Department of Veterinary Sciences, University of Pisa, Via Livornese (lato monte) 1, 56122 San Piero a Grado, Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Department of Veterinary Sciences, Division of Pharmacology & Toxicology, University of Turin, Via L. da Vinci 44, 10095 Grugliasco, Torino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Re
authors.affiliation: Department of Veterinary Sciences, University of Pisa, Via Livornese (lato monte) 1, 56122 San Piero a Grado, Pisa, Italy. Electronic address: mgiorgi@vet.unipi.it.
authors.forename: M
authors.initials: M
authors.lastname: Giorgi
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002415:Cats / Q000097:blood / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D007555:Isoxazoles / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D013449:Sulfonamides / Q000097:blood* / Q000378:metabolism; D000096926:Benzenesulfonamides
chemical_list: D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles; D013449:Sulfonamides; C406224:valdecoxib; D000096926:Benzenesulfonamides; C409945:parecoxib
keywords: COX-1 and COX-2; Cat; Parecoxib; Selectivity; Valdecoxib