title: Evaluation of pharmacokinetic and pharmacodynamic properties of cimicoxib in fasted and fed horses.
abstract: OBJECTIVE
  To determine the pharmacokinetics of cimicoxib and to assess the inhibition of cyclooxygenase (COX) after a 5 mg/kg, single oral administration in horses that were fasted or fed.
  
  
  METHODS
  The study was conducted using an open, single dose (5 mg/kg), two treatment (fasted and fed), two-period, crossover design with a 2-week interval between dosages. Six healthy mares received 5 mg/kg of cimicoxib via nasogastric tube after fasting for 12 hours, or 2 hours after feeding. After administration, blood samples were collected for up to 24 hours and plasma used for pharmacokinetic analysis. Additional serum and plasma samples were used to measure concentrations of thromboxane B2 (TXB2) and prostaglandin E2 (PGE2), to assess COX-1 and -2 inhibition, respectively.
  
  
  RESULTS
  Following cimicoxib administration, the mean maximum plasma concentration was 0.16 (SD 0.01) µg/mL and 0.14 (SD 0.03) µg/mL in fasted and fed groups, respectively. The mean time taken to reach maximum plasma concentration was longer in the fed group (5.91 (SD 3.23) hours) compared with the fasted group (3.25 (SD 1.17) hours), but this difference was not significant (p=0.12). The mean maximal inhibition of TXB2 was 62.4 (SD 13.8)% and 54.6 (SD 15.4)%, and of PGE2 was 72.1 (SD 43.3)% and 68.5 (SD 24.4)%, in fasted and fed horses, respectively.
  
  
  CONCLUSIONS
  In the present study, although the COX-2 selective action of cimicoxib was not apparent, a relatively low concentration of cimicoxib resulted in both COX-1 and -2 inhibition in horses. Further investigations are required to establish an optimal dosage regimen and safety profile before clinical trials are initiated.
authors: a College of Veterinary Medicine , Chungnam National University , 99 Daehak-ro, Yuseong-gu, Daejeon 305-764 , South Korea.
authors: T W
authors: TW
authors: Kim
authors: G
authors: G
authors: Della Rocca
authors: A
authors: A
authors: Di Salvo
authors: R
authors: R
authors: Ryschanova
authors: M
authors: M
authors: Sgorbini
authors: M
authors: M
authors: Giorgi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005508:Food Deprivation; D006207:Half-Life; D006736:Horses / Q000097:blood* / Q000378:metabolism*; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics*; D010865:Pilot Projects; D013449:Sulfonamides / Q000097:blood / Q000493:pharmacokinetics*; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D013449:Sulfonamides; D013929:Thromboxane B2; D015232:Dinoprostone; C493522:cimicoxib
keywords: Cimicoxib; fasted/fed; pharmacodynamics; pharmacokinetics; synovial fluid