Evaluation of pharmacokinetic and pharmacodynamic properties of cimicoxib in fasted and fed horses

• Published in: New Zealand veterinary journal Vol. 63; no. 2; pp. 92 - 97
• Main Authors: Kim, TW, Della Rocca, G, Di Salvo, A, Ryschanova, R, Sgorbini, M, Giorgi, M
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04.03.2015
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - blood; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Area Under Curve; blood serum; Cimicoxib; clinical trials; cross-over studies; Cyclooxygenases; Dinoprostone - antagonists & inhibitors; Dinoprostone - blood; Dose-Response Relationship, Drug; fasted/fed; fasting; Female; Food Deprivation; Half-Life; Horses; Horses - blood; Horses - metabolism; Imidazoles - blood; Imidazoles - pharmacokinetics; mares; oral administration; pharmacodynamics; Pharmacokinetics; Pilot Projects; prostaglandin synthase; prostaglandins; Sulfonamides - blood; Sulfonamides - pharmacokinetics; synovial fluid; Thromboxane B2 - antagonists & inhibitors; Thromboxane B2 - blood; pharmacokinetics; Cimicoxib; fasted/fed; pharmacodynamics; synovial fluid
• ISSN: 1176-0710; 0048-0169; 1176-0710
• DOI: 10.1080/00480169.2014.950355

AIMS: 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 B ₂ (TXB ₂) and prostaglandin E ₂ (PGE ₂), 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 TXB ₂ was 62.4 (SD 13.8)% and 54.6 (SD 15.4)%, and of PGE ₂ was 72.1 (SD 43.3)% and 68.5 (SD 24.4)%, in fasted and fed horses, respectively. CONCLUSION: 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.