EVALUATION OF PHARMACOKINETIC AND PHARMACODYNAMIC PROPERTIES OF CIMICOXIB IN FASTED AND FED HORSES

Aims: The present study was performed in order to better understand the pharmacokinetic features of cimicoxib and to assess the cyclooxygenase (COX) inhibition rate after a 5 mg/kg, single oral administration in horses. Methods: The study was conducted using an open, single-dose (intra-gastrically at 5 mg/kg), two treatment (fasted and fed), two-period, crossover design (n=6) with a 2 week interval between dosages. After administration, blood samples were collected and subjected to pharmacokinetic and ex vivo pharmacodynamic studies. For the ex vivo study, the serum levels of thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were measured to assess COX-1 and -2 inhibition, respectively, using an ELISA kit. 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). In the ex vivo pharmacodynamic assay, the mean maximal inhibition rate of TXB2 and PGE2 was about 60% and 70% respectively, in both fasted and fed groups. 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.