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

Abstract

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 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.

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.

KEY WORDS:

• Cimicoxib
• pharmacokinetics
• pharmacodynamics
• synovial fluid
• fasted/fed

Acknowledgements

Vetoquinol supplied pure analytical standards of cimicoxib, for analytical purposes. The manufacturer of the agent under review played no role in the study design nor in the collection, analysis and interpretation of data. This work was supported by a fund from Ministry of Education and Science of the Republic of Kazakhstan (0113PK0770). Other athenaeum funds (ex 60% University of Pisa and Chungnam National University) partially supported the study. Cooperlink fund (CII11A2FAV) supported the international cooperation (Ita-Kor). External funding did not support the preparation of the manuscript. Authors thank Dr H. Owen (School of Veterinary Sciences, University of Queensland, Australia) for the critical review and English editing of the manuscript.