Potency and selectivity of carprofen enantiomers for inhibition of bovine cyclooxygenase in whole blood assays

Whole blood in vitro assays were used to determine the potency and selectivity of carprofen enantiomers for inhibition of the isoforms of cyclooxygenase (COX), COX-1 and COX-2, in the calf. S(+)-carprofen possessed preferential activity for COX-2 inhibition but, because the slopes of inhibition curves differed, the
COX-1:COX-2 inhibition ratio decreased from 9.04:1 for inhibitory concentration (IC)₁₀ to 1.84:1 for IC₉₅. R() carprofen inhibited COX-2 preferentially only for low inhibition of the COX isoforms (IC₁₀ COX-1:COX-2 = 6.63:1), whereas inhibition was preferential for COX-1 for a high level of inhibition (IC95
COX-1:COX-2 = 0.20:1). S(+) carprofen was the more potent inhibitor of COX isoforms; potency ratios S(+):R() carprofen were 11.6:1 for IC₁₀ and 218:1 for IC₉₀. Based on serum concentrations of carprofen enantiomers obtained after administration of a therapeutic dose of 1.4 mg/kg to calves subcutaneously,
S(+)-carprofen concentrations exceeded the in vitro IC₈₀ COX-2 value for 32 h and the IC₂₀ for COX-1 for 33 h. The findings are discussed in relation to efficacy and safety of carprofen in calves.