Influence of oxytetracycline on carprofen pharmacodynamics and pharmacokinetics in calves

A tissue cage model of inflammation in calves was used to determine the pharmacokinetic and pharmacodynamic properties of individual carprofen enantiomers, following the administration of the racemate. RS(±) carprofen was administered subcutaneously both alone and in combination with intramuscularly administered oxytetracycline in a four‐period crossover study. Oxytetracycline did not influence the pharmacokinetics of R(?) and S(+) carprofen enantiomers, except for a lower maximum concentration (C_max) of S(+) carprofen in serum after co‐administration with oxytetracycline. S(+) enantiomer means for area under the serum concentration–time curve (AUC_0–96h were 136.9 and 128.3 μg·h/mL and means for the terminal half‐life (T_½k₁₀) were = 12.9 and 17.3 h for carprofen alone and in combination with oxytetracycline, respectively. S(+) carprofen AUC_0–96h in both carprofen treatments and T_½k₁₀ for carprofen alone were lower (P < 0.05) than R(?) carprofen values, indicating a small degree of enantioselectivity in the disposition of the enantiomers. Carprofen inhibition of serum thromboxane B₂ ex vivo was small and significant only at a few sampling times, whereas in vivo exudate prostaglandin (PG)E₂ synthesis inhibition was greater and achieved overall significance between 36 and 72 h (P < 0.05). Inhibition of PGE₂ correlated with mean time to achieve maximum concentrations in exudate of 54 and 42 h for both carprofen treatments for R(?) and S(+) enantiomers, respectively. Carprofen reduction of zymosan‐induced intradermal swelling was not statistically significant. These data provide a basis for the rational use of carprofen with oxytetracycline in calves and indicate that no alteration to carprofen dosage is required when the drugs are co‐administered.