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 128.3gh/mL and means for the terminal half-life (T(1/2)k(10)) were=12.9 and 17.3h for carprofen alone and in combination with oxytetracycline, respectively. S(+) carprofen AUC(0-96h) in both carprofen treatments and T(1/2)k(10) 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 B(2)ex vivo was small and significant only at a few sampling times, whereas in vivo exudate prostaglandin (PG)E-2 synthesis inhibition was greater and achieved overall significance between 36 and 72h (P<0.05). Inhibition of PGE(2) correlated with mean time to achieve maximum concentrations in exudate of 54 and 42h 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.