Influence of oxytetracycline on carprofen pharmacodynamics and pharmacokinetics in calves

Brentnall, C and Cheng, Z R and McKellar, Q A and Lees, P (2013) Influence of oxytetracycline on carprofen pharmacodynamics and pharmacokinetics in calves. JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS, 36 (4). pp. 320-328.

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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 (Cmax) of S(+) carprofen in serum after co‐administration with oxytetracycline. S(+) enantiomer means for area under the serum concentration–time curve (AUC0–96h were 136.9 and 128.3 μg·h/mL and means for the terminal half‐life (T½k10) were = 12.9 and 17.3 h for carprofen alone and in combination with oxytetracycline, respectively. S(+) carprofen AUC0–96h in both carprofen treatments and T½k10 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.