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Influence of oxytetracycline on carprofen pharmacodynamics and pharmacokinetics in calves
Author(s) -
Brentnall C.,
Cheng Z.,
Mckellar Q. A.,
Lees P.
Publication year - 2013
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12000
Subject(s) - carprofen , pharmacokinetics , crossover study , pharmacology , chemistry , pharmacodynamics , bioavailability , medicine , placebo , alternative medicine , pathology
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 ½ k 10 ) 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 ½ 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 72 h ( P < 0.05). Inhibition of PGE 2 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.