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- Title
Influence of oxytetracycline on carprofen pharmacodynamics and pharmacokinetics in calves.
- Authors
Brentnall, C.; Cheng, Z.; Mckellar, Q. A.; Lees, P.
- Abstract
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.
- Subjects
EFFECT of drugs on cattle; OXYTETRACYCLINE; CARPROFEN; PHARMACODYNAMICS; ENANTIOMERS
- Publication
Journal of Veterinary Pharmacology & Therapeutics, 2013, Vol 36, Issue 4, p320
- ISSN
0140-7783
- Publication type
Article
- DOI
10.1111/jvp.12000