Influence of oxytetracycline on carprofen pharmacodynamics and pharmacokinetics in calves

Brentnall, C; Cheng, Z R; 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.

Citation

Brentnall, C., Cheng, Z. R., McKellar, Q. A., & Lees, P. (2013). Influence of oxytetracycline on carprofen pharmacodynamics and pharmacokinetics in calves. Journal of Veterinary Pharmacology and Therapeutics, 36(4), 320-328. https://doi.org/10.1111/jvp.12000

• Journal Article Type: Article
• Acceptance Date: Jul 23, 2012
• Publication Date: Jul 5, 2013
• Deposit Date: Nov 11, 2014
• Journal: Journal of Veterinary Pharmacology and Therapeutics
• Print ISSN: 0140-7783
• Electronic ISSN: 1365-2885
• Publisher: American Academy of Veterinary Pharmacology and Therapeutics
• Peer Reviewed: Peer Reviewed
• Volume: 36
• Issue: 4
• Pages: 320-328
• DOI: https://doi.org/10.1111/jvp.12000
• Public URL: https://rvc-repository.worktribe.com/output/1409089
• Additional Information: Corporate Creators : Hertfordshire