Influence of oxytetracycline on carprofen pharmacodynamics and pharmacokinetics in calves

• Published in: Journal of veterinary pharmacology and therapeutics Vol. 36; no. 4; pp. 320 - 328
• Main Authors: Brentnall, C., Cheng, Z., Mckellar, Q. A., Lees, P.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-08-2013
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - blood; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Area Under Curve; Carbazoles - administration & dosage; Carbazoles - blood; Carbazoles - pharmacokinetics; Cattle - blood; Cattle - metabolism; Cross-Over Studies; Diffusion Chambers, Culture - veterinary; Dinoprostone - antagonists & inhibitors; Drug Interactions; Half-Life; Injections, Intramuscular - veterinary; Injections, Subcutaneous - veterinary; Male; Oxytetracycline - administration & dosage; Oxytetracycline - blood; Oxytetracycline - pharmacology; Thromboxane B2 - antagonists & inhibitors
• ISSN: 0140-7783; 1365-2885
• DOI: 10.1111/jvp.12000

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.