Influence of oxytetracycline on carprofen pharmacodynamics and pharmacokinetics in calves.

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 (AUC0-96 h were 136.9 and 128.3 μg·h/mL and means for the terminal half-life (T(1/2) k10 ) were = 12.9 and 17.3 h for carprofen alone and in combination with oxytetracycline, respectively. S(+) carprofen AUC0-96 h in both carprofen treatments and T(1/2) k10 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.

• Authors: C Brentnall, Z Cheng, Q A McKellar, P Lees
• Journal: Journal of veterinary pharmacology and therapeutics (J Vet Pharmacol Ther) Vol. 36 Issue 4 Pg. 320-8 (Aug 2013) ISSN: 1365-2885 [Electronic] England
• PMID: 22913421 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 John Wiley & Sons Ltd.

Chemical References

• Anti-Bacterial Agents
• Anti-Inflammatory Agents, Non-Steroidal
• Carbazoles
• Thromboxane B2
• carprofen
• Dinoprostone
• Oxytetracycline

Topics

• Animals
• Anti-Bacterial Agents (administration & dosage, blood, pharmacology)
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, blood, pharmacokinetics)
• Area Under Curve
• Carbazoles (administration & dosage, blood, pharmacokinetics)
• Cattle (blood, 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, blood, pharmacology)
• Thromboxane B2 (antagonists & inhibitors)