Influence of oxytetracycline on carprofen pharmacodynamics and pharmacokinetics in calves.
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.
Department of Veterinary Basic Sciences, The Royal Veterinary College, Hatfield, Herts, AL9 7TA, UK.
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Brentnall
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Cheng
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McKellar
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Lees
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002227:Carbazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002417:Cattle / Q000097:blood / Q000378:metabolism*; D018592:Cross-Over Studies; D015194:Diffusion Chambers, Culture / Q000662:veterinary; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D006207:Half-Life; D007273:Injections, Intramuscular / Q000662:veterinary; D007279:Injections, Subcutaneous / Q000662:veterinary; D008297:Male; D010118:Oxytetracycline / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors
D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D013929:Thromboxane B2; C007005:carprofen; D015232:Dinoprostone; D010118:Oxytetracycline