Co‐formulation of ketoprofen with tulathromycin alters pharmacokinetic and pharmacodynamic profile of ketoprofen in cattle

The current studies aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profile and to establish a PK‐PD model for ketoprofen in a new fixed combination product containing tulathromycin (2.5 mg/kg) and ketoprofen (3 mg/kg) to treat bovine respiratory disease associated with pyrexia i...

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Bibliographic Details
Published inJournal of veterinary pharmacology and therapeutics Vol. 45; no. 1; pp. 69 - 82
Main Authors De Koster, Jenne, Boucher, Joseph F., Tena, Jezaniah‐Kira, Gehring, Ronette, Stegemann, Michael R.
Format Journal Article
LanguageEnglish
Published England 01.01.2022
Subjects
3Rs
Animals
Cattle
Cattle Diseases
Disaccharides
Heterocyclic Compounds
Ketoprofen
pharmacodynamics
pharmacokinetics
ketoprofen
pharmacokinetics
cattle
3Rs
pharmacodynamics
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Summary:The current studies aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profile and to establish a PK‐PD model for ketoprofen in a new fixed combination product containing tulathromycin (2.5 mg/kg) and ketoprofen (3 mg/kg) to treat bovine respiratory disease associated with pyrexia in cattle. Firstly, the effect of different ketoprofen doses as mono‐substance (1, 3, and 6 mg/kg subcutaneous) on lipopolysaccharide‐induced fever was evaluated which indicated that rectal temperature reduction lasted longer in the calves receiving 3 and 6 mg/kg ketoprofen. Secondly, the PK profile of the combination product was compared with mono‐substance products (3 mg/kg subcutaneous and intramuscular). The PK profile of ketoprofen in the combination product was characterized by longer t1/2, lower Cmax and increased AUC in comparison with mono‐substance products. Due to prolonged ketoprofen exposure in the combination product, the pyrexia reducing effect of the combination product lasted longer in a second lipopolysaccharide challenge study in comparison with mono‐substance products. Finally, a PK‐PD model for the anti‐pyretic effect of ketoprofen was developed based on the data from the different studies. The PK‐PD model eliminated the need for additional animal experiments and indicated that a 3 mg/kg ketoprofen dose in the combination product provided optimal efficacy.
ISSN:0140-7783
1365-2885
DOI:10.1111/jvp.12999