Comparative pharmacokinetic profile of cimicoxib in dogs and cats after IV administration
| Autor: | F. Dron, M. Schneider, E. Cuinet, F. Woehrlé |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Quinidine
CYP2D6 040301 veterinary sciences Metabolite Urine Pharmacology Cimicoxib 0403 veterinary science 03 medical and health sciences chemistry.chemical_compound Dogs Pharmacokinetics Species Specificity medicine Animals Cytochrome P-450 Enzyme Inhibitors 030304 developmental biology 0303 health sciences Sulfonamides CATS General Veterinary Cyclooxygenase 2 Inhibitors Imidazoles 04 agricultural and veterinary sciences chemistry Microsome Cats Microsomes Liver Animal Science and Zoology Administration Intravenous Aryl Hydrocarbon Hydroxylases medicine.drug |
| Zdroj: | Veterinary journal (London, England : 1997). 270 |
| ISSN: | 1532-2971 |
| Popis: | Cimicoxib is a selective COX-2 inhibitor (coxib) registered for the treatment of pain and inflammation in dogs. Pharmacokinetics of some coxibs have been described in dogs and cats. In cats, total body clearance values are lower and terminal half-lives of the coxibs are longer than those in dogs. The aim of this work was to evaluate if this is also the case for cimicoxib. For this purpose, blood pharmacokinetics and urinary excretion after IV administration were compared between these species. The in vitro metabolism of cimicoxib was also evaluated using canine and feline microsomes. In canine and feline microsomes, the formation rate of demethyl-cimicoxib, a phase 1 metabolite, was decreased in presence of quinidine, a specific human cytochrome P450 (CYP)2D6 inhibitor. IC50 values were 1.6 μM and 0.056 μM with canine and feline microsomes, respectively. As quinidine was about 30 times more potent in feline microsomes, the affinity of cimicoxib to the enzyme was considered to be about 30 times lower than that in canine microsomes. Total body clearance (ClB) of cimicoxib, was 0.50 L/h kg in dogs and 0.14 L/h kg in cats (P < 0.01) and terminal half-life, T½λz, was 1.92 and 5.25 h, respectively (P < 0.01). Dose eliminated in urine was 12.2% in dogs and 3.12% in cats (P < 0.01). Conjugated demethyl-cimicoxib represented 93.7% of this amount in dogs and 67.5% in cats. Thus cimicoxib, like other veterinary coxibs, was eliminated more slowly in cats. Both CYP2D15 (the canine ortholog of CYP2D6) and UDP-glucuronyltransferase enzyme systems have reduced ability to produce metabolites of cimicoxib in cats. |
| Databáze: | OpenAIRE |
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