Effect of Itraconazole on the Pharmacokinetics of Diclofenac in Beagle Dogs

The objective of this study was to investigate the potential effect of itraconazole on the pharmacokinetics of diclofenac potassium in beagle dogs after oral coadministration. Five male beagle dogs received a single oral 50 mg dose of diclofenac potassium alone in phase I, and along with a single oral 100 mg dose of itraconazole in phase II. Blood samples obtained for 8.0 hours post dose were analysed for diclofenac concentration using a validated high performance liquid chromatography (HPLC) assay method. The area under plasma concentration-time curve (AUC(0–∞)), maximum plasma concentration (C(max)), time to reach C(max) (T(max)) and elimination half-life (t(1/2)), were calculated for diclofenac before and after itraconazole administration. The coadministration of itraconazole with diclofenac potassium has resulted in a significant reduction in AUC(0–∞) and C(max) of diclofenac, which was about 31 and 42%; respectively. No statistically significant differences were observed for T(max) and t(1/2) of diclofenac between the two phases. Therefore, it could be concluded that oral coadministration of itraconazole may have the potential to affect the absorption of diclofenac as indicated by the significant reduction in its AUC and C(max) in beagle dogs.