Effect of itraconazole on the pharmacokinetics of diclofenac in beagle dogs.

Fahad I Al-Jenoobi

doi:10.3797/scipharm.1003-10

Abstract

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 (AUC0–∞), maximum plasma concentration (Cmax), time to reach Cmax (Tmax) and elimination half-life (t1/2), were calculated for diclofenac before and after itraconazole administration. The coadministration of itraconazole with diclofenac potassium has resulted in a significant reduction in AUC0–∞ and Cmax of diclofenac, which was about 31 and 42%; respectively. No statistically significant differences were observed for Tmax and t1/2 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 Cmax in beagle dogs.

Highlights

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties
It was noticed that the plasma concentration of diclofenac was significantly affected by the presence of itraconazole upon oral coadministration to beagle dogs
Itraconazole is a known inhibitor of CYP3A subfamily of enzymes and most of the reported pharmacokinetic interactions that are caused by this drug are believed to be mainly due to inhibition of CYP3A

Summary

Diclofenac in Beagle Dogs

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. © Al-Jenoobi; licensee Österreichische Apotheker-Verlagsgesellschaft m. b. H., Vienna, Austria. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Animal study

Assay of diclofenac in plasma

Calculation of pharmacokinetic parameters

Statistical analysis

Results and Discussion