Evaluation of the effect of fluconazole on the pharmacokinetics of cyclosporin A in healthy dogs after a single dose and at steady-state.

Abstract

The aim of the study was to describe the effect of fluconazole on the pharmacokinetics of cyclosporin A in healthy dogs when investigated as a single dose and at steady-state. Five healthy adult dogs were used in the study in a crossover design receiving either 5mg/kg of cyclosporin A (CsA) alone or 5mg/kg of fluconazole with 2.5mg/kg of cyclosporin A (CsA/Flu) for 35days. Pharmacokinetic curves were performed on day 1 and day 35 in addition to sampling trough and suspected peak concentrations (C2) twice weekly with LC/MS/MS. There was no statistically significant difference noted in any pharmacokinetic value (AUC0-inf. [day 1, P=0.225], AUCtau [day 35, P=0.225], t½ [day 1, P=0.279; day 35, P=0.686], and Cmax [day 1, P=0.225; day 35, P=0.225]) between the treatment groups by sampling day. There was a statistically significant increase in AUC (CsA P=0.043; CsA/Flu P=0.043) and t½ (CsA P=0.042, CsA/Flu P=0.042) over time within each group. There were no significant differences in the Cmax (CsA P=0.08; CsA/Flu P=0.08) when comparing day 1 vs. day 35. Steady-state cyclosporine concentrations were achieved by day 10 in both groups. Subjectively, individual variability was noted among the dogs and a much larger sample size would be beneficial in a future study.