title: 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 5 mg/kg of cyclosporin A (CsA) alone or 5 mg/kg of fluconazole with 2.5 mg/kg of cyclosporin A (CsA/Flu) for 35 days. 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.
authors: Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL, USA.
authors: J B
authors: JB
authors: Pieper
authors: Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, LA, USA.
authors: L
authors: L
authors: Dirikolu
authors: Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL, USA.
authors: K L
authors: KL
authors: Campbell
authors: Metabolomics Center of Roy J. Carver Biotechnology Center, University of Illinois, Urbana, IL, USA.
authors: Z
authors: Z
authors: Li
authors: Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL, USA.
authors: M A
authors: MA
authors: Mitchell
mesh_terms: D000818:Animals; D019540:Area Under Curve; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004285:Dogs; D015725:Fluconazole / Q000494:pharmacology*; D007166:Immunosuppressive Agents; D053719:Tandem Mass Spectrometry
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D015725:Fluconazole