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Evaluation of the effect of fluconazole on the pharmacokinetics of cyclosporin A in healthy dogs after a single dose and at steady‐state
Author(s) -
Pieper J. B.,
Dirikolu L.,
Campbell K. L.,
Li Z.,
Mitchell M. A.
Publication year - 2017
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12352
Subject(s) - pharmacokinetics , fluconazole , crossover study , medicine , trough concentration , area under the curve , pharmacology , gastroenterology , antifungal , pathology , alternative medicine , dermatology , placebo
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 ( AUC 0‐inf. [day 1, P = 0.225], AUC tau [day 35, P = 0.225], t ½ [day 1, P = 0.279; day 35, P = 0.686], and C max [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 t ½ (CsA P = 0.042, CsA/Flu P = 0.042) over time within each group . There were no significant differences in the C max (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.