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

Jason Bradley Pieper, L. Dirikolu, K. L. Campbell, Zhong (Lucas) Li, M. A. Mitchell

Research output: Contribution to journalArticle

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 (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.

Original languageEnglish (US)
Pages (from-to)304-308
Number of pages5
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume40
Issue number3
DOIs
StatePublished - Jun 2017

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fluconazole
cyclosporine
Fluconazole
Cyclosporine
pharmacokinetics
Pharmacokinetics
Dogs
dogs
dosage
influenza
Area Under Curve
sampling
Sample Size
Cross-Over Studies

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

Cite this

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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 (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.",
author = "Pieper, {Jason Bradley} and L. Dirikolu and Campbell, {K. L.} and Li, {Zhong (Lucas)} and Mitchell, {M. A.}",
year = "2017",
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T1 - Evaluation of the effect of fluconazole on the pharmacokinetics of cyclosporin A in healthy dogs after a single dose and at steady-state

AU - Pieper, Jason Bradley

AU - Dirikolu, L.

AU - Campbell, K. L.

AU - Li, Zhong (Lucas)

AU - Mitchell, M. A.

PY - 2017/6

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N2 - 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.

AB - 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.

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