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Oral voriconazole and miconazole oral gel produce comparable effects on the pharmacokinetics and pharmacodynamics of etoricoxib

  • Pharmacokinetics and Disposition
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Abstract

Purpose

The effect of topical miconazole oral gel and systemic oral voriconazole on the pharmacokinetics of oral etoricoxib was studied in 12 healthy volunteers.

Methods

Plasma concentrations of etoricoxib, miconazole, voriconazole, and thromboxane B2 generation were followed after ingestion of 60 mg etoricoxib without pretreatment, after topical administration of miconazole oral gel (85 mg × 3, 3 days), or after oral voriconazole (400 mg × 2, 1st day, 200 mg × 2, 2nd day).

Results

Etoricoxib area under the plasma concentration-time curve \(\left( {{\text{AUC}}_{0 - \infty } } \right)\) and maximum plasma concentration (Cmax) geometric mean ratios (GMR) with/without miconazole were 1.69 {90% confidence interval (CI); 1.46–1.92} and 1.12 (90% CI; 0.99–1.25), respectively, and corresponding GMRs with/without voriconazole were 1.49 (90% CI; 1.37–1.61) and 1.19 (90% CI; 1.08–1.31), respectively.

Conclusions

Miconazole oral gel and oral voriconazole produced comparable increase in the exposure to etoricoxib, presumably via CYP3A inhibition.

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Acknowledgments

This work was supported by Turku University Hospital research fund EVO 13390 (Laine) EVO 13821 (Olkkola). Mr. Tero Vahlberg is thanked for his assistance in statistical issues. Mrs. Elina Kahra is thanked for her skilful assistance in organizing the study.

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Authors and Affiliations

  1. Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Itäinen Pitkäkatu 4B, 20520, Turku, Finland

    Ville V. Hynninen & Kari Laine

  2. Department of Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University Hospital, Kiinanmyllynkatu 4–8, 20520, Turku, Finland

    Klaus T. Olkkola

  3. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 4, 00290, Helsinki, Finland

    Pertti J. Neuvonen

Authors
  1. Ville V. Hynninen
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  2. Klaus T. Olkkola
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  3. Pertti J. Neuvonen
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  4. Kari Laine
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Correspondence to Ville V. Hynninen.

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Hynninen, V.V., Olkkola, K.T., Neuvonen, P.J. et al. Oral voriconazole and miconazole oral gel produce comparable effects on the pharmacokinetics and pharmacodynamics of etoricoxib. Eur J Clin Pharmacol 65, 89–95 (2009). https://doi.org/10.1007/s00228-008-0556-9

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  • DOI: https://doi.org/10.1007/s00228-008-0556-9

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