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Antimicrobial Agents and Chemotherapy, February 2009, p. 587-592, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00530-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Voriconazole Increases while Itraconazole Decreases Plasma Meloxicam Concentrations{triangledown}

V. V. Hynninen,1,2* K. T. Olkkola,2 L. Bertilsson,3 K. J. Kurkinen,4 T. Korhonen,1 P. J. Neuvonen,4 and K. Laine1,5

Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland,1 Department of Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University Hospital, Turku, Finland,2 Department of Laboratory Medicine, Division of Clinical Pharmacology at Karolinska Institute, Karolinska University Hospital, Huddinge, Stockholm, Sweden,3 Department of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland,4 TYKSLAB, Unit of Clinical Pharmacology, Turku, Finland5

Received 24 April 2008/ Returned for modification 18 September 2008/ Accepted 8 November 2008

This study investigated the effect of voriconazole, an inhibitor of cytochrome P450 2C9 (CYP2C9) and CYP3A4, and itraconazole, an inhibitor of CYP3A4, on the pharmacokinetics and pharmacodynamics of meloxicam. Twelve healthy volunteers in a crossover study ingested 15 mg of meloxicam without pretreatment (control), after voriconazole pretreatment, and after itraconazole pretreatment. The plasma concentrations of meloxicam, voriconazole, itraconazole, and thromboxane B2 (TxB2) generation were monitored. Compared to the control phase, voriconazole increased the mean area under the plasma concentration-time curve from 0 to 72 h (AUC0-72) of meloxicam by 47% (P < 0.001) and prolonged its mean half-life (t1/2) by 51% (P < 0.01), without affecting its mean peak concentration (Cmax). In contrast, itraconazole decreased the mean AUC0-72 and Cmax of meloxicam by 37% (P < 0.001) and by 64% (P < 0.001), respectively, and prolonged its t1/2 and time to Cmax. The plasma protein unbound fraction of meloxicam was unchanged by voriconazole and itraconazole. Lowered plasma meloxicam concentrations during the itraconazole phase were associated with decreased pharmacodymic effects of meloxicam, as observed by weaker inhibition of TxB2 synthesis compared to the control and voriconazole phases. Voriconazole increases plasma concentrations of meloxicam, whereas itraconazole, unexpectedly, decreases plasma meloxicam concentrations, possibly by impairing its absorption.

* Corresponding author. Mailing address: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Itäinen Pitkäkatu 4B, FIN-20520, Finland. Phone: 358 50 3624445. Fax: 358 2333 7216. E-mail: vilhyn{at}utu.fi

{triangledown} Published ahead of print on 17 November 2008.

Antimicrobial Agents and Chemotherapy, February 2009, p. 587-592, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00530-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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