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Voriconazole increases while itraconazole decreases plasma meloxicam concentrations
V V Hynninen1, K T Olkkola, L Bertilsson
1Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Finland. vilhyn@utu.fi
Antimicrobial Agents and Chemotherapy
|November 19, 2008
Summary
Voriconazole increased meloxicam levels, while itraconazole unexpectedly decreased them, affecting meloxicam
Area of Science:
- Pharmacology
- Drug Interactions
- Clinical Pharmacy
Background:
- Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) metabolized by cytochrome P450 enzymes.
- Voriconazole and itraconazole are antifungal agents that inhibit CYP2C9 and CYP3A4, respectively.
- Understanding drug interactions is crucial for safe and effective meloxicam use.
Purpose of the Study:
- To investigate the pharmacokinetic and pharmacodynamic interactions between meloxicam and the antifungal agents voriconazole and itraconazole.
- To determine how CYP2C9 and CYP3A4 inhibition affects meloxicam's absorption, metabolism, and elimination.
- To assess the impact of these interactions on meloxicam's therapeutic efficacy.
Main Methods:
- A randomized, crossover study involving twelve healthy volunteers.
- Administration of meloxicam (15 mg) alone (control), after voriconazole pretreatment, and after itraconazole pretreatment.
- Monitoring of plasma concentrations of meloxicam, voriconazole, itraconazole, and thromboxane B(2) generation.
Main Results:
- Voriconazole significantly increased meloxicam's area under the curve (AUC) by 47% and half-life (t(1/2)) by 51%.
- Itraconazole significantly decreased meloxicam's AUC by 37% and peak concentration (C(max)) by 64%, while prolonging t(1/2).
- Reduced meloxicam plasma concentrations with itraconazole correlated with diminished inhibition of thromboxane B(2) synthesis.
Conclusions:
- Voriconazole enhances meloxicam's exposure, potentially increasing its efficacy and risk of side effects.
- Itraconazole unexpectedly reduces meloxicam exposure, possibly due to impaired absorption, leading to decreased pharmacodynamic effects.
- Clinicians should consider these significant pharmacokinetic interactions when co-prescribing meloxicam with voriconazole or itraconazole.
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