Influence of Inflammation on Voriconazole Metabolism

ABSTRACT Voriconazole pharmacokinetics shows a large inter- and intrapatient variability. Inflammation is associated with changes in the expression of CYP isoenzymes. Here, we evaluated the influence of inflammation, marked by C-reactive protein (CRP) levels in blood, on the metabolism of voriconazole. Observational data showed an association between CRP level and the ratio of voriconazole N-oxide to voriconazole.

[1]  D. Touw,et al.  Five year results of an international proficiency testing programme for measurement of antifungal drug concentrations. , 2014, The Journal of antimicrobial chemotherapy.

[2]  E. R. van den Heuvel,et al.  Inflammation Is Associated with Voriconazole Trough Concentrations , 2014, Antimicrobial Agents and Chemotherapy.

[3]  P. G. Choe,et al.  The effect of therapeutic drug monitoring on safety and efficacy of voriconazole in invasive fungal infections: a randomized controlled trial. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[4]  A. McLachlan,et al.  Multicenter Study of Voriconazole Pharmacokinetics and Therapeutic Drug Monitoring , 2012, Antimicrobial Agents and Chemotherapy.

[5]  J. Kosterink,et al.  Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  J. Mehta,et al.  Serial Plasma Voriconazole Concentrations after Allogeneic Hematopoietic Stem Cell Transplantation , 2009, Antimicrobial Agents and Chemotherapy.

[7]  Raoul Herbrecht,et al.  Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  Micheline Piquette-Miller,et al.  Regulation of Drug-Metabolizing Enzymes and Transporters in Infection, Inflammation, and Cancer , 2008, Drug Metabolism and Disposition.

[9]  N. Wood,et al.  Pharmacokinetics and Safety of Voriconazole following Intravenous- to Oral-Dose Escalation Regimens , 2002, Antimicrobial Agents and Chemotherapy.

[10]  E. Morgan.  Regulation of cytochromes P450 during inflammation and infection. , 1997, Drug metabolism reviews.

[11]  J. Kosterink,et al.  Method for therapeutic drug monitoring of azole antifungal drugs in human serum using LC/MS/MS. , 2010, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[12]  D. Flockhart,et al.  Clinical Significance of the Cytochrome P450 2C19 Genetic Polymorphism , 2002, Clinical pharmacokinetics.