Therapeutic drug monitoring of voriconazole.
Voriconazole is a triazole antifungal developed for the treatment of life-threatening fungal infections in immunocompromised patients. The drug, which is available for both oral and intravenous administration, has broad-spectrum activity against pathogenic yeasts, dimorphic fungi, and opportunistic molds. Voriconazole has a nonlinear pharmacokinetic profile with a wide inter- and intraindividual variety. This variability is caused by many factors such as gender, age, genotypic variation, liver dysfunction, the presence of food, and so on. Another important factor influencing voriconazole's pharmacokinetic profile is drug-drug interactions with CYP450 inhibitors as well as inducers. Variability in plasma concentrations, as a result of the previously mentioned aspects, may lead to variability in efficacy or toxicity. Determination of plasma concentrations is indicated in situations to guide dosing and to individualize and improve the treatment options resulting in better therapeutic outcome or fewer side effects. In this article, we review factors influencing voriconazole pharmacokinetic profile, the data supporting exposure-effect and exposure-toxicity relationships, review the gaps in current knowledge, which make broad recommendations for therapeutic drug monitoring difficult for voriconazole, provide the indications in which therapeutic drug monitoring is reasonable based on currently available data (eg, children), and outline the ways in which this problem could be solved. We provide a summary of the problem so that further research can be conducted to address this are of clinical need.
Brüggemann
Roger J M
RJ
Department of Clinical Pharmacy, Nijmegen University Centre for Infectious Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. r.bruggemann@akf.umcn.nl
Donnelly
J Peter
JP
Aarnoutse
Rob E
RE
Warris
Adilia
A
Blijlevens
Nicole M A
NM
Mouton
Johan W
JW
Verweij
Paul E
PE
Burger
David M
DM
D000375:Aging / Q000502:physiology; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D005838:Genotype; D006801:Humans; D017093:Liver Failure / Q000378:metabolism; D008297:Male; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051437:Renal Insufficiency / Q000378:metabolism; D012727:Sex Characteristics; D014230:Triazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole