Therapeutic Drug Monitoring of Voriconazole and Posaconazole

Abstract

Despite the availability of newer antifungal agents, invasive fungal diseases remain a leading cause of morbidity and mortality in immunocompromised patients. Voriconazole and posaconazole are two extended-spectrum triazoles indicated for treatment and prophylaxis of invasive fungal diseases. Recently, there has been increased interest in the utility of therapeutic drug monitoring to optimize safety and efficacy of antifungals in an attempt to improve patient outcomes. We reviewed the pharmacokinetic and pharmacodynamic characteristics of voriconazole and posaconazole in the context of clinical indications for therapeutic drug monitoring. In addition, the most recent evidence examining the relationship between serum concentrations of voriconazole and posaconazole and their efficacy or toxicities was evaluated. This information was then integrated to formulate recommendations for use of therapeutic drug monitoring in clinical settings.

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

“…The triazoles are the main agents where TDM is considered helpful in optimising treatment. [111][112][113] Although levels of fluconazole can vary significantly between patients, the variability is largely due to renal function, and hence doses are best adjusted according to creatinine clearance. 114 There is increasing evidence to support TDM in routine use of itraconazole, voriconazole and posaconazole.…”

Plasma Voriconazole Estimation by HPLC

“…Steady-state plasma concentrations are attained after 5-7 days of treatment. Comprising a narrow therapeutic index, pharmacokinetics of Vrc is profoundly influenced by food and drug interactions and inter-individual variability regardless of route of administration [8][9][10][11]. Factors well documented to be associated with interindividual variability of voriconazole exposure include liver dysfunction, gastrointestinal abnormalities (e.g.…”

“…Factors well documented to be associated with interindividual variability of voriconazole exposure include liver dysfunction, gastrointestinal abnormalities (e.g. mucositis or diarrhea) impairing drug absorption, intake with or without food, alcohol abuse in the past, concomitant use of potent CYP450 inducers or inhibitors, CYP2C19 genetic polymorphism; thus rationalizing the necessity for therapeutic drug monitoring (TDM) of voriconazole [6][7][8][9][10][11][12][13].…”

“…Quantification of azoles by various analytical techniques such as high performance liquid chromatography (HPLC) [5,9,14], liquid chromatography-tandem mass spectrometry methods (LC-MS) [15] and microbiological methods [16] have been reported. HPLC methods are specific and sensitive for plasma voriconazole concentrations however, special columns and sample preparation with liquid phase extraction and/or tedious precipitation steps are involved [5,17].…”

Farmacocinética de posaconazol en la profilaxis y tratamiento de la infección fúngica invasora en niños inmunocomprometidos en un hospital pediátrico

“…Aunque las concentraciones objetivo de PSC no se han establecido definitivamente, varios estudios han demostrado la relación entre la respuesta clínica y la CP de este antifúngico [12][13][14] . En un estudio de investigación abierto, Walsh y cols.…”