Mortality and morbidity due to invasive fungal infections have increased over the years. Posaconazole is a second-generation triazole agent with an extended spectrum of activity, which shows a high interindividual variability in its plasma levels, rendering dosing in many patients inconsistent or inadequate. Hence, posaconazole therapeutic drug monitoring, which is easily available in clinical practice, may improve treatment success and safety. The aim of the study was to describe posaconazole pharmacokinetics, and to evaluate the utility of therapeutic drug monitoring for therapy and prophylaxis in a cohort of adult patients. A fully validated chromatographic method was used to quantify posaconazole concentration in plasma collected from adult patients at the end of the dosing interval. Associations between variables were tested using the Pearson test. The Mann-Whitney test was used to probe the influence of categorical variables on continuous ones. A high inter-individual variability was shown. Of the 172 enrolled patients, among those receiving the drug by the oral route (N = 170), gender significantly influenced drug exposure: males showed greater posaconazole concentration than females (p = 0.028). This study highlights the importance of therapeutic drug monitoring in those with invasive fungal infections and its significant clinical implications; moreover we propose, for the first time, the possible influence of gender on posaconazole exposure.

Evaluation of Posaconazole Pharmacokinetics in Adult Patients with Invasive Fungal Infection

Allegra, Sarah
First
;
Fatiguso, Giovanna;De Francia, Silvia;Favata, Fabio;Pirro, Elisa;Carcieri, Chiara;De Nicolò, Amedeo;Cusato, Jessica;Di Perri, Giovanni;D'avolio, Antonio
Last
2017-01-01

Abstract

Mortality and morbidity due to invasive fungal infections have increased over the years. Posaconazole is a second-generation triazole agent with an extended spectrum of activity, which shows a high interindividual variability in its plasma levels, rendering dosing in many patients inconsistent or inadequate. Hence, posaconazole therapeutic drug monitoring, which is easily available in clinical practice, may improve treatment success and safety. The aim of the study was to describe posaconazole pharmacokinetics, and to evaluate the utility of therapeutic drug monitoring for therapy and prophylaxis in a cohort of adult patients. A fully validated chromatographic method was used to quantify posaconazole concentration in plasma collected from adult patients at the end of the dosing interval. Associations between variables were tested using the Pearson test. The Mann-Whitney test was used to probe the influence of categorical variables on continuous ones. A high inter-individual variability was shown. Of the 172 enrolled patients, among those receiving the drug by the oral route (N = 170), gender significantly influenced drug exposure: males showed greater posaconazole concentration than females (p = 0.028). This study highlights the importance of therapeutic drug monitoring in those with invasive fungal infections and its significant clinical implications; moreover we propose, for the first time, the possible influence of gender on posaconazole exposure.
2017
5
4
66
73
HPLC; antifungal; invasive fungal infections (IFIs); therapeutic drug monitoring (TDM); triazoles
Allegra, Sarah; Fatiguso, Giovanna; De Francia, Silvia; Favata, Fabio; Pirro, Elisa; Carcieri, Chiara; De Nicolò, Amedeo; Cusato, Jessica; Di Perri, G...espandi
File in questo prodotto:
File Dimensione Formato  
biomedicines-05-00066.pdf

Accesso aperto

Tipo di file: PDF EDITORIALE
Dimensione 378.2 kB
Formato Adobe PDF
378.2 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1652652
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 12
social impact