Voriconazole plasma exposure greatly varies among haematological patients. The purpose of this study was to identify the magnitude of influence of comedications with CYP inhibitors and/or with CYP inhibitors plus CYP inducers on voriconazole trough level (Cmin). Voriconazole Cmin was retrospectively assessed among haematological patients who underwent therapeutic drug monitoring (TDM). Univariate and multivariate linear mixed-effect regression analyses were performed to identify the independent predictors of normalized Cmin. Of the 83 included patients, 35 had comedications with CYP inhibitors (omeprazole or pantoprazole) and 21 with CYP inhibitors (omeprazole or pantoprazole) plus CYP inducers (methylprednisolone, dexamethasone, phenobarbital, rifampin or carbamazepine). Median Cmin value (n = 199) was 2.4 mg/L with a wide range of distribution (<0.2-13.5 mg/L). Median (IQR) normalized voriconazole Cmin value was significantly higher in the presence of CYP inhibitors (4.20 mg/L, 3.23-5.51 mg/L) than either in the absence of interacting cotreatments (2.55 mg/L, 1.54-3.47 mg/L) or in the presence of CYP inhibitors plus CYP inducers (2.16 mg/L, 1.19-3.09 mg/L). The presence of CYP inhibitors was highly significantly associated with Cmin >5.5 mg/L (OR: 23.22, 95% CI: 3.01-179.09, p = 0.003). No significant association emerged when CYP inhibitors were coadministered with CYP inducers (OR: 3.53, 95% CI: 0.36-34.95, p = 0.280). The amount of expected Cmin increase was significantly influenced by both the type and the dose of the administered proton pump inhibitor. The study highlights that the benefit from TDM of voriconazole may be maximal in those patients who are cotreated with CYP inhibitors and/or with CYP inhibitors plus CYP inducers, especially when receiving proton pump inhibitors (PPIs) at very high dosages intravenously.
Attenzione! Scheda prodotto non ancora validata dall'Ateneo
Dati e metadati della pubblicazione sono in fase di verifica da parte dell'Ateneo. In caso di errori o violazione dei diritti d'autore, contattare: email@example.com
|Data di pubblicazione:||2016|
|Titolo:||Variability of Voriconazole Trough Levels in Haematological Patients: Influence of Comedications with cytochrome P450(CYP) Inhibitors and/or with CYP Inhibitors plus CYP Inducers|
|Autori:||Cojutti, Piergiorgio; Candoni, Anna; Forghieri, Fabio; Isola, Miriam; Zannier, Maria Elena; Bigliardi, Sara; Luppi, Mario; Fanin, Renato; Pea, Federico|
|Digital Object Identifier (DOI):||10.1111/bcpt.12530|
|Appare nelle tipologie:||Articolo su rivista|
File in questo prodotto:
I documenti presenti in Iris Unimore sono rilasciati con licenza Creative Commons Attribuzione - Non commerciale - Non opere derivate 3.0 Italia, salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris