Monitoring plasma voriconazole levels following intravenous administration in critically ill patients: an observational study

Abstract 

Data relating to the pharmacokinetics of voriconazole in critically ill patients are lacking. A prospective observational study was conducted on 18 non-consecutive critically ill patients aged 24–97 years, comprising 12 patients with normal renal function (NRF) [creatinine clearance (CL_Cr) ≥60mL/min] and 6 patients with moderate renal impairment (MRI) (CL_Cr 40–55mL/min), administered voriconazole intravenously (6mg/kg loading dose and 3–4mg/kg twice daily thereafter) in order to determine the suitability of these doses in this patient population. Steady-state blood levels were monitored and liver and renal function were recorded throughout treatment. Large variability in patient plasma levels was observed, ranging from 37% at ≤1mg/L (minimum inhibitory concentration at which, for most fungal pathogens, 90% of isolates are susceptible) to 19% at >5.5mg/L. Moreover, maintaining trough concentrations above clinical breakpoints was not consistently achieved because 16/30 (53%) were ≤1mg/L. In a few MRI patients, average concentrations were found to be significantly different compared with those of NRF patients administered the same dose, however this difference was not noted in pharmacokinetic parameters following dose normalisation. None of the patients experienced deterioration in renal or liver function. Recommended voriconazole doses are inadequate to achieve drug concentrations >1μg/mL over the entire dosing interval in some critically ill patients.

Keywords: Voriconazole, Critically ill patients, Normal to moderate renal impairment, Plasma concentration monitoring, Pharmacokinetics