In vitro and in vivo exposure-effect relationship of liposomal amphotericin B against Aspergillus fumigatus

ABSTRACT

In vitro pharmacokinetic/pharmacodynamic data of liposomal amphotericin B (L-AMB) were compared with animal data from neutropenic and non-neutropenic models of azole-susceptible and azole-resistant invasive aspergillosis. L-AMB was equally effective. The in vitro fC_max/MIC ratio associated with 50% of maximal activity was 0.31 (0.29-0.33) similar to neutropenic but not to non-neutropenic mice [0.11 (0.06-0.20)]. Simulation analysis indicated that standard L-AMB doses (1-3mg/kg) are adequate for non-neutropenic patients but higher doses (7.5-10mg/kg) may be required for neutropenic patients for most A. fumigatus isolates (MIC≤1mg/L).