Comparison of the probability of target attainment of anidulafungin against Candida spp. in patients with acute leukaemia

Abstract

This study aimed to investigate the probability of target attainment (PTA) of various anidulafungin dosing regimens against Candida spp. in patients with acute leukaemia. A Monte Carlo simulation was performed using a previously published population pharmacokinetic model. The following dosing scenarios were evaluated: 200mg loading dose (LD) on Day 1 then 100mg daily (manufacturer's recommended dosing regimen); 200mg LD on Day 1 then 100mg every 48h (q48h); and 200mg q48h, 200mg every 72h (q72h) and 300mg q72h. For each dosing regimen, free drug concentrations were calculated to evaluate the effect of 99% protein binding. The PTA at various pharmacodynamic (PD) targets was determined as the percentage of subjects who achieved a free drug area under the plasma concentration–time curve over the minimum inhibitory concentration ratio (ƒAUC/MIC) or a free drug maximum plasma concentration over the minimum inhibitory concentration ratio (ƒCmax/MIC) above the PD targets. PTA expectation values were then calculated for each dosing regimen. The currently recommended dosing regimen of anidulafungin was not optimal for invasive candidiasis in patients with acute leukaemia. Alternate dosing strategies with higher doses and extended dosing intervals (intermittent dosing) achieved better target attainment. This is the first study to optimise therapy with anidulafungin using Monte Carlo simulation. These results provide a rationale in support of future clinical investigation of intermittent dosing of anidulafungin.