Effective Blood Concentration of Micafungin for Pulmonary Aspergillosis

Abstract

We previously reported that a 150 mg or higher daily dose is necessary for treatment of pulmonary aspergillosis with micafungin (MCFG) alone in patients with blood diseases. Since a delay in the treatment of pulmonary aspergillosis has a major influence on patient survival, clarification of the effective blood concentration of MCFG enables rapid treatment. Establishment of an appropriate dose is also useful for reducing the risk of adverse effects, such as MCFG-induced impairment of liver function. Aiming for the rapid and safe treatment of pulmonary aspergillosis, we established new clinical diagnostic criteria of mycosis and MCFG therapeutic effect judgment criteria, and investigated the effective blood concentration of MCFG for mycosis. The blood trough level of MCFG in patients with blood diseases at each clinical improvement rating of pulmonary aspergillosis was 5.23؎2.44 m mg/ml in markedly improved cases, 4.08؎2.63 m mg/ml in improved cases, and 3.45؎1.63 m mg/ml in successfully prevented cases, showing no significant difference among the 3 groups. Based on this finding, it is advisable to target a 5 m mg/ml or higher blood trough level of MCFG in establishing the dose for aspergillosis in patients with blood diseases.

The Impact of Total Bilirubin on Plasma Micafungin Levels in Living-Donor Liver Transplantation Recipients with Severe Liver Dysfunction

“…Therefore, preventive or preemptive treatments against fungal infections are needed for LDLT-recipients. 14) Several reports have demonstrated that MCFG is a safe and effective antifungal agent, 9,[15][16][17] suggesting that dose adjustment is not required for elderly patients or patients with moderate liver dysfunction or severe kidney dysfunction. 9,12) However, information on the efficacy and safety of MCFG for the treatment of fungal infections in LDLT-recipients has been limited due to the small sample sizes of the studies reported previously [18][19][20] ; i.e., less than 9 LDLT-recipients in each study.…”

“…15) On the other hand, Kishino et al demonstrated that a therapeutic drug level can be achieved by prophylactic administration of MCFG at a dose of 40-50 mg/d.…”

Direct-injection HPLC method of measuring micafungin in human plasma using a novel hydrophobic/hydrophilic hybrid ODS column

“…In a clinical study in Japan, the C max values of MCFG were 14.30 g/mL (single administration of 150 mg) and 2.52 g/mL (single administration of 25 mg) [19]. Shimoeda et al recommended 5.0 g/mL or higher as a target blood trough level of MCFG in establishing a dose for treating aspergillosis in patients with blood diseases [20]. The sensitivity of our method was considered satisfactory for clinical application.…”

Pharmacokinetics of micafungin in patients undergoing allogeneic hematopoietic stem cell transplantation

“…However, Shimoeda et al. compared the MCFG Cmin in patients grouped according to the response of pulmonary aspergillosis based on their original criteria. The mean MCFG Cmin level was higher in patients with “marked improvement” compared to those with “improvement” (5.23 μg/mL vs. 4.08 μg/mL), although the difference was not statistically significant.…”