The action mechanism of a new candin antifungal agent, micafungin (MCFG), which was developed as the sixth antifungal agent in Japan, differs from that of conventional antifungal agents, and this agent may be clinically useful. MCFG has a broad spectrum against Candida and Aspergillus in vitro by inhibiting the biosynthesis of the main constituent comprising the fungal cellular wall, 1,3-b-D glucan.1,2) As this agent shows favorable lung transfer, 3) it may be useful for preventing and treating pulmonary mycosis.We previously reported the efficacy of this agent and the incidence of side effects in 17 patients with hematological diseases to whom MCFG was administered to treat/prevent pulmonary aspergillosis. 4) Our study suggested that 150 mg or more of MCFG is required to treat/prevent pulmonary aspergillosis; however, the necessity of adjusting the dose in patients with liver/kidney hypofunction and the presence or absence of interactions with other agents remain to be clarified. As an immunosuppressive agent, tacrolimus , is administered to patients after hematopoietic stem cells transplantation from non-relatives for a long period, it should be confirmed whether interactions related to combination therapy with MCFG appear.In this study, we measured the blood level of MCFG in 29 patients with hematological diseases, and analyzed the data. We report findings regarding administration to patients with liver/kidney hypofunction and combination therapy with FK-506.
MATERIALS AND METHODS
SubjectsThe subjects were 29 patients who were admitted to the First Department of Internal Medicine (Department of Hematology) in Nagano Red Cross Hospital between February 2003 and October 2004. Written informed consent regarding the measurement of the blood MCFG level was obtained from the patients or their families. As a rule, blood was collected 3 d or more after the start of administration, when MCFG reached a steady state, to obtain a trough value. If necessary, blood was collected in accordance with the general condition.Informed Consent In obtaining informed consent from the patients or their families, we paid attention to protect the patients' rights according to the Helsinki declaration. In addition, it was explained that blood samples were not used for purposes other than this study. The Ethics Committee in our hospital approved this study.Preparation of the Solutions A standard solution of MCFG and a solution containing an internal standard substance (IS), FR195743, were supplied by Fujisawa Pharmaceutical Co., Ltd. MCFG was dissolved in ethanol at a concentration of 100 mg/ml, and the standard stock solution thus prepared was stored at Ϫ20°C. The IS was dissolved in 0.02 mol/l potassium dihydogenphosphate/acetonitrile (50/50, v/v) at a concentration of 100 mg/ml, and the IS stock solution thus prepared was stored at 4°C. The standard stock solution was diluted with ethanol to make standard working solutions at a concentration of 25, 10, 2.5, 1, 0.25, and 0.05 mg/ml, respectively. The IS stock solution was diluted with ...