Muraki Yuichi, Iwamoto Takuya, Kagawa Yoshiyuki, Sakurai Hiroyuki, Usui Masanobu, Isaji Shuji, Uemoto Shinji, Okuda Masahiro
Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University, Japan.
Biol Pharm Bull. 2009 Apr;32(4):750-4. doi: 10.1248/bpb.32.750.
The objective of this study was to propose a clinically effective and safe micafungin (MCFG) treatment for 20 recipients of living-donor liver transplantations (LDLTs), after considering the influence of liver function on its plasma pharmacokinetics. In all patients, an improvement of clinical symptoms was observed after MCFG treatment. Liver and renal functions were not significantly changed by the administration of MCFG. In the recipients, the trough plasma concentration of MCFG was 4.6+/-2.1 [corrected] microg/ml (mean+/-S.D.), which was dependent on the dose (p=0.0033). Additionally, there was a good correlation between the trough and peak MCFG plasma concentrations (p<0.0001). The trough concentration of MCFG was significantly correlated with serum total bilirubin levels (p=0.0166). In addition, the MCFG concentration/dose (C/D) ratio was significantly higher in the patients with total bilirubin levels >5 mg/dl than in those with total bilirubin levels < or =5 mg/dl (p<0.0001). The C/D ratio of MCFG was weakly but not significantly correlated with total bilirubin levels at total bilirubin levels >5 mg/dl (p=0.0508). Therefore, a reduced dose of MCFG should be considered when total bilirubin levels are >5 mg/dl. Furthermore, careful monitoring of total bilirubin levels is recommended during MCFG treatment in LDLT-recipients with severe liver dysfunction. These results provide helpful advice about MCFG administration for the treatment of fungal infections in LDLT patients with fluctuating liver function.
本研究的目的是在考虑肝功能对米卡芬净（MCFG）血浆药代动力学影响的情况下，为20例活体肝移植（LDLT）受者提出一种临床有效且安全的MCFG治疗方案。在所有患者中，MCFG治疗后临床症状均有改善。给予MCFG后，肝肾功能无明显变化。在受者中，MCFG的谷浓度为4.6±2.1[校正后]μg/ml（平均值±标准差），这取决于剂量（p=0.0033）。此外，MCFG血浆谷浓度与峰浓度之间存在良好的相关性（p<0.0001）。MCFG的谷浓度与血清总胆红素水平显著相关（p=0.0166）。此外，总胆红素水平>5mg/dl的患者中MCFG浓度/剂量（C/D）比显著高于总胆红素水平≤5mg/dl的患者（p<0.0001）。在总胆红素水平>5mg/dl时，MCFG的C/D比与总胆红素水平呈弱相关但无显著相关性（p=0.0508）。因此，当总胆红素水平>5mg/dl时，应考虑降低MCFG的剂量。此外，对于肝功能严重受损的LDLT受者，建议在MCFG治疗期间密切监测总胆红素水平。这些结果为MCFG在肝功能波动的LDLT患者中治疗真菌感染的给药提供了有益的建议。
