골수 이식 환자에서 Azole계 항진균제와의 병용으로 인한 Cyclosporine의 혈중농도 변화
Changes in blood concentrations of cyclosporine after combination with azoles in bone marrow transplant recipients
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Many studies of azole antifungal agents report that itraconazole is a more potent inhibitor of cytochrome P450 3A4(CYP3A4) than fluconazole. However, only a few reports from various clinical studies support it. This study was performed to study the effect of itraconazole and fluconazole on metabolism of cyclosporine(CsA), substrate of CYP3A4, by analyzing the blood concentrations of CsA. Total 141 patients who underwent bone marrow transplantation and were administered itraconazole or fluconazole combined with CsA from January 2008 to June 2009 in Asan Medical Center were enrolled. Data was collected retrospectively from electronic medical record(EMR). 56 patients received 389.29mg/day itraconazole(Sporanox solution, Janssen Korea) and 85 patients received 128.24mg/day fluconazole(Diflucan cpasule, Pfizer Korea). The dosage of CsA was not significantly different between itraconazole group(intravenous CsA 2.95±0.21mg/kg/day; oral CsA 3.59±1.51mg/kg/day) and fluconazole group(2.90±0.33mg/kg/day, p=0.351; 3.88±1.54mg/kg/day, p=0.466). Also, the period of combination was about 19 days in both groups. The blood concentrations of CsA were analyzed after combination with azoles. Data was collected three times; the first level(pre-steady-state level), the third level(steady-state level) and the highest level(peak TDM level) during the period of combination. In itraconazole group, blood concentrations of CsA were 101.60±59.91, 195.88±68.03 and 339.63±143.75ng/ml, respectively and peak TDM level was higher than the therapeutic range of CsA(100~300ng/ml). In fluconazole group, blood concentrations of CsA were 96.85±45.80(p=0.615), 173.74±60.75 (p=0.051) and 272.35±128.88ng/ml(p=0.006), respectively and peak TDM level was significantly lower than in itraconazole group. In conclusion, more careful monitoring of blood concentrations of CsA is recommended when CsA is combined with itraconazole than when combined with fluconazole.
Abstract
Many studies of azole antifungal agents report that itraconazole is a more potent inhibitor of cytochrome P450 3A4(CYP3A4) than fluconazole. However, only a few reports from various clinical studies support it. This study was performed to study the effect of itraconazole and fluconazole on metabolism of cyclosporine(CsA), substrate of CYP3A4, by analyzing the blood concentrations of CsA. Total 141 patients who underwent bone marrow transplantation and were administered itraconazole or fluconazole combined with CsA from January 2008 to June 2009 in Asan Medical Center were enrolled. Data was collected retrospectively from electronic medical record(EMR). 56 patients received 389.29mg/day itraconazole(Sporanox solution, Janssen Korea) and 85 patients received 128.24mg/day fluconazole(Diflucan cpasule, Pfizer Korea). The dosage of CsA was not significantly different between itraconazole group(intravenous CsA 2.95±0.21mg/kg/day; oral CsA 3.59±1.51mg/kg/day) and fluconazole group(2.90±0.33mg/kg/day, p=0.351; 3.88±1.54mg/kg/day, p=0.466). Also, the period of combination was about 19 days in both groups. The blood concentrations of CsA were analyzed after combination with azoles. Data was collected three times; the first level(pre-steady-state level), the third level(steady-state level) and the highest level(peak TDM level) during the period of combination. In itraconazole group, blood concentrations of CsA were 101.60±59.91, 195.88±68.03 and 339.63±143.75ng/ml, respectively and peak TDM level was higher than the therapeutic range of CsA(100~300ng/ml). In fluconazole group, blood concentrations of CsA were 96.85±45.80(p=0.615), 173.74±60.75 (p=0.051) and 272.35±128.88ng/ml(p=0.006), respectively and peak TDM level was significantly lower than in itraconazole group. In conclusion, more careful monitoring of blood concentrations of CsA is recommended when CsA is combined with itraconazole than when combined with fluconazole.
참고문헌 (13)
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