Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Ther Drug Monit. 2022 Oct 1;44(5):641-650. doi: 10.1097/FTD.0000000000000980.
Limited evidence concerning optimal azole dosing regimens currently exists for antifungal prophylaxis in hemato-oncological pediatric patients.
Hemato-oncological children receiving intravenous or oral isavuconazole or voriconazole for primary antifungal prophylaxis at IRCCS Azienda Ospedaliero-Universitaria of Bologna during November 2020 to October 2021 and undergoing CPA programs based on real-time therapeutic drug monitoring (TDM) were retrospectively analyzed. CPAs for isavuconazole and voriconazole and the number of dosage adjustments were collected. Normalized trough concentrations [(C min )/dose/kg] were calculated for both drugs at each TDM assessment, and the coefficient of variation was determined. The efficacy and safety of the drugs were evaluated.
Sixteen hemato-oncological pediatric patients received azole prophylaxis (mean age and weight: 9.1 ± 4.9 years and 32.6 ± 16.0 kg; 6 isavuconazole and 10 voriconazole). Sixty and 89 CPAs were delivered as isavuconazole and voriconazole, respectively. Dosage adjustments were needed in 3.3% of cases for isavuconazole and 53.9% of cases for voriconazole ( P < 0.001). At first TDM, achievement of the desired target during standard dosing regimens was higher for isavuconazole (83.3%) than for voriconazole (10.0%; P = 0.008). Dispersion of normalized concentrations was higher for voriconazole (CV = 139.1% vs. CV = 79.4%). Elevation of ALT and aspartate aminotransferase levels between baseline and the third month was higher in patients receiving voriconazole (median, 28 vs. 90 U/L; P = 0.038, and 19 vs. 65.5 U/L; P = 0.002).
Our findings suggest that there is limited variability in isavuconazole exposure in hemato-oncological pediatric patients receiving azole prophylaxis , resulting in a low need for CPA-guided dosage adjustments.
目前针对血液肿瘤儿科患者抗真菌预防治疗的唑类药物最佳剂量方案的证据有限。
回顾性分析 2020 年 11 月至 2021 年 10 月期间在意大利博洛尼亚 IRCCS Azienda Ospedaliero-Universitaria 接受静脉或口服伊曲康唑或伏立康唑进行原发性抗真菌预防治疗且正在进行基于实时治疗药物监测（TDM）的临床药师方案（CPA）的血液肿瘤儿科患者。收集伊曲康唑和伏立康唑的 CPA 数量和剂量调整数量。在每次 TDM 评估时计算两种药物的标准化谷浓度[（C min ）/剂量/体重]，并确定变异系数。评估药物的疗效和安全性。
16 名血液肿瘤儿科患者接受唑类药物预防治疗（平均年龄和体重：9.1 ± 4.9 岁和 32.6 ± 16.0 公斤；6 例伊曲康唑和 10 例伏立康唑）。分别为伊曲康唑和伏立康唑提供了 60 和 89 次 CPA。伊曲康唑需要调整剂量的病例占 3.3%，伏立康唑需要调整剂量的病例占 53.9%（P < 0.001）。首次 TDM 时，标准剂量方案下伊曲康唑（83.3%）达到目标的比例高于伏立康唑（10.0%；P = 0.008）。伏立康唑的标准化浓度分散性更高（CV = 139.1%比 CV = 79.4%）。伏立康唑组患者 ALT 和天冬氨酸氨基转移酶水平从基线到第三个月升高（中位数分别为 28 和 90 U/L；P = 0.038，和 19 和 65.5 U/L；P = 0.002）。
我们的研究结果表明，接受唑类药物预防治疗的血液肿瘤儿科患者伊曲康唑暴露的变异性有限，因此需要 CPAs 指导的剂量调整的可能性较低。
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