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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Phase II dose escalation study of caspofungin for invasive Aspergillosis.
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Phase II dose escalation study of caspofungin for invasive Aspergillosis.

机译：卡泊芬净治疗侵袭性曲霉病的II期剂量递增研究。

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Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA). The safety and pharmacokinetics of escalating dosages of caspofungin were investigated in IA. Eight patients each received caspofungin 70, 100, 150, or 200 mg once a day (QD). Dose-limiting toxicity (DLT) was defined as the same non-hematological treatment-related adverse event of grade >/= 4 in 2 of 8 patients or >/= 3 in 4 of 8 patients in a cohort. A total of 46 patients (median age, 61 years; 21 female; 89% with hematological malignancies) received caspofungin (9, 8, 9, and 20 patients in the 70-, 100-, 150-, and 200-mg cohorts) for a median of 24.5 days. Plasma pharmacokinetics were linear across the investigated dosages and followed a two-compartment model, with weight as the covariate on clearance and sex as the covariate on central volume of distribution. Simulated peak plasma concentrations at steady state ranged from 14.2 to 40.6 mg/liter (28%), trough concentrations from 4.1 to 11.8 mg/liter (58%), and area under the concentration-time curve from 175 to 500 mg/liter/h (32%) (geometric mean, geometric coefficient of variation). Treatment was well tolerated without dose-limiting toxicity. The rate of complete or partial responses was 54.3%, and the overall mortality at 12-week follow-up was 28.3%. In first-line treatment of invasive aspergillosis, daily doses of up to 200 mg caspofungin were well tolerated and the maximum tolerated dose was not reached. Pharmacokinetics was linear. Response rates were similar to those previously reported for voriconazole and liposomal amphotericin.
机译：我们的目标是评估卡泊芬净治疗侵袭性曲霉病（IA）的最大耐受剂量。在IA中研究了卡泊芬净剂量递增的安全性和药代动力学。八名患者各自每天接受一次卡泊芬净70、100、150或200 mg（QD）。限剂量毒性（DLT）被定义为同一非血液学治疗相关不良事件，队列中8名患者中有2名> / = 4，或8名患者中4名中有> / = 3。共有46例患者（中位年龄为61岁; 21例女性; 89％的血液系统恶性肿瘤）接受卡泊芬净（70、100、150和200 mg队列中的9、8、9和20例患者）平均为24.5天。血浆药代动力学在所研究的剂量范围内是线性的，并遵循两室模型，体重为清除率的协变量，性别为分布中心体积的协变量。稳态时的模拟峰值血浆浓度范围为14.2至40.6 mg / l（28％），波谷浓度范围为4.1至11.8 mg / l（58％），浓度-时间曲线下的面积为175至500 mg / l / L h（32％）（几何平均值，几何变异系数）。治疗耐受性好，无剂量限制性毒性。完全或部分缓解的发生率为54.3％，随访12周的总死亡率为28.3％。在侵袭性曲霉病的一线治疗中，每日剂量最高200 mg卡泊芬净的耐受性良好，未达到最大耐受剂量。药代动力学是线性的。反应率与以前报道的伏立康唑和脂质体两性霉素相似。

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