Xie Rujia, McFadyen Lynn, Raber Susan, Swanson Robert, Tawadrous Margaret, Leister-Tebbe Heidi, Cohen-Wolkowiez Michael, Benjamin Daniel K, Liu Ping
Pharmacometrics, Pfizer Asia Manufacturing Pte Ltd, Singapore City, Singapore.
Pharmacometrics, Pfizer Research and Development UK Ltd, Kent, UK.
Clin Pharmacol Ther. 2020 Aug;108(2):316-325. doi: 10.1002/cpt.1831. Epub 2020 Apr 19.
In a pooled population analysis, we investigated the pharmacokinetics of i.v. anidulafungin in four studies across a full range of adult and pediatric ages in patients with confirmed, suspected, or at high risk of invasive candidiasis (IC). Relationships between anidulafungin exposure and key efficacy end points (global response of success and all-cause mortality) and safety end points (all-cause hepatic or gastrointestinal adverse events) in all patients and separately in pediatric patients and the appropriate dosing regimen for IC treatment in pediatric patients were evaluated. Pediatric patients received a 3.0 mg/kg (maximum 200 mg) i.v. loading dose and 1.5 mg/kg (maximum 100 mg) daily thereafter. Adults received a 200 mg i.v. loading dose and 100 mg daily thereafter. Estimated systemic anidulafungin exposures were similar across age groups (neonates to adults) at the weight-based doses studied in pediatric patients. No clear associations were identified between anidulafungin exposure and efficacy or safety end points.
在一项汇总人群分析中，我们在四项研究中调查了静脉注射阿尼芬净在确诊、疑似或有侵袭性念珠菌病（IC）高风险的全年龄段成人和儿科患者中的药代动力学。评估了阿尼芬净暴露量与所有患者以及儿科患者单独的关键疗效终点（成功的总体反应和全因死亡率）和安全性终点（全因肝脏或胃肠道不良事件）之间的关系，以及儿科患者IC治疗的合适给药方案。儿科患者静脉注射负荷剂量为3.0mg/kg（最大200mg），此后每日1.5mg/kg（最大100mg）。成人静脉注射负荷剂量为200mg，此后每日100mg。在所研究的儿科患者基于体重的剂量下，各年龄组（从新生儿到成人）的阿尼芬净全身暴露量估计相似。未发现阿尼芬净暴露量与疗效或安全性终点之间存在明确关联。
