Abstract：
Methicillin-resistant Staphylococcus aureus infections are increasing in prevalence in patients with cystic fibrosis (CF) and are associated with worsening lung function and increased mortality. Lefamulin is a pleuromutilin antimicrobial approved to treat community-acquired bacterial pneumonia based on potent in vitro activity and clinical efficacy. This Phase I, open-label, randomized crossover study assessed the safety and pharmacokinetic profile of oral and intravenous (IV) lefamulin in adults with CF.
The study comprised 2 dosing periods in which adults with CF (N = 13) received a single dose of lefamulin via a 150-mg IV infusion or 600-mg immediate-release orally administered tablet, separated by a 4- to 7-day washout period. Pharmacokinetic and safety parameters were assessed after lefamulin treatment.
Single doses of lefamulin administered via oral tablet or IV infusion resulted in comparable drug exposure, and sputum analysis suggested rapid penetration of lefamulin into the lung. Comparison of the present results with those obtained from prior single-dose studies of healthy volunteers indicate no meaningful difference in the pharmacokinetic properties of lefamulin in patients with CF. Treatment-emergent adverse events were consistent with previous reports, and the majority were mild in severity.
These results show similar lefamulin pharmacokinetic and safety profiles between patients with CF and healthy volunteers receiving the same oral and IV doses, suggesting no need for lefamulin dose adjustment in patients with CF and indicating the potential of lefamulin as therapy for lung infections in patients with CF.
gov identifier: NCT05225805.
The study comprised 2 dosing periods in which adults with CF (N = 13) received a single dose of lefamulin via a 150-mg IV infusion or 600-mg immediate-release orally administered tablet, separated by a 4- to 7-day washout period. Pharmacokinetic and safety parameters were assessed after lefamulin treatment.
Single doses of lefamulin administered via oral tablet or IV infusion resulted in comparable drug exposure, and sputum analysis suggested rapid penetration of lefamulin into the lung. Comparison of the present results with those obtained from prior single-dose studies of healthy volunteers indicate no meaningful difference in the pharmacokinetic properties of lefamulin in patients with CF. Treatment-emergent adverse events were consistent with previous reports, and the majority were mild in severity.
These results show similar lefamulin pharmacokinetic and safety profiles between patients with CF and healthy volunteers receiving the same oral and IV doses, suggesting no need for lefamulin dose adjustment in patients with CF and indicating the potential of lefamulin as therapy for lung infections in patients with CF.
gov identifier: NCT05225805.
摘要：
目的：囊性纤维化（CF）患者耐甲氧西林金黄色葡萄球菌感染的患病率正在增加，并与肺功能恶化和死亡率增加有关。Lefamulin是一种基于有效的体外活性和临床疗效而被批准用于治疗社区获得性细菌性肺炎的截短胸膜素抗微生物剂。第一阶段,开放标签，随机交叉研究评估了成人CF患者口服和静脉（IV）lefamulin的安全性和药代动力学特征。
方法：该研究包括2个给药期，其中患有CF的成年人（N=13）通过150mg静脉输注或600mg口服速释片剂接受单剂量的lefamulin，由4至7天的冲洗期分开。在lefamulin治疗后评估药代动力学和安全性参数。
结果：通过口服片剂或静脉输注单剂量利福莫林导致相当的药物暴露，痰液分析提示lefamulin快速渗入肺部。将当前结果与先前对健康志愿者进行的单剂量研究获得的结果进行比较表明，在CF患者中，lefamulin的药代动力学特性没有有意义的差异。治疗引起的不良事件与以前的报告一致，大多数人严重程度较轻。
结论：这些结果显示，CF患者与接受相同口服和静脉给药的健康志愿者之间的利福蛋白药代动力学和安全性相似，提示CF患者不需要调整lefamulin剂量，并表明lefamulin可能作为CF患者肺部感染的治疗方法。
结果：gov标识符：NCT05225805。
方法：该研究包括2个给药期，其中患有CF的成年人（N=13）通过150mg静脉输注或600mg口服速释片剂接受单剂量的lefamulin，由4至7天的冲洗期分开。在lefamulin治疗后评估药代动力学和安全性参数。
结果：通过口服片剂或静脉输注单剂量利福莫林导致相当的药物暴露，痰液分析提示lefamulin快速渗入肺部。将当前结果与先前对健康志愿者进行的单剂量研究获得的结果进行比较表明，在CF患者中，lefamulin的药代动力学特性没有有意义的差异。治疗引起的不良事件与以前的报告一致，大多数人严重程度较轻。
结论：这些结果显示，CF患者与接受相同口服和静脉给药的健康志愿者之间的利福蛋白药代动力学和安全性相似，提示CF患者不需要调整lefamulin剂量，并表明lefamulin可能作为CF患者肺部感染的治疗方法。
结果：gov标识符：NCT05225805。
