Pharmacokinetic-pharmacodynamic modeling of dalbavancin, a novel glycopeptide antibiotic
Pharmacokinetic-pharmacodynamic modeling of dalbavancin, a novel glycopeptide antibiotic
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DOI：
10.1177/0091270008321273
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发表时间：
2008-09-01
影响因子：
2.9
通讯作者：
Damle, Bharat
中科院分区：
文献类型：
--
作者：
Dowell, James A.;Goldstein, Beth R.;Damle, Bharat
达巴万星是一种新型糖肽，每周一次，每次2剂，正在开发用于治疗革兰氏阳性菌引起的复杂皮肤和皮肤结构感染。使用群体药代动力学数据和临床试验分离株的最小药代动力学浓度（MIG）对达巴霉素进行蒙特卡罗模拟。时间依赖性目标是维持游离药物浓度高于MIC 14天（t > ABC）。浓度依赖性目标是浓度-时间曲线下面积（AUC）/MIC比值，金黄色葡萄球菌约为1000，链球菌约为100。这些目标用于估计达巴霉素的敏感性折点。对于金黄色葡萄球菌，估计的敏感性断点为
Dalbavancin is a novel glycopeptide with a 2-dose, once--weekly dosing regimen that is being developed for the treatment of complicated skin and skin structure infections caused by gram-positive bacteria. Monte Carlo simulations were performed for dalbavancin using population pharmacokinetic data and minimum inhibitoiy concentrations (MIGs) for clinical trial isolates. The time-dependent target was the maintenance of free drug concentrations above the MIC for 14 days (t > ABC). The concentration-dependent target was an area under the concentration-time curve (AUG)/MIC ratio of approximately 1000 for Staphylococcus aureus and 100 for Streptococcus sp. These targets were used to estimate susceptibility breakpoints for dalbavancin. For S aureus, the estimated susceptibility breakpoint was