Clinical Pharmacokinetics and Pharmacodynamics of Telavancin Compared with the Other Glycopeptides.
Clinical Pharmacokinetics and Pharmacodynamics of Telavancin Compared with the Other Glycopeptides.
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DOI：
10.1007/s40262-017-0623-4
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发表时间：
2018-07
影响因子：
4.5
通讯作者：
Zeitlinger M
中科院分区：
文献类型：
--
作者：
Al Jalali V;Zeitlinger M
特拉万辛是通过修饰万古霉素的化学结构而发现的，属于脂糖肽类。它通过两种不同的作用机制发挥其抗菌潜力：抑制细菌细胞壁合成和诱导细菌膜去极化和渗透。本文综述了替拉万星的临床相关药代动力学和药效学资料。为了比较，本文给出了其他糖肽的药代动力学和药效学数据。尽管与较新的脂糖肽相比，telavancin表现出相对较短的半衰期和快速的总清除，但其表观分布体积（Vd）几乎与dalbavancin相同。重复给药后，特拉万星的积累只是边际的，而其他糖肽的药代动力学值在多次给药后显示出更大的差异。尽管telavancin的血浆蛋白结合率高达90%，Vd相对较低，约为11l，但血浆中游离部分与软组织接近完全平衡。未结合的血浆浓度-时间曲线下面积（AUC24）与特拉万星抑制90%的金黄色葡萄球菌和表皮葡萄球菌生长所需的最低抑制浓度（MIC）之比足够高，足以达到最佳细菌杀灭的药代动力学/药效学指标。考虑到特拉万星的AUC24/MIC比值以及血浆中游离部分与软组织的接近完全平衡，特拉万星是治疗革兰氏阳性病原体引起的软组织感染的合适抗菌药物。虽然特拉万星对上皮衬里液（ELF）的渗透还需要进一步的研究，但金黄色葡萄球菌的AUC24/MIC比值表明，在上皮衬里液中的杀菌活性是可以预期的。
Telavancin was discovered by modifying the chemical structure of vancomycin and belongs to the group of lipoglycopeptides. It employs its antimicrobial potential through two distinct mechanisms of action: inhibition of bacterial cell wall synthesis and induction of bacterial membrane depolarization and permeabilization. In this article we review the clinically relevant pharmacokinetic and pharmacodynamic data of telavancin. For comparison, the pharmacokinetic and pharmacodynamic data of the other glycopeptides are presented. Although, in contrast to the newer lipoglycopeptides, telavancin demonstrates a relatively short half-life and rapid total clearance, its apparent volume of distribution (Vd) is almost identical to that of dalbavancin. The accumulation of telavancin after repeated dosing is only marginal, whereas the pharmacokinetic values of the other glycopeptides show much greater differences after administration of multiple doses. Despite its high plasma–protein binding of 90% and relatively low Vd of approximately 11 L, telavancin shows near complete equilibration of the free fraction in plasma with soft tissue. The ratio of the area under the plasma concentration–time curve from time zero to 24 h (AUC24) of unbound plasma concentrations to the minimal inhibitory concentration (MIC) required to inhibit growth of 90% of organisms (MIC90) of Staphylococcus aureus and S. epidermidis of telavancin are sufficiently high to achieve pharmacokinetic/pharmacodynamic targets indicative for optimal bacterial killing. Considering both the AUC24/MIC ratios of telavancin and the near complete equilibration of the free fraction in plasma with soft tissue, telavancin is an appropriate antimicrobial agent to treat soft tissue infections caused by Gram-positive pathogens. Although the penetration of telavancin into epithelial lining fluid (ELF) requires further investigations, the AUC24/MIC ratio for S. aureus indicates that bactericidal activity in the ELF could be expected.
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