PKPDyne, Inc., Gainesville, FL, USA.
Eur J Med Res. 2010 Nov 30;15(12):533-43. doi: 10.1186/2047-783x-15-12-533.
The rapid antibiotic resistance development has created a major demand for new antimicrobial agents that can combat resistant strains such as methicillin-resistant S. aureus (MRSA). Until a short time ago, the glycopeptide vancomycin was the only therapeutic choice in this situation. However, in recent years some newer agents with different mechanisms of actions have been added to the arsenal, and more are on the horizon. For a successful therapy it is of vital importance that these compounds are used judiciously and dosed appropriately. The present article reviews the pharmacokinetic properties of vancomycin, linezolid, tigecycline and daptomycin. The first major difference between these compounds is their oral bioavailability. Only linezolid can be administered orally, whereas vancomycin, daptomycin and tigecycline are limited to parenteral use. Once in the body, they show very different disposition. Daptomycin has a very small volume of distribution of 7L indicating very little tissue distribution whereas tigecycline has a very large volume of distribution of 350-500 L. Vancomycin and linezolid are in-between with volumes of distribution of approximately 30 and 50 L, close to total body water. However, studies have shown that linezolid shows better tissue penetration than vancomycin. Newer studies using microdialysis, a new technique that allows direct monitoring of unbound tissue levels, support this finding. As far as drug elimination, daptomycin and vancomycin are mainly eliminated into the urine and require dosing adjustments in renally impaired patients, whereas tigecycline is eliminated into the bile and linezolid is metabolized so that in renal patients no dosing adjustments are needed for these compounds. Although the elimination pathways are very different, the resulting half-lives of linezolid, vancomycin, and daptomycin are not greatly different and vary from 4-8 h. Tigecycline, however, has a much longer half-life of up to 1-2 days due to the slow redistribution from tissue binding sites.
抗生素耐药性的迅速发展，对能够对抗耐甲氧西林金黄色葡萄球菌（MRSA）等耐药菌株的新型抗菌药物产生了巨大需求。直到不久前，糖肽类万古霉素还是这种情况下的唯一治疗选择。然而，近年来，一些具有不同作用机制的新型药物已被加入到武器库中，而且更多的药物正在研发之中。为了获得成功的治疗效果，这些化合物的使用必须慎重且剂量恰当。本文综述了万古霉素、利奈唑胺、替加环素和达托霉素的药代动力学特性。这些化合物的第一个主要区别是它们的口服生物利用度。只有利奈唑胺可以口服给药，而万古霉素、达托霉素和替加环素则仅限于注射给药。进入体内后，它们的分布情况也大不相同。达托霉素的分布容积非常小，只有 7L，表明其组织分布非常有限，而替加环素的分布容积则非常大，为 350-500L。万古霉素和利奈唑胺则处于两者之间，分布容积约为 30 和 50L，接近全身水。然而，研究表明，利奈唑胺比万古霉素具有更好的组织穿透性。使用微透析的新研究，一种允许直接监测未结合组织水平的新技术，支持了这一发现。至于药物消除，达托霉素和万古霉素主要通过尿液消除，因此需要在肾功能受损的患者中调整剂量，而替加环素则通过胆汁消除，利奈唑胺则被代谢，因此在肾功能受损的患者中无需调整这些药物的剂量。尽管消除途径非常不同，但利奈唑胺、万古霉素和达托霉素的半衰期并没有太大差异，约为 4-8 小时。然而，替加环素的半衰期要长得多，可达 1-2 天，这是由于其从组织结合部位的缓慢再分布所致。
