Tsai Danny, Jamal Janattul-Ain, Davis Joshua S, Lipman Jeffrey, Roberts Jason A
Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Level 3, Ned Hanlon Building, Royal Brisbane and Women's Hospital, Herston, Brisbane, QLD, 4029, Australia.
Clin Pharmacokinet. 2015 Mar;54(3):243-60. doi: 10.1007/s40262-014-0209-3.
Optimal antibacterial dosing is imperative for maximising clinical outcome. Many factors can contribute to changes in the pharmacokinetics of antibacterials to the extent where dose adjustment may be needed. In acute illness, substantial changes in important pharmacokinetic parameters such as volume of distribution and clearance can occur for certain antibacterials. The possibility of interethnic pharmacokinetic differences can further complicate attempts to design an appropriate dosing regimen. Factors of ethnicity, such as genetics, body size and fat distribution, contribute to differences in absorption, distribution, metabolism and elimination of drugs. Despite extensive previous work on the altered pharmacokinetics of antibacterials in some patient groups such as the critically ill, knowledge of interethnic pharmacokinetic differences for antibacterials is limited.
This systematic review aims to describe any pharmacokinetic differences in antibacterials between different ethnic groups, and discuss their probable mechanisms as well as any clinical implications.
We performed a structured literature review to identify and describe available data of the interethnic differences in the pharmacokinetics of antibacterials.
We found 50 articles that met our inclusion criteria and only six of these compared antibacterial pharmacokinetics between different ethnicities within the same study. Overall, there was limited evidence available. We found that interethnic pharmacokinetic differences are negligible for carbapenems, most β-lactams, aminoglycosides, glycopeptides, most fluoroquinolones, linezolid and daptomycin, whereas significant difference is likely for ciprofloxacin, macrolides, clindamycin, tinidazole and some cephalosporins. In general, subjects of Asian ethnicity achieve drug exposures up to two to threefold greater than Caucasian counterparts for these antibacterials. This difference is caused by a comparatively lower volume of distribution and/or drug clearance.
Interethnic pharmacokinetic differences of antibacterials are likely; however, the clinical relevance of these differences is unknown and warrants further research.
优化抗菌药物剂量对于实现最佳临床疗效至关重要。许多因素可导致抗菌药物药代动力学发生变化，以至于可能需要调整剂量。在急性疾病中，某些抗菌药物的重要药代动力学参数（如分布容积和清除率）可能会发生显著变化。种族间药代动力学差异的可能性会使设计合适给药方案的尝试变得更加复杂。种族因素，如遗传学、体型和脂肪分布，会导致药物吸收、分布、代谢和消除的差异。尽管此前在一些患者群体（如危重症患者）中对抗菌药物药代动力学改变进行了大量研究，但关于抗菌药物种族间药代动力学差异的知识仍然有限。
本系统评价旨在描述不同种族之间抗菌药物的药代动力学差异，讨论其可能机制以及任何临床意义。
我们进行了结构化文献综述，以识别和描述抗菌药物药代动力学种族间差异的现有数据。
我们发现50篇文章符合纳入标准，其中只有6篇在同一研究中比较了不同种族之间的抗菌药物药代动力学。总体而言，现有证据有限。我们发现，碳青霉烯类、大多数β-内酰胺类、氨基糖苷类、糖肽类、大多数氟喹诺酮类、利奈唑胺和达托霉素的种族间药代动力学差异可忽略不计，而环丙沙星、大环内酯类、克林霉素、替硝唑和一些头孢菌素类药物可能存在显著差异。一般来说，对于这些抗菌药物，亚洲种族受试者的药物暴露量比白种人受试者高两到三倍。这种差异是由相对较低的分布容积和/或药物清除率引起的。
抗菌药物可能存在种族间药代动力学差异；然而，这些差异的临床相关性尚不清楚，值得进一步研究。
