Kiang Tony K L, Häfeli Urs O, Ensom Mary H H
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.
Clin Pharmacokinet. 2014 Aug;53(8):695-730. doi: 10.1007/s40262-014-0152-3.
The objective of the current review was to provide an updated and comprehensive summary on pharmacokinetic data describing the distribution of antimicrobials into interstitial fluid (ISF) by comparing drug concentration versus time profiles between ISF and blood/plasma in healthy individuals and/or diseased populations. An extensive literature search identified 55 studies detailing 87 individual comparisons. For each antibiotic (antibacterial) (or antibiotic class), we comment on dosing implications based on tissue ISF distribution characteristics and determine the suitability of conducting clinical pharmacokinetic monitoring (CPM) using a previously published scoring algorithm. Using piperacillin as an example, there is evidence supporting different degrees of drug penetration into the ISF of different tissues. A higher dose of piperacillin may be required to achieve an adequate ISF concentration in soft tissue infections. To achieve these higher doses, alternative administration regimens such as intravenous infusions may be utilized. Data also suggest that piperacillin can be categorized as a 'likely suitable' agent for CPM in ISF. Regression analyses of data from the published studies, including protein binding, molecular weight, and predicted partition coefficient (using XlogP3) as dependent variables, indicated that protein binding was the only significant predictor for the extent of drug distribution as determined by ratios of the area under the concentration-time curve between muscle ISF/total plasma (R (2) = 0.65, p < 0.001) and adipose ISF/total plasma (R (2) = 0.48, p < 0.004). Although recurrent limitations (i.e., small sample size, lack of statistical comparisons, lack of steady-state conditions, high individual variability) were identified in many studies, these data are still valuable and allowed us to generate general dosing guidelines and assess the suitability of using ISF for CPM.
本综述的目的是通过比较健康个体和/或患病群体中间质液（ISF）与血液/血浆的药物浓度-时间曲线，提供关于抗菌药物在间质液中分布的药代动力学数据的最新综合总结。广泛的文献检索确定了55项研究，详细列出了87项个体比较。对于每种抗生素（抗菌药物）（或抗生素类别），我们根据组织ISF分布特征对给药影响进行评论，并使用先前发表的评分算法确定进行临床药代动力学监测（CPM）的适用性。以哌拉西林为例，有证据支持不同程度的药物渗透到不同组织的ISF中。在软组织感染中，可能需要更高剂量的哌拉西林才能达到足够的ISF浓度。为了达到这些更高的剂量，可以采用替代给药方案，如静脉输注。数据还表明，哌拉西林可被归类为ISF中CPM的“可能合适”药物。对已发表研究的数据进行回归分析，包括将蛋白结合、分子量和预测分配系数（使用XlogP3）作为自变量，结果表明，蛋白结合是药物分布程度的唯一重要预测因素，通过肌肉ISF/总血浆（R² = 0.65，p < 0.001）和脂肪ISF/总血浆（R² = 0.48，p < 0.004）之间的浓度-时间曲线下面积比来确定。尽管在许多研究中发现了反复出现的局限性（即样本量小、缺乏统计比较、缺乏稳态条件、个体变异性高），但这些数据仍然有价值，使我们能够制定一般给药指南并评估使用ISF进行CPM的适用性。
