抗生素在组织中的扩散系数的测量及其临床和药代动力学意义
Measurement and clinical and pharmacokinetic implications of diffusion coefficients of antibiotics in tissues.
作者信息
Meulemans A, Paycha F, Hannoun P, Vulpillat M
机构信息
Laboratoire de Biophysique, Faculté de Médecine Xavier-Bichat, Paris, France.
出版信息
Antimicrob Agents Chemother. 1989 Aug;33(8):1286-90. doi: 10.1128/AAC.33.8.1286.
A method for determining diffusion coefficients of four antibiotics in extracellular tissue space according to Fick's law is described. This new method was applied to rat brain tissue and to agar. After diffusion of the antibiotic in one axis, the gradient concentration was determined with microvoltammetric electrodes. These microelectrodes (1 micron at the extreme tip) measured the free diffusible form of electroactive antibiotics in the extracellular brain space. Metronidazole, chloramphenicol succinate, cefsulodin, and piperacillin gave diffusion coefficients ranging from 0.1 x 10(-6) to 0.2 x 10(-6) cm2 . s-1 in tissue; chloramphenicol base, which is positively charged, gave a coefficient of 0.04 x 10(-6) cm2 . s-1. The coefficient ranged from 0.6 x 10(-6) to 1.2 x 10(-6) cm2 . s-1 in agar. These coefficients were used to simulate antibiotic concentrations in infectious sites and between capillaries by using a simple model of plane diffusion.
描述了一种根据菲克定律测定四种抗生素在细胞外组织间隙中扩散系数的方法。该新方法应用于大鼠脑组织和琼脂。抗生素在一个轴向上扩散后，用微伏安电极测定浓度梯度。这些微电极（尖端为1微米）测量细胞外脑间隙中电活性抗生素的游离可扩散形式。甲硝唑、琥珀氯霉素、头孢磺啶和哌拉西林在组织中的扩散系数范围为0.1×10⁻⁶至0.2×10⁻⁶ cm²·s⁻¹；带正电荷的氯霉素碱的扩散系数为0.04×10⁻⁶ cm²·s⁻¹。在琼脂中的扩散系数范围为0.6×10⁻⁶至1.2×10⁻⁶ cm²·s⁻¹。通过使用平面扩散的简单模型，这些系数被用于模拟感染部位和毛细血管之间的抗生素浓度。
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