Santos Martínez Martínez María, Colino Gandarillas Clara Isabel, Lanao José Martínez, Sánchez Navarro Amparo
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Salamanca, Avda. Campo Charro s/n, 37007 Salamanca, Spain.
Eur J Pharm Sci. 2005 Mar;24(4):325-32. doi: 10.1016/j.ejps.2004.11.008. Epub 2005 Jan 19.
The objective of this study was to examine the influence of the rate at which the tissue is perfused on the disposition of levofloxacin and netilmicin in the pulmonary tissue, using an experimental model of the isolated rat lung. Analysis of the results was performed using two pharmacokinetic approaches. By stochastic analysis of outflow curves the corresponding statistical moments and derived distribution coefficient were calculated. Model-dependent analysis based on a three-compartment dispersion model was also applied to the outflow concentration data. A statistically significant decrease in the distribution coefficient was observed for both antibiotics when the flow rate was decreased. For levofloxacin this parameter takes values of 2.14 and 1.25 mL/g for 10 and 5 mL/min flow rates, respectively. In the case of netilmicin these values were 0.81 and 0.39 mL/g for the higher and lower flow rates, respectively. Model parameters related to the distribution process were also modified as a consequence of the flow rate decrease. Tissue flow rate seems to be a determinant factor on the distribution of levofloxacin and netilmicin in the isolated rat lung.
本研究的目的是使用离体大鼠肺实验模型，研究组织灌注速率对左氧氟沙星和奈替米星在肺组织中处置的影响。使用两种药代动力学方法对结果进行分析。通过对流出曲线的随机分析，计算相应的统计矩和导出的分布系数。基于三室分散模型的模型依赖性分析也应用于流出浓度数据。当流速降低时，两种抗生素的分布系数均出现统计学显著下降。对于左氧氟沙星，该参数在流速为10和5 mL/min时分别取值2.14和1.25 mL/g。对于奈替米星，在较高和较低流速下这些值分别为0.81和0.39 mL/g。由于流速降低，与分布过程相关的模型参数也发生了改变。组织流速似乎是左氧氟沙星和奈替米星在离体大鼠肺中分布的决定因素。
