Zeitlinger Markus A, Traunmüller Friederike, Abrahim Aiman, Müller Michael R, Erdogan Zeynep, Müller Markus, Joukhadar Christian
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Int J Antimicrob Agents. 2007 Jan;29(1):44-50. doi: 10.1016/j.ijantimicag.2006.08.045.
Recent observations indicate that pharmacokinetics of beta-lactam antibiotics in the lung can be predicted by the use of concentration versus time profiles in peripheral soft tissues. If this observation is transferred to other classes of antimicrobials, measurement of antimicrobial concentrations in peripheral tissues would enable prediction of the pharmacokinetics of antimicrobials at the site of the respiratory tract infection. We set out to test the hypothesis that concentrations of the fluoroquinolone levofloxacin in the respiratory tract can be predicted on the basis of knowledge of its pharmacokinetics in peripheral soft tissues. After administration of a single intravenous dose of 500mg of levofloxacin, microdialysis was used to describe the concentration versus time profiles of levofloxacin in the interstitial space fluid of lung tissue of patients (n=5) undergoing elective lung surgery. These data were compared with the concentration versus time courses in the interstitial space fluid of skeletal muscle and subcutaneous adipose tissue of healthy volunteers (n=7). The median AUC(0-infinity) of free levofloxacin in lung (2267mg x min/L, 1980-2355) was about 2-fold and 1.5-fold lower compared with skeletal muscle (4381mg x min/L, range 1720-8195) and adipose tissue (3492mg x min/L, range 1323-6420) of healthy controls, respectively. Concentrations in the interstitial space fluid of the lung were descriptively lower compared with corresponding concentrations in peripheral soft tissues. This is in contrast to previous observations made for the class of beta-lactam antibiotics, and indicates that pharmacokinetics of levofloxacin derived from soft tissues may not be used uncritically for prediction of levofloxacin concentrations in the interstitium of the lung.
近期观察结果表明，通过外周软组织中浓度与时间曲线可预测β-内酰胺类抗生素在肺部的药代动力学。若这一观察结果适用于其他类别的抗菌药物，那么对外周组织中抗菌药物浓度的测定将有助于预测呼吸道感染部位抗菌药物的药代动力学。我们着手检验这样一个假设，即基于左氧氟沙星在周围软组织中的药代动力学知识，可预测其在呼吸道中的浓度。单次静脉注射500mg左氧氟沙星后，采用微透析法描述了接受择期肺部手术患者（n = 5）肺组织间质液中左氧氟沙星的浓度与时间曲线。将这些数据与健康志愿者（n = 7）骨骼肌和皮下脂肪组织间质液中的浓度与时间过程进行了比较。与健康对照者的骨骼肌（4381mg·min/L，范围1720 - 8195）和脂肪组织（3492mg·min/L，范围1323 - 6420）相比，肺组织中游离左氧氟沙星的中位AUC(0 - ∞)（2267mg·min/L，1980 - 2355）分别低约2倍和1.5倍。肺组织间质液中的浓度在描述上低于外周软组织中的相应浓度。这与先前对β-内酰胺类抗生素的观察结果相反，表明从软组织得出的左氧氟沙星药代动力学可能不能不加批判地用于预测肺间质中左氧氟沙星的浓度。
