Kempker Russell R, Barth Aline B, Vashakidze Sergo, Nikolaishvili Ketino, Sabulua Irina, Tukvadze Nestani, Bablishvili Nino, Gogishvili Shota, Singh Ravi Shankar P, Guarner Jeannette, Derendorf Hartmut, Peloquin Charles A, Blumberg Henry M
Division of Infectious Diseases Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
University of Florida, College of Pharmacy, Gainesville, Florida, USA.
Antimicrob Agents Chemother. 2015;59(6):3149-55. doi: 10.1128/AAC.00379-15. Epub 2015 Mar 16.
A better understanding of second-line drug (SLD) pharmacokinetics, including cavitary penetration, may help optimize SLD dosing. Patients with pulmonary multidrug-resistant tuberculosis (MDR-TB) undergoing adjunctive surgery were enrolled in Tbilisi, Georgia. Serum was obtained at 0, 1, 4, and 8 h and at the time of cavitary removal to measure levofloxacin concentrations. After surgery, microdialysis was performed using the ex vivo cavity, and levofloxacin concentrations in the collected dialysate fluid were measured. Noncompartmental analysis was performed, and a cavitary-to-serum levofloxacin concentration ratio was calculated. Twelve patients received levofloxacin for a median of 373 days before surgery (median dose, 11.8 mg/kg). The median levofloxacin concentration in serum (Cmax) was 6.5 μg/ml, and it was <2 μg/ml in 3 (25%) patients. Among 11 patients with complete data, the median cavitary concentration of levofloxacin was 4.36 μg/ml (range, 0.46 to 8.82). The median cavitary/serum levofloxacin ratio was 1.33 (range, 0.63 to 2.36), and 7 patients (64%) had a ratio of >1. There was a significant correlation between serum and cavitary concentrations (r = 0.71; P = 0.01). Levofloxacin had excellent penetration into chronic cavitary TB lesions, and there was a good correlation between serum and cavitary concentrations. Optimizing serum concentrations will help ensure optimal cavitary concentrations of levofloxacin, which may enhance treatment outcomes.
更好地了解二线药物（SLD）的药代动力学，包括空洞穿透情况，可能有助于优化二线药物的给药剂量。在格鲁吉亚的第比利斯，对接受辅助手术的耐多药肺结核（MDR-TB）患者进行了研究。分别在0、1、4和8小时以及空洞切除时采集血清，以测量左氧氟沙星浓度。术后，使用离体空洞进行微透析，并测量收集的透析液中的左氧氟沙星浓度。进行了非房室分析，并计算了空洞与血清左氧氟沙星浓度之比。12例患者在手术前接受左氧氟沙星治疗的中位时间为373天（中位剂量为11.8mg/kg）。血清中左氧氟沙星的中位浓度（Cmax）为6.5μg/ml，3例（25%）患者的浓度<2μg/ml。在11例有完整数据的患者中，左氧氟沙星的中位空洞浓度为4.36μg/ml（范围为0.46至8.82）。左氧氟沙星的中位空洞/血清浓度比为1.33（范围为0.63至2.36），7例（64%）患者的比值>1。血清浓度与空洞浓度之间存在显著相关性（r = 0.71；P = 0.01）。左氧氟沙星对慢性空洞性结核病灶具有良好的穿透性，血清浓度与空洞浓度之间具有良好的相关性。优化血清浓度将有助于确保左氧氟沙星在空洞中的最佳浓度，这可能会提高治疗效果。
