Ciprofloxacin is highly active against bacteria that commonly cause bone infections. However, the time-course of ciprofloxacin in bone has not been characterized using population pharmacokinetic modeling. Thirty-nine patients received a 1-h infusion of 400 mg of ciprofloxacin before orthopedic surgery. Blood and bone samples were collected at 0.5 to 20 h following the start of the infusion. Bone samples were separated into cortical and cancellous bone and pulverized under liquid nitrogen using a cryogenic mill. Ciprofloxacin in plasma, and cortical and cancellous bone was quantified by liquid chromatography–tandem mass spectrometry. A physiologically based pharmacokinetic modeling approach was utilized to describe the concentration–time profiles in plasma and bone. Ciprofloxacin concentrations ranged from 0.176 to 5.98 mg/L (median, 1.67; density, 1.99 g/cm³) in cortical, and 0.224 to 14.6 mg/L (median, 1.22; 1.92 g/cm³) in cancellous bone. The average observed cortical bone/plasma concentration ratio was 0.67 at 0.5 to 2 h (n = 7) and 5.1 at 13 to 20 h (n = 9). For cancellous bone the respective average ratios were 0.77 and 4.4. The population PK model included a central (blood) compartment, two peripheral tissue compartments, and compartments for the organic and inorganic (hydroxyapatite) matrix in cortical and cancellous bone. The population mean ciprofloxacin clearance was 20.7 L/h. The estimated partition coefficients of the organic bone matrix were 3.39 for cortical and 5.11 for cancellous bone. Ciprofloxacin achieved higher concentrations in bone than plasma. Slow redistribution from bone to plasma may have been due to binding to the inorganic bone matrix. The developed model presents a step toward optimized antibiotic dosing in osteomyelitis.

中文翻译：

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骨科手术患者环丙沙星的基于生理的群体药代动力学建模方法。

环丙沙星对通常引起骨骼感染的细菌具有很高的活性。然而，尚未使用群体药代动力学模型表征骨中环丙沙星的时程。三十九名患者在整形外科手术前接受了400毫克环丙沙星的1小时输注。输注开始后0.5至20 h采集血液和骨骼样本。将骨样品分离为皮质和松质骨，并在液氮下使用低温研磨机粉碎。血浆，皮质和松质骨中的环丙沙星通过液相色谱-串联质谱法定量。基于生理学的药代动力学建模方法用于描述血浆和骨骼中的浓度-时间曲线。环丙沙星浓度范围为0.176至5.98 mg / L（中位数为1.67；密度为³）在皮质中，在松质骨中为0.224至14.6 mg / L（中位数为1.22； 1.92 g / cm ³）。平均观察到的皮质骨/血浆浓度比在0.5至2 h（n = 7）为0.67，在13至20 h（n为7）= 9）。对于松质骨，各自的平均比率为0.77和4.4。总体PK模型包括一个中央（血液）腔室，两个外围组织腔室以及皮质和松质骨中有机和无机（羟基磷灰石）基质的腔室。人口平均环丙沙星清除率为20.7 L / h。估计的有机骨基质分配系数对于皮质为3.39，对于松质骨为5.11。环丙沙星在骨骼中的浓度高于血浆。从骨头到血浆的缓慢重新分布可能是由于与无机骨基质的结合所致。开发的模型为骨髓炎中抗生素剂量的优化迈出了一步。