Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan.
J Clin Pharmacol. 2013 Sep;53(9):967-73. doi: 10.1002/jcph.133.
Linezolid has antibacterial activity against aerobic Gram-positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA). Adjustment of the dose of linezolid has been proposed to be unnecessary in patients with reduced renal function. However, platelet counts and hemoglobin levels were shown to be significantly lower in such patients than in patients with normal renal function. The population pharmacokinetic (PPK) of linezolid was investigated in MRSA infected patients with renal dysfunction. Linezolid concentrations in serum were measured by high-performance liquid chromatography. PPK analysis was performed in the nonlinear mixed effects model (NONMEM) computer program. In the final PPK model, total body weight (TBW), estimated glomerular filtration rate (eGFR), hemoglobin (HB), and alanine amino transferase (ALT) were influential covariates on total body clearance (CL), and the volume of distribution (Vd) was affected by TBW, which was expressed as CL (L/h) = 0.00327 × TBW × eGFR(0.428) × HB(0.502) × 0.283 (ALT ≥ 100 IU/L) and CL (L/h) = 0.00327 × TBW × eGFR(0.428) × HB(0.502) (ALT < 100 IU/L), Vd (L) = 1.310 × TBW. The PPK parameters of linezolid obtained here are useful for the optimal use of linezolid with similar patient population characteristics.
利奈唑胺对需氧革兰氏阳性球菌具有抗菌活性，包括耐甲氧西林金黄色葡萄球菌（MRSA）。建议肾功能减退的患者无需调整利奈唑胺的剂量。然而，与肾功能正常的患者相比，此类患者的血小板计数和血红蛋白水平明显较低。对肾功能障碍的耐甲氧西林金黄色葡萄球菌感染患者进行了利奈唑胺的群体药代动力学（PPK）研究。采用高效液相色谱法测定血清中的利奈唑胺浓度。采用非线性混合效应模型（NONMEM）计算机程序进行 PPK 分析。在最终的 PPK 模型中，总体重（TBW）、估计肾小球滤过率（eGFR）、血红蛋白（HB）和丙氨酸氨基转移酶（ALT）是总清除率（CL）的有影响的协变量，而分布容积（Vd）受 TBW 影响，可表示为 CL（L/h）=0.00327×TBW×eGFR（0.428）×HB（0.502）×0.283（ALT≥100IU/L）和 CL（L/h）=0.00327×TBW×eGFR（0.428）×HB（0.502）（ALT<100IU/L），Vd（L）=1.310×TBW。此处获得的利奈唑胺 PPK 参数可用于具有类似患者群体特征的利奈唑胺的最佳使用。
