Ceftriaxone is widely used for respiratory and urinary infections in elderly and frail patients, but there are few pharmacokinetic studies. A prospective population pharmacokinetic study of ceftriaxone in adults over 65 years old was undertaken. Dried blood spots collected at baseline (predose) and 0.5, 1, 4, 8, and 24 h after administration of 1 g of ceftriaxone were assayed using a validated liquid chromatography-mass spectroscopy analytical method. Frailty was classified using the Edmonton frailty scale and grip strength via a hand dynamometer. Estimates of glomerular filtration rate were determined using creatinine-based and cystatin C-based equations. Of 26 patients recruited, 23 (88%) were vulnerable or very frail. Estimates of drug clearance improved significantly with a cystatin C-based estimate of renal function that accounted for frailty. Simulations indicate that the combined effects of ranges of size and renal function resulted in a 6-fold range in peak ceftriaxone concentrations and 9-fold range in total exposure (area under the concentration-time curve [AUC]). For elderly patients with moderate or severe renal impairment, 48-h dosing results in greater trough concentrations and total exposure than the trough concentrations and total exposure in patients with normal renal function receiving 24-h dosing. Cystatin C-based measures of renal function improved predictions of ceftriaxone clearance in elderly patients.

中文翻译：

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头孢曲松在老年患者中的群体药代动力学研究，使用基于胱抑素C的肾功能估计值来评估衰弱。

头孢曲松广泛用于老年人和体弱患者的呼吸道和泌尿道感染，但很少有药代动力学研究。进行了头孢曲松在65岁以上成年人中的前瞻性人群药代动力学研究。使用经过验证的液相色谱-质谱分析法，对在基线（给药前）和给药1 g头孢曲松钠后0.5、1、4、8和24 h收集的干血斑进行测定。使用埃德蒙顿（Edmonton）脆弱量表和通过测功机的握力对脆弱程度进行分类。肾小球滤过率的估计是使用基于肌酐和半胱氨酸蛋白酶抑制剂C的方程式确定的。在招募的26位患者中，有23位（88％）脆弱或非常脆弱。基于半胱氨​​酸蛋白酶抑制剂C评估的肾功能虚弱，估计药物清除率显着提高。模拟表明，大小和肾功能范围的综合作用导致头孢曲松钠峰值浓度增加6倍，总暴露量增加9倍（浓度-时间曲线[AUC]下的面积）。对于中度或重度肾功能不全的老年患者，与接受24小时给药的肾功能正常的患者相比，48小时给药导致的谷浓度和总暴露量更高。基于胱抑素C的肾功能指标可改善老年患者头孢曲松清除率的预测。对于中度或重度肾功能不全的老年患者，与接受24小时给药的肾功能正常的患者相比，48小时给药导致的谷浓度和总暴露量更高。基于胱抑素C的肾功能指标可改善老年患者头孢曲松清除率的预测。对于中度或重度肾功能不全的老年患者，与接受24小时给药的肾功能正常的患者相比，48小时给药导致的谷浓度和总暴露量更高。基于胱抑素C的肾功能指标可改善老年患者头孢曲松清除率的预测。