Polk R E, Sica D A, Kerkering T M, Kline B J, Patterson P M, Baggett J W
Antimicrob Agents Chemother. 1984 Sep;26(3):322-7. doi: 10.1128/AAC.26.3.322.
The pharmacokinetics of cefmenoxime were determined after a 30-min intravenous infusion of 15 mg/kg of total body weight to 33 adult subjects with normal renal function (CLCR, greater than 80 ml/min per 1.73 m2, group I), mild renal insufficiency (CLCR, 40 to 79 ml/min per 1.73 m2, group II), moderate renal insufficiency (CLCR, 10 to 39 ml/min per 1.73 m2, group III), or severe renal impairment, (CLCR, less than 10 ml/min per 1.73 m2, group IV) or to patients between hemodialysis (CLCR, less than 10 ml/min per 1.73 m2, group V). Concentrations of cefmenoxime in serum and urine were determined by high-pressure liquid chromatography, and serum concentrations were fit to a two-compartment model. There was no significant relationship between creatinine clearance and either peak serum concentrations or volume of distribution at steady state. Patients in group I excreted 81% of the dose into the urine within 24 h; recovery decreased with worsening renal function. The mean terminal half-lives in groups I to V were 1.06, 1.50, 3.55, 4.60, and 11.4 h, respectively. There were good linear relationships between creatinine clearance, and the elimination rate and total body clearance of cefmenoxime. Dosage recommendations for subjects with renal insufficiency are proposed.
对33名成年受试者进行研究,以确定头孢甲肟的药代动力学。这些受试者具有正常肾功能(肌酐清除率CLCR大于80ml/min/1.73m²,I组)、轻度肾功能不全(CLCR为40至79ml/min/1.73m²,II组)、中度肾功能不全(CLCR为10至39ml/min/1.73m²,III组)、重度肾功能损害(CLCR小于10ml/min/1.73m²,IV组),或处于血液透析期间的患者(CLCR小于10ml/min/1.73m²,V组)。对这些受试者静脉输注30分钟,剂量为15mg/kg体重。采用高压液相色谱法测定血清和尿液中头孢甲肟的浓度,并将血清浓度拟合为二室模型。肌酐清除率与血清峰浓度或稳态分布容积之间无显著关系。I组患者在24小时内将81%的剂量经尿液排出;随着肾功能恶化,回收率降低。I至V组患者的平均终末半衰期分别为1.06、1.50、3.55、4.60和11.4小时。肌酐清除率与头孢甲肟的消除率和总体清除率之间存在良好的线性关系。文中提出了肾功能不全受试者的给药建议。