Matzke G R, McGory R W, Halstenson C E, Keane W F
Antimicrob Agents Chemother. 1984 Apr;25(4):433-7. doi: 10.1128/AAC.25.4.433.
The pharmacokinetics of vancomycin were characterized in 56 patients with different degrees of renal function after an intravenous dose of 18.4 +/- 4.7 mg kg-1 (mean +/- standard deviation). Seven subjects had a creatinine clearance (CLCR) of greater than 60 ml min-1 (group I), 13 had a CLCR of 10 to 60 ml min-1 (group II), and 36 had a CLCR of less than 10 ml min-1 (group III). Serial serum samples (range, 3 to 8) were collected during the 168 h after drug administration. The serum concentration-time profile in all patients demonstrated monoexponential decay. The mean half-lives were 9.1, 32.3, and 146.7 h in groups I, II, and III, respectively. A significant decline in serum clearance (CLS) was also noted (62.7 to 28.3 to 4.87 ml min-1 in groups I, II, and III, respectively). The steady-state volume of distribution varied from 0.72 to 0.90 liter kg-1. There was no significant relationship between the steady-state volume of distribution and CLCR. The observed relationship between CLS and CLCR (CLS = 3.66 + 0.689 CLCR; r = 0.8807) can be utilized to devise dosage schedules for patients with any degree of renal impairment. This relationship was utilized to develop a nomogram for initial and maintenance dosing of vancomycin.
在56例不同程度肾功能的患者静脉注射剂量为18.4±4.7mg/kg（均值±标准差）后，对万古霉素的药代动力学进行了研究。7名受试者的肌酐清除率（CLCR）大于60ml/min（I组），13名受试者的CLCR为10至60ml/min（II组），36名受试者的CLCR小于10ml/min（III组）。在给药后的168小时内采集了系列血清样本（范围为3至8份）。所有患者的血清浓度-时间曲线均呈现单指数衰减。I组、II组和III组的平均半衰期分别为9.1、32.3和146.7小时。还观察到血清清除率（CLS）显著下降（I组、II组和III组分别从62.7降至28.3再降至4.87ml/min）。稳态分布容积在0.72至0.90升/千克之间变化。稳态分布容积与CLCR之间无显著关系。观察到的CLS与CLCR之间的关系（CLS = 3.66 + 0.689CLCR；r = 0.8807）可用于为任何程度肾功能损害的患者制定给药方案。利用这种关系制定了万古霉素初始和维持给药的列线图。
