Leehey D J, Braun B I, Tholl D A, Chung L S, Gross C A, Roback J A, Lentino J R
Department of Medicine, Veterans Affairs Hospital, Hines, IL 60141.
J Am Soc Nephrol. 1993 Jul;4(1):81-90. doi: 10.1681/ASN.V4181.
A randomized, controlled clinical trial was performed to determine whether individualized dosing by use of Bayesian pharmacokinetic modeling could decrease nephrotoxicity accosted with aminoglycoside therapy. Two hundred forty-three patients receiving aminoglycosides for suspected or proven infection were randomly assigned to one of three groups: usual physician-directed dosing (Group 1), pharmacist-assisted dosing (Group 2), or pharmacist-directed dosing (Group 3). Dosing in Groups 2 and 3 was based on a Bayesian pharmacokinetic dosing program, whereas Group 1 served as the control group. Individualized dosing resulted in higher mean postinfusion (peak) serum aminoglycoside levels, higher ratios of mean peak level to minimum inhibitory concentration (peak/MIC ratios), and a trend toward lower trough serum levels. Milligrams per dose were higher and number of doses per day was lower in the pharmacist-dosed groups. However, the incidence of nephrotoxicity (> or = 100% increase in serum creatinine) was not different among the three groups (16, 27, and 16% in Groups 1, 2, and 3, respectively). Similarly, severity of toxicity was not affected by the dosing intervention. Risk factors for toxicity included duration of therapy, shock, treatment with furosemide, older age, and liver disease. After controlling for these factors, the dosing intervention still had no effect on nephrotoxicity. It was concluded that Bayesian pharmacokinetic dosing did not decrease the risk of nephrotoxicity associated with aminoglycoside therapy.
进行了一项随机对照临床试验，以确定使用贝叶斯药代动力学模型进行个体化给药是否能降低氨基糖苷类药物治疗所致的肾毒性。243例因疑似或确诊感染而接受氨基糖苷类药物治疗的患者被随机分为三组之一：常规医生指导给药组（第1组）、药剂师辅助给药组（第2组）或药剂师指导给药组（第3组）。第2组和第3组的给药基于贝叶斯药代动力学给药程序，而第1组作为对照组。个体化给药导致输注后（峰值）血清氨基糖苷类药物平均水平更高、平均峰值水平与最低抑菌浓度之比（峰值/ MIC比值）更高，且谷值血清水平有降低趋势。药剂师给药组每剂毫克数更高，每日给药次数更低。然而，三组间肾毒性发生率（血清肌酐升高≥100%）并无差异（第1、2和3组分别为16%、27%和16%）。同样，毒性严重程度也未受给药干预影响。毒性危险因素包括治疗持续时间、休克、使用呋塞米治疗、年龄较大和肝病。在对这些因素进行控制后，给药干预对肾毒性仍无影响。得出的结论是，贝叶斯药代动力学给药并未降低与氨基糖苷类药物治疗相关的肾毒性风险。
