Pechere J C, Dugal R, Pechere M M
Clin Pharmacokinet. 1978 Sep-Oct;3(5):395-406. doi: 10.2165/00003088-197803050-00005.
The pharmacokinetics of intravenously administered netilmicin, an investigational aminoglycoside antibiotic, were studied in 38 patients with creatinine clearance ranging from 150 to Oml/min/1.73m2 in order to determine the influence of kidney function status on the disposition of the antibiotic. The serum disappearance of netilmicin followed first order kinetics and the elimination rate constant decreased proportionally with decreasing renal function. Half-lives averaged 2.2 hours in normal individuals (creatinine clearance greater than 80ml/min/1.73m2) and reached 42 +/- 10 hours (mean +/- SD) in virtually anephric patients. The elimination rate constant lowered proportionally with decreasing renal function. Several linear relationships between pharmacokinetic parameters and renal function indicators were defined. A clinically useful correlation indicates that the half-life may be approximated as 3 times the serum creatinine concentration and may be used for adjustment of dosage of netilmicin in the treatment of patients with impaired renal function. During haemodialysis, netilmicin extraction from the blood reaches 75 +/- 14% (mean +-/ 95% confidence interval) of that of creatinine and 88 +/- 19% of that of blood urea nitrogen.
为了确定肾功能状态对一种研究性氨基糖苷类抗生素奈替米星处置的影响,在38例肌酐清除率为150至0ml/分钟/1.73平方米的患者中研究了静脉注射奈替米星的药代动力学。奈替米星的血清消除遵循一级动力学,消除速率常数随肾功能下降而呈比例降低。正常个体(肌酐清除率大于80ml/分钟/1.73平方米)的半衰期平均为2.2小时,而在几乎无肾的患者中达到42±10小时(平均值±标准差)。消除速率常数随肾功能下降而呈比例降低。定义了药代动力学参数与肾功能指标之间的几种线性关系。一种临床有用的相关性表明,半衰期大约可以是血清肌酐浓度的3倍,可用于肾功能受损患者治疗中奈替米星剂量的调整。在血液透析期间,奈替米星从血液中的清除率达到肌酐清除率的75±14%(平均值±95%置信区间)和血尿素氮清除率的88±19%。