MacDonald N E, Anas N G, Peterson R G, Schwartz R H, Brooks J G, Powell K R
J Pediatr. 1983 Dec;103(6):985-90. doi: 10.1016/s0022-3476(83)80737-9.
This study was designed to corroborate previous observations of low serum concentrations of aminoglycosides after usual doses in patients with cystic fibrosis and to investigate possible mechanisms for this change. We studied gentamicin clearance after single and multiple intravenously administered doses in 10 non-acutely ill patients with mild to moderate CF. The data could best be described by a two-compartment model for drug elimination. The mean 1-hour serum concentration, mean volume of distribution, and mean total plasma clearance of gentamicin were not different from those reported for patients without CF. The similarity of the plasma and the renal gentamicin clearances, supported by the observations that greater than 80% of administered drug was excreted in the urine by 4 hours and that negligible amounts were detected in sweat, saliva, or sputum, implies that the kidney is the major route of elimination in patients with mild CF. The correlation of increased plasma gentamicin clearance as NIH score decreases supports the hypothesis that aminoglycoside pharmacokinetics are changed as the severity of disease increases. For patients with mild CF, standard doses of gentamicin (60 mg/m2) will give safe and therapeutic concentrations.
本研究旨在证实先前关于囊性纤维化患者在使用常规剂量后血清氨基糖苷类药物浓度较低的观察结果，并探究这种变化的可能机制。我们研究了10例轻度至中度CF的非急性病患者单次及多次静脉注射庆大霉素后的清除情况。数据最好用二室药物消除模型来描述。庆大霉素的平均1小时血清浓度、平均分布容积和平均总血浆清除率与无CF患者报告的情况无差异。血浆和肾脏庆大霉素清除率的相似性，以及在4小时内超过80%的给药药物经尿液排出且在汗液、唾液或痰液中检测到的量可忽略不计的观察结果，表明肾脏是轻度CF患者的主要消除途径。随着NIH评分降低血浆庆大霉素清除率增加的相关性支持了随着疾病严重程度增加氨基糖苷类药物药代动力学发生变化的假设。对于轻度CF患者，标准剂量的庆大霉素（60mg/m²）将产生安全且有效的浓度。
