Autret E, Marchand S, Breteau M, Grenier B
Eur J Clin Pharmacol. 1986;31(1):79-83. doi: 10.1007/BF00870991.
36 pharmacokinetic studies of amikacin were performed to evaluate the bronchial diffusion of amikacin in 9 children with cystic fibrosis, 3 to 15 years old. Amikacin was administered i.v. according to a variable dosage regimen. Four children without cystic fibrosis were enrolled as controls. The mean half life was 1.1, the volume of distribution averaged 0.26 l/kg, and the mean plasma clearance was 131 ml/min/1.73 m2, which no differed from that of the controls. The mean peak plasma concentration was always above the MIC but its level depended on the unit dose: 18.5 mg/l, 25,95 mg/l and 31,46 mg/l for doses of 5, 7.5 and 12.5 mg/kg, respectively. Between consecutive amikacin infusions, the plasma level was above the MIC for 21% and 46% of the time after the 5 and 7.5 mg/kg doses. The maximum concentration in sputum between H1 and H2 was always below the MIC, except after 15 mg/kg. The ratio AUC sputum/AUC plasma was between 0.028 and 0.61, and it increased from the beginning to the end of the course of treatment. No side effects were observed on hearing, or vestibular and renal function. The results are used to suggest more appropriate dosing regimens.
对9名3至15岁的囊性纤维化患儿进行了36次阿米卡星的药代动力学研究,以评估阿米卡星在支气管中的扩散情况。根据可变剂量方案静脉注射阿米卡星。招募了4名无囊性纤维化的儿童作为对照。平均半衰期为1.1,分布容积平均为0.26升/千克,平均血浆清除率为131毫升/分钟/1.73平方米,与对照组无差异。平均血浆峰浓度始终高于最低抑菌浓度(MIC),但其水平取决于单位剂量:5、7.5和12.5毫克/千克剂量时分别为18.5毫克/升、25.95毫克/升和31.46毫克/升。在连续输注阿米卡星之间,5毫克/千克和7.5毫克/千克剂量后,血浆水平高于MIC的时间分别为21%和46%。除15毫克/千克剂量后外,H1和H2之间痰液中的最大浓度始终低于MIC。痰液AUC/血浆AUC之比在0.028至0.61之间,且在治疗过程中从开始到结束逐渐增加。未观察到对听力、前庭和肾功能的副作用。这些结果用于建议更合适的给药方案。