Motohiro T, Tanaka K, Kawakami A, Koga T, Shimada Y, Tomita S, Sakata Y, Fujimoto T, Nishiyama T, Kuda N
Department of Pediatrics, School of Medicine, Kurume University.
Jpn J Antibiot. 1987 Jun;40(6):1200-14.
To evaluate pharmacokinetics of amikacin (AMK), one of the aminoglycoside antibiotics, children with ages from 2 days to 11 years were treated with various doses by various administration routes, and both plasma and urinary levels of AMK were determined. The following is a summary of the results obtained: 1. Of 6 children, three were treated with 2.0 mg/kg of AMK by a 30-minute intravenous drip infusion, and the other 3 with 4.0 mg/kg by a 60-minute. Peaks of average plasma levels were observed at the ends of the infusions in both cases, and their levels were 9.23 and 13.67 micrograms/ml, respectively, showing a dose-dependency. Both half-lives and areas under plasma concentration-time curves (AUCs) were similar to those of adults. However, the volume of distribution (Vd) showed a lower value than that of adults. Peaks of average urine levels were 149.3 micrograms/ml with 2.0 mg/kg in 0-2 hours after the start of the infusion and 223.3 micrograms/ml with 4.0 mg/kg in 2-4 hours. Average urinary recovery rates within 6 hours after the start of the infusion were 95.4% with 2.0 mg/kg and 85.7% with 4.0 mg/kg. These recoveries were equal to or higher than that of adults. 2. When 3.0, 4.0 and 6.0 mg/kg of AMK were administered to 3 groups of mature or premature babies by intramuscular injection, average peak levels of AMK in plasma were 6.26, 8.61 and 12.60 micrograms/ml, respectively, at 30 minutes after the injection, showing dose-dependency. In these groups, the younger the day age after birth was, the longer the half-life became. The AUCs were larger as the half-life became longer. The Vd was larger than that in the intravenous drip infusion group, but, any particular was not observed. Average peak levels of AMK in urine were 78.83 micrograms/ml at 4-6 hours with a dose level of 3.0 mg/kg, 99.17 micrograms/ml at 2-4 hours with 4.0 mg/kg and 139.20 micrograms/ml at 0-2 hours with 6.0 mg/kg. Average urinary recovery rates within 6 hours were 36.57% with 3.0 mg/kg, 34.67% with 4.0 mg/kg and 43.77% with 6.0 mg/kg. These recovery rates were markedly lower than those observed in adults and children. One of the causes of this low recovery is that mature and premature babies have immature renal functions. 3. When 3.0 mg/kg of AMK was administered to three premature babies by a 30-minute intravenous drip infusion, the average peak plasma levels was 7.61 micrograms/ml at the end of the drip infusion.(ABSTRACT TRUNCATED AT 400 WORDS)
为评估氨基糖苷类抗生素之一的阿米卡星（AMK）的药代动力学，对年龄在2天至11岁的儿童采用不同给药途径给予不同剂量的药物，并测定血浆和尿液中AMK的水平。以下是所得结果的总结：1. 6名儿童中，3名儿童通过30分钟静脉滴注给予2.0mg/kg的AMK，另外3名儿童通过60分钟静脉滴注给予4.0mg/kg的AMK。两种情况下，平均血浆水平峰值均在输注结束时观察到，其水平分别为9.23和13.67微克/毫升，呈现剂量依赖性。半衰期和血浆浓度-时间曲线下面积（AUC）均与成人相似。然而，分布容积（Vd）的值低于成人。输注开始后0至2小时，2.0mg/kg剂量组的平均尿液水平峰值为149.3微克/毫升；2至4小时，4.0mg/kg剂量组的平均尿液水平峰值为223.3微克/毫升。输注开始后6小时内的平均尿回收率，2.0mg/kg剂量组为95.4%，4.0mg/kg剂量组为85.7%。这些回收率等于或高于成人。2. 对3组成熟或早产婴儿肌肉注射3.0、4.0和6.0mg/kg的AMK时，注射后30分钟血浆中AMK的平均峰值水平分别为6.26、8.61和12.60微克/毫升，呈现剂量依赖性。在这些组中，出生后天数越小，半衰期越长。半衰期越长，AUC越大。Vd大于静脉滴注组，但未观察到任何特殊情况。尿液中AMK的平均峰值水平，3.0mg/kg剂量组在4至6小时为78.83微克/毫升，4.0mg/kg剂量组在2至4小时为99.17微克/毫升，6.0mg/kg剂量组在0至2小时为139.20微克/毫升。6小时内的平均尿回收率，3.0mg/kg剂量组为36.57%，4.0mg/kg剂量组为34.67%，6.0mg/kg剂量组为43.77%。这些回收率明显低于成人和儿童中观察到的回收率。回收率低的原因之一是成熟和早产婴儿的肾功能不成熟。3. 对3名早产婴儿通过30分钟静脉滴注给予3.0mg/kg的AMK时，滴注结束时血浆平均峰值水平为7.61微克/毫升。（摘要截取自400字）
