Petersen P O, Wells T G, Kearns G L
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock.
Dev Pharmacol Ther. 1991;16(4):203-11.
A dosing chart for amikacin (AMK) was developed from average pharmacokinetic parameters for infants with varying postnatal ages and birth weights ranging from less than 800 to greater than 2,500 g. This chart was then evaluated in 38 infants (648-5,404 g; 25-43 weeks postconceptional age, estimated glomerular filtration rate (GFR) 9.0-49.0 ml/min/1.73 m2) with suspected infection by comparison of predicted versus observed steady-state peak (Cssmax) and trough (Cssmin) serum AMK concentrations. Additionally, the apparent elimination half-life (t1/2) for AMK was determined for each infant using two postinfusion serum concentrations obtained at steady state. As expected, linear correlations were found between the elimination rate constant (Ke) for AMK and both postconceptional age (PCA; y = -0.54 + 0.005x; r = 0.59, p less than 0.01) and estimated GFR (y = 0.05 + 0.002x; r = 0.65; p less than 0.01). The dosing chart produced desired therapeutic Cssmax values (e.g. 20-30 micrograms/ml) in 76.3% of patients, with 2.6 and 21.1% having values less than 20 and greater than 30 micrograms/ml, respectively. Desired therapeutic Cssmin serum AMK concentrations (e.g. 4-10 micrograms/ml) were obtained in 71.1% of patients, with 10.5 and 18.4% having concentrations of less than 4 and greater than 10 micrograms/ml, respectively. However, significant linear correlations were not found between the predicted versus observed values for either Cssmax or Cssmin. The AMK dosing chart for neonates enables attainment of desired therapeutic serum concentrations in the majority of infants at the initiation of therapy despite wide variability in PCA, birth weights and estimated GFR.
根据不同出生后年龄和出生体重（800克以下至2500克以上）婴儿的平均药代动力学参数制定了阿米卡星（AMK）给药图表。然后，在38例疑似感染的婴儿（体重648 - 5404克；孕龄25 - 43周，估计肾小球滤过率（GFR）9.0 - 49.0毫升/分钟/1.73平方米）中，通过比较预测的与观察到的稳态峰浓度（Cssmax）和谷浓度（Cssmin）血清AMK浓度对该图表进行评估。此外，使用在稳态时获得的两次输注后血清浓度为每个婴儿测定AMK的表观消除半衰期（t1/2）。正如预期的那样，发现AMK的消除速率常数（Ke）与孕龄（PCA；y = -0.54 + 0.005x；r = 0.59，p小于0.01）和估计的GFR（y = 0.05 + 0.002x；r = 0.65；p小于0.01）之间存在线性相关性。该给药图表在76.3%的患者中产生了所需的治疗性Cssmax值（例如20 - 30微克/毫升），分别有2.6%和21.1%的患者其值低于20微克/毫升和高于30微克/毫升。71.1%的患者获得了所需的治疗性Cssmin血清AMK浓度（例如4 - 10微克/毫升），分别有10.5%和18.4%的患者其浓度低于4微克/毫升和高于1微克/毫升。然而，未发现Cssmax或Cssmin的预测值与观察值之间存在显著的线性相关性。尽管PCA、出生体重和估计的GFR存在很大差异，但新生儿AMK给药图表能够在大多数婴儿治疗开始时达到所需的治疗性血清浓度。
