Zenk K E, Miwa L, Cohen J L, Waffarn F, Huxtable R F
Clin Pharm. 1984 Mar-Apr;3(2):170-3.
The pharmacokinetics of gentamicin in large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) newborn infants were compared in a prospective study. Serum gentamicin concentrations were drawn just before (trough) or after (peak) the third or fourth dose of gentamicin sulfate 2.5 mg/kg given as a 30-minute i.v. infusion every 12 hours to 11 LGA and 12 AGA infants. Peak (Cmax) and trough ( Cmin ) serum concentrations, elimination rate constants (k), volumes of distribution (V), and clearances (CL) were compared between the AGA and LGA groups and within the LGA group between obese (n = 6) and nonobese (n = 5) infants. The serum gentamicin concentrations achieved in the LGA infants were similar to those in the AGA infants, with Cmin values less than 2 micrograms/ml and Cmax values of 4-7 micrograms/ml. The mean pharmacokinetic variables determined were consistent with literature values reported for AGA infants. No significant differences in these variables were observed between the two groups or within the LGA group. Greater variability in Cmax, V, and CL was observed in the LGA group as a whole. The initial dose of gentamicin now recommended for AGA infants should be appropriate for LGA infants. However, serum concentrations should be monitored carefully to detect interindividual variability in pharmacokinetics so that adjustments can be made to ensure therapeutic serum concentrations.
在一项前瞻性研究中，比较了大于胎龄（LGA）和适于胎龄（AGA）新生儿中庆大霉素的药代动力学。对11名LGA婴儿和12名AGA婴儿每12小时静脉输注2.5mg/kg硫酸庆大霉素30分钟，在第三次或第四次给药前（谷浓度）或给药后（峰浓度）采集血清庆大霉素浓度。比较了AGA组和LGA组之间以及LGA组内肥胖（n = 6）和非肥胖（n = 5）婴儿的峰浓度（Cmax）、谷浓度（Cmin）、消除速率常数（k）、分布容积（V）和清除率（CL）。LGA婴儿达到的血清庆大霉素浓度与AGA婴儿相似，Cmin值小于2μg/ml，Cmax值为4 - 7μg/ml。所测定的平均药代动力学变量与报道的AGA婴儿的文献值一致。两组之间或LGA组内这些变量均未观察到显著差异。整体上LGA组中Cmax、V和CL的变异性更大。目前推荐给AGA婴儿的庆大霉素初始剂量应适用于LGA婴儿。然而，应仔细监测血清浓度以检测药代动力学的个体间变异性，以便进行调整以确保治疗性血清浓度。
