Department of Pharmacology & Therapeutics, College of Medicine & Medical Sciences, Arabian Gulf University, Manama, Bahrain.
Department of Pediatrics, College of Medicine & Medical Sciences, Arabian Gulf University, Manama, Bahrain.
Curr Drug Metab. 2020;21(4):270-280. doi: 10.2174/1389200221666200512111131.
Appropriate dosing of gentamicin in critically ill neonates is still debated.
To assess the peak concentration (Cmax) and area-under-the-time-concentration curve (AUC0-24) of gentamicin and to simulate the recommended doses using the Monte Carlo method.
This was a retrospective study on critically ill neonates carried over a one-year period. The demographic characteristics, dosage regimen and gentamicin concentrations were recorded for each neonate. Using Bayesian pharmacokinetic modeling, Cmax and AUC0-24 were predicted. Dose recommendations for the target Cmax (μg/ml) of 12 were obtained, and Monte Carlo simulation (100,000 iterations) was used for predicting the pharmacokinetic parameters and recommended doses for various birth weight categories.
Eighty-two critically ill neonates (with an average gestational age of 33.7 weeks; and birth weight of 2.1 kg) were recruited. Higher Cmax and AUC0-24 values were predicted in premature neonates, with greater cumulative AUCs in extremely preterm neonates. The average administered dose was 4 mg/kg/day and 75% of the participants had Cmax greater than 12 μg/ml following a single dose, and 85% were found to be at steady state. On the contrary, only 25% of the study population had the recommended AUC0-24 (above 125 μg-hr/ml). Simulation tests indicate that 90% of the critically ill neonates would achieve recommended Cmax with doses ranging between 5 and 6 mg/kg/day.
Currently used dose of 4 mg/kg/day is adequate to maintain Cmax in a large majority of the study population, with one-fourth population reporting the recommended AUC0-24. Increasing the dose to 5-6 mg/kg/day will more likely help to achieve both the recommended Cmax and AUC0-24 values.
在危重新生儿中，庆大霉素的适当剂量仍存在争议。
评估庆大霉素的峰浓度（Cmax）和时间浓度曲线下面积（AUC0-24），并使用蒙特卡罗法模拟推荐剂量。
这是一项为期一年的危重新生儿回顾性研究。记录每位新生儿的人口统计学特征、剂量方案和庆大霉素浓度。使用贝叶斯药代动力学模型预测 Cmax 和 AUC0-24。获得目标 Cmax（μg/ml）为 12 的剂量推荐，并使用蒙特卡罗模拟（100,000 次迭代）预测不同出生体重类别下的药代动力学参数和推荐剂量。
共纳入 82 例危重新生儿（平均胎龄 33.7 周，出生体重 2.1kg）。早产儿的 Cmax 和 AUC0-24 值预测值较高，极早产儿的累积 AUC 更大。平均给药剂量为 4mg/kg/天，单次给药后 75%的参与者 Cmax 大于 12μg/ml，85%的参与者达到稳态。相反，只有 25%的研究人群的 AUC0-24 达到推荐值（大于 125μg-hr/ml）。模拟试验表明，90%的危重新生儿在 5-6mg/kg/天的剂量范围内可达到推荐的 Cmax。
目前使用的 4mg/kg/天剂量可维持大多数研究人群的 Cmax，四分之一的人群报告 AUC0-24 达到推荐值。增加剂量至 5-6mg/kg/天可能更有助于达到推荐的 Cmax 和 AUC0-24 值。
