Background

The pharmacokinetics of vancomycin, a drug used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA), varies between paediatric and adult patients.

Objective

The objective of this study was to assess the pharmacokinetics of vancomycin in preterm neonates and determine the optimum dose regimen.

Methods

This was a randomised double-blind study of preterm neonates admitted to neonatal intensive care units. They all received vancomycin 15 mg/kg every 12 h. Blood was sampled just before administration of the third, sixth and ninth vancomycin dose. Pharmacokinetic parameters were estimated using a Bayesian approach implemented in Monolix 2018R2 software. Covariates assessed included postmenstrual age, current weight, creatinine clearance, albumin, gestational age, body surface area and current age. We used Monte Carlo simulations for dose regimen optimisation targeting area under the concentration–time curve up to 24 h (AUC_0–24h) of ≥ 400 mg × h/L.

Results

In total, 19 preterm neonates were enrolled in the study with a median age of 14 (3–58) days. A one-compartment model with linear elimination best described the pharmacokinetics of vancomycin. Volume of distribution and clearance was 0.88 L and 0.1 L/h, respectively, for a typical neonate weighing 1.48 kg. Simulation of the current dose regimen showed that 27.5% of the neonates would achieve the target AUC_0–24h of ≥ 400 mg × h/L, and 70.7% of the neonates would achieve it with 12 mg/kg every 8 h.

Conclusion

The majority of the neonates were under dosed. Vancomycin 12 mg/kg should be administered every 8 h over 1 h infusion to improve the likelihood of achieving the AUC_0–24h target of ≥ 400 mg × h/L. This target is considered optimal for MRSA infections, where the vancomycin minimum inhibitory concentration is ≤ 1 µg/mL.

中文翻译：

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万古霉素药代动力学评估和早产儿剂量方案优化。

背景

万古霉素（一种用于治疗耐甲氧西林的金黄色葡萄球菌（MRSA）的药物）的药代动力学在儿童和成人患者之间有所不同。

目的

这项研究的目的是评估万古霉素在早产儿中的药代动力学，并确定最佳剂量方案。

方法

这是一项对进入新生儿重症监护室的早产儿进行的随机双盲研究。他们每12小时都接受15 mg / kg万古霉素。在服用第三，第六和第九万古霉素之前就取样了血液。使用在Monolix 2018R2软件中实现的贝叶斯方法估算药代动力学参数。评估的协变量包括月经后年龄，当前体重，肌酐清除率，白蛋白，胎龄，体表面积和当前年龄。我们在浓度-时间曲线下长达24 h（AUC _0-24h）_≥400 mg×h / L的剂量方案优化目标区域使用了Monte Carlo模拟。

结果

本研究共纳入19名早产儿，中位年龄为14（3-58）天。具有线性消除的一室模型最能说明万古霉素的药代动力学。对于重达1.48 kg的典型新生儿，分布和清除的体积分别为0.88 L和0.1 L / h。当前剂量方案的模拟显示，27.5％的新生儿将达到目标AUC _0-24h≥400 mg×h / L，而70.7％的新生儿每8小时可达到12 mg / kg。

结论

大多数新生儿剂量不足。输注1小时后每8小时应给予万古霉素12 mg / kg，以提高实现AUC _{0–24h≥400} mg×h / L的可能性。该目标被认为是MRSA感染的最佳选择，其中万古霉素的最低抑制浓度≤1 µg / mL。