早产儿和足月新生儿生后第一周氨苄西林药代动力学。

Ampicillin Pharmacokinetics During First Week of Life in Preterm and Term Neonates.

机构信息

From the Neonatal and Pediatric Intensive Care Unit, Tartu University Hospital, Tartu, Estonia.

Department of Microbiology.

出版信息

Pediatr Infect Dis J. 2021 May 1;40(5):464-472. doi: 10.1097/INF.0000000000003061.

DOI:10.1097/INF.0000000000003061

PMID:33591074

Abstract

BACKGROUND AND AIMS

Ampicillin is 1 of the most commonly used antibiotics for treatment of early onset sepsis, but its pharmacokinetics (PK) is poorly characterized. We aimed to define the dose of ampicillin for late preterm and term neonates by evaluating its PK in serum, cerebrospinal (CSF), and epithelial lining fluid.

METHODS

A prospective study included neonates receiving ampicillin for suspected or proven early onset sepsis and pneumonia. PK samples were collected at steady state, at predose and 5 minutes, 1 hour, 3 hours, 8 hours, and 12 hours after ampicillin 3-minute infusion. Ampicillin concentrations were measured by ultra-high-performance liquid chromatography. Noncompartmental anaysis (NCA) and population pharmacokinetic (pop-PK) modeling were performed and probability of therapeutic target attainment was simulated.

RESULTS

In 14 neonates (GA of 32-42 wks; mean BW 2873 g), PK parameters (mean ± SD) in NCA were the following: half-life 7.21 ± 7.97 hours; volume of distribution (Vd) 1.07 ± 0.51 L; clearance (CL) 0.20 ± 0.13 L/h; 24-hour area under the concentration-time curve 348.92 ± 114.86 mg*h/L. In pop-PK analysis, a 2-compartmental model described the data most adequately with the final parameter estimates of CL 15.15 (CV 40.47%) L/h/70kg; central Vd 24.87 (CV 37.91%) L/70kg; intercompartmental CL 0.39 (CV 868.56) L/h and peripheral Vd 1.039 (CV 69.32%) L. Peutic target attainment simulations demonstrated that a dosage of 50 mg/kg q 12 hours attained 100% fT > MIC 0.25 mg/L, group B streptococcal breakpoint.

CONCLUSIONS

We recommend ampicillin dosage 50 mg/kg q 12 hours for neonates with gestational age ≥32 weeks during the first week of life.

摘要

背景与目的

氨苄西林是治疗早发性败血症最常用的抗生素之一，但它的药代动力学（PK）特征描述不佳。我们旨在通过评估其在血清、脑脊髓液（CSF）和上皮衬里液中的 PK 来确定早产儿和足月新生儿的氨苄西林剂量。

方法

前瞻性研究纳入了接受氨苄西林治疗疑似或确诊早发性败血症和肺炎的新生儿。在稳态时、氨苄西林输注 3 分钟后即刻、5 分钟、1 小时、3 小时、8 小时和 12 小时采集 PK 样本。通过超高效液相色谱法测量氨苄西林浓度。进行非房室分析（NCA）和群体药代动力学（pop-PK）建模，并模拟治疗目标的达标概率。

结果

在 14 名新生儿（GA 为 32-42 周；平均 BW 为 2873g）中，NCA 的 PK 参数（平均值±标准差）如下：半衰期 7.21±7.97 小时；分布容积（Vd）1.07±0.51L；清除率（CL）0.20±0.13L/h；24 小时浓度-时间曲线下面积 348.92±114.86mg*h/L。在 pop-PK 分析中，一个两室模型最能充分描述数据，最终参数估计为 CL 15.15（CV 40.47%）L/h/70kg；中央 Vd 24.87（CV 37.91%）L/70kg；隔室间 CL 0.39（CV 868.56）L/h 和外周 Vd 1.039（CV 69.32%）L。治疗目标达标模拟表明，50mg/kg q12h 的剂量可达到 100%fT>0.25mg/L，即 B 组链球菌的折点。