Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Center of Excellence for Pediatric Infectious Diseases and Vaccines, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Center of Excellence for Pediatric Infectious Diseases and Vaccines, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Int J Antimicrob Agents. 2020 Jun;55(6):105940. doi: 10.1016/j.ijantimicag.2020.105940. Epub 2020 Mar 13.
Use of colistin in children is rising in line with the increase of multidrug-resistant Gram-negative bacteria (MDR-GNB). In adults, a colistin loading dose is recommended to achieve therapeutic concentrations within 12-24 h. Here we aimed to describe the pharmacokinetic (PK) parameters of a loading dose versus a recommended initial dose of intravenous colistimethate sodium (CMS) in paediatric patients. A prospective, open-label, PK study was conducted in paediatric patients (age 2-18 years) with normal renal function. Patients (n = 20) were randomly assigned to receive either a CMS loading dose (LD group) of 4 mg of colistin base activity (CBA)/kg/dose or a standard initial dose (NLD group) of 2.5 mg (12-h interval) or 1.7 mg (8-h interval) of CBA/kg/dose. Serial blood samples were collected. Plasma concentrations of formed colistin were measured by LC-MS/MS. PK parameters were reported. Acute kidney injury (AKI) was monitored by serum creatinine and urine NGAL. The median (interquartile range) age and body weight were 8.5 (3.5-11.3) years and 21.5 (13.5-20.0) kg. The mean (standard deviation) of first-dose PK parameters of the LD group versus the NLD group were: C, 6.1 (2.4) vs. 4.1 (1.3) mg/L; AUC, 26.5 (12.5) vs. 13.5 (3.6) mg/L·h; V, 0.7 (0.4) vs. 0.6 (0.3) L/kg; and t, 2.9 (0.6) vs. 2.6 (0.4) h. No patient developed AKI by serum creatinine criteria. A CMS loading dose is beneficial for improvement of colistin exposure without increased AKI. A higher daily dose of CMS should be considered, especially for MDR-GNB treatment.
在多药耐药革兰氏阴性菌 (MDR-GNB) 增加的情况下，儿童使用黏菌素的情况也在增加。在成人中，建议使用黏菌素负荷剂量，以在 12-24 小时内达到治疗浓度。在这里，我们旨在描述黏菌素甲磺酸钠（CMS）静脉负荷剂量与推荐初始剂量在儿科患者中的药代动力学（PK）参数。在肾功能正常的儿科患者（年龄 2-18 岁）中进行了一项前瞻性、开放标签、PK 研究。患者（n=20）被随机分为接受黏菌素甲磺酸钠负荷剂量（LD 组）4 毫克黏菌素碱基活性（CBA）/kg/剂量或标准初始剂量（NLD 组）2.5 毫克（12 小时间隔）或 1.7 毫克（8 小时间隔）CBA/kg/剂量。采集连续血样。通过 LC-MS/MS 测量形成的黏菌素的血浆浓度。报告 PK 参数。通过血清肌酐和尿液 NGAL 监测急性肾损伤 (AKI)。中位（四分位间距）年龄和体重分别为 8.5（3.5-11.3）岁和 21.5（13.5-20.0）kg。LD 组与 NLD 组首剂量 PK 参数的平均值（标准差）分别为：C，6.1（2.4）比 4.1（1.3）mg/L；AUC，26.5（12.5）比 13.5（3.6）mg/L·h；V，0.7（0.4）比 0.6（0.3）L/kg；t，2.9（0.6）比 2.6（0.4）h。没有患者根据血清肌酐标准发生 AKI。黏菌素负荷剂量有利于提高黏菌素暴露水平，而不会增加 AKI。对于 MDR-GNB 治疗，应考虑使用更高的 CMS 日剂量。
