Kim Yong-Kyun, Jo Kyeong-Min, Lee Jae-Ha, Jang Ji-Hoon, Choe Eun-Jun, Kang Gaeun, Zang Dae-Young, Lee Dong-Hwan
Division of Infectious Diseases, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14066, Republic of Korea.
Department of Infectious Diseases, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, Republic of Korea.
Pharmaceutics. 2024 Apr 5;16(4):499. doi: 10.3390/pharmaceutics16040499.
In patients with normal renal function, significant teicoplanin dose adjustments are often necessary. This study aimed to develop a population pharmacokinetic (PK) model for teicoplanin in healthy adults and use it to recommend optimal dosage regimens for patients with normal renal function. PK samples were obtained from 12 subjects and analyzed using a population approach. The derived parameters informed Monte Carlo simulations for dosing recommendations. The PK profile was best described using a three-compartment model, in which the estimated glomerular filtration rate calculated via the CKD-EPI equation and adjusted for body surface area was identified as a significant covariate affecting total clearance. For pathogens with a minimum inhibitory concentration of 1 mg/L, a loading dose (LD) of 14 mg/kg administered every 12 h for four doses, followed by a maintenance dose (MD) of 16 mg/kg administered every 24 h, is recommended. These findings indicate the need for dosage adjustments, such as increasing the LD and MD or decreasing the dosing interval of MD in patients with normal renal function. Because of the long half-life of teicoplanin and the requirement for long-term administration, therapeutic drug monitoring at strategic intervals is important to avoid nephrotoxicity associated with elevated trough concentrations.
在肾功能正常的患者中,替考拉宁剂量通常需要进行显著调整。本研究旨在建立健康成年人替考拉宁的群体药代动力学(PK)模型,并利用该模型为肾功能正常的患者推荐最佳给药方案。从12名受试者获取PK样本,并采用群体方法进行分析。推导得到的参数为剂量推荐的蒙特卡洛模拟提供依据。PK曲线用三室模型能得到最佳描述,其中通过CKD-EPI方程计算并根据体表面积进行调整的估计肾小球滤过率被确定为影响总清除率的显著协变量。对于最低抑菌浓度为1 mg/L的病原体,推荐给予负荷剂量(LD),即每12小时给予14 mg/kg,共4剂,随后给予维持剂量(MD),即每24小时给予16 mg/kg。这些研究结果表明,肾功能正常的患者需要进行剂量调整,如增加LD和MD或缩短MD的给药间隔。由于替考拉宁半衰期长且需要长期给药,定期进行治疗药物监测对于避免与谷浓度升高相关的肾毒性很重要。