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基于模型的替考拉宁剂量优化及治疗药物监测在复杂或非复杂耐甲氧西林金黄色葡萄球菌感染患者中的应用。

Model-based dosing optimization and therapeutic drug monitoring practices of teicoplanin in patients with complicated or non-complicated methicillin-resistant staphylococcus aureus infection.

机构信息

Department of Pharmacy, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

School of Pharmacy, Wenzhou Medical University, Wenzhou, China.

出版信息

Br J Clin Pharmacol. 2024 Feb;90(2):452-462. doi: 10.1111/bcp.15912. Epub 2023 Oct 21.

Abstract

AIMS

This study aims to establish a population pharmacokinetic (PK) model of teicoplanin in Chinese adult patients to evaluate the dosing regimen in the label sheet and optimize it.

METHODS

Nonlinear mixed-effects modelling was used to estimate PK parameters. Monte Carlo simulations were used to evaluate the attainment of various dosing regimens in achieving the target trough concentrations in patients with normal or decreased renal function.

RESULTS

A total of 115 patients were enrolled in this retrospective study. Creatinine clearance (CrCL) and albumin (ALB) were identified as covariates on the clearance of teicoplanin. For the treatment of non-complicated methicillin-resistant Staphylococcus aureus (MRSA) infections in patients with normal renal function and serum ALB concentration, the recommended dosing regimen was 600 mg q12h with five administrations as the loading dose followed by 600 mg qd as the maintenance dose; for the treatment of serious and/or complicated MRSA infections, the recommended dosing regimen was 800 mg q12h with five administrations as the loading dose followed by 800 mg qd as the maintenance dose. It is worth noting that both the loading and maintenance doses ought to be modified based on the patient's renal function and serum ALB concentration. In addition, trough concentrations of teicoplanin were significantly increased every other week.

CONCLUSIONS

Both loading dosing and maintenance dosing regimens were recommended to be adjusted according to patient's renal function and serum ALB concentration. In addition, it is necessary to perform follow-up therapeutic drug monitoring of teicoplanin at least once every week.

摘要

目的

本研究旨在建立替考拉宁在中国成年患者中的群体药代动力学(PK)模型,以评估标签说明书中的给药方案并对其进行优化。

方法

采用非线性混合效应模型估算 PK 参数。采用蒙特卡罗模拟评估不同给药方案在实现肾功能正常或降低的患者目标谷浓度方面的达标情况。

结果

本回顾性研究共纳入 115 例患者。发现肌酐清除率(CrCL)和白蛋白(ALB)是替考拉宁清除率的协变量。对于肾功能正常且血清 ALB 浓度正常的非复杂性耐甲氧西林金黄色葡萄球菌(MRSA)感染患者,推荐的给药方案为 600mg,q12h,5 次负荷剂量后 600mg,qd 维持剂量;对于严重和/或复杂性 MRSA 感染,推荐的给药方案为 800mg,q12h,5 次负荷剂量后 800mg,qd 维持剂量。值得注意的是,无论是负荷剂量还是维持剂量,都应根据患者的肾功能和血清 ALB 浓度进行调整。此外,替考拉宁的谷浓度每两周显著增加。

结论

建议根据患者的肾功能和血清 ALB 浓度调整负荷剂量和维持剂量方案。此外,有必要每周至少进行一次替考拉宁的治疗药物监测随访。

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