A Population Pharmacokinetic Analysis for Piperacillin/Tazobactam in Patients with End-Stage Kidney Disease Undergoing Intermittent Haemodialysis: Extension of a General-Purpose Model.

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
D Kong, J V Koomen, F Vanommeslaeghe, S Delanghe, W Van Biesen, P J Colin, S Eloot
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引用次数: 0

Abstract

Background and objective: End-stage kidney disease (ESKD) patients undergoing haemodialysis (HD) require a dosing regimen that balances the low endogenous clearance with the additional dialyser clearance. This study aimed to expand a previously proposed general-purpose pharmacokinetic model for piperacillin/tazobactam with a new population of ESKD patients undergoing intermittent high-flux haemodialysis.

Methods: Inter- and intradialytic blood samples were collected in ESKD patients undergoing intermittent high-flux haemodialysis, in HD or haemodiafiltration (HDF) mode, who received piperacillin/tazobactam during routine care. The previous general-purpose model was expanded to reflect changes in the pharmacokinetics in the new patient population. A covariate search was performed focussing on factors that explained variability between patients in endogenous and dialysis clearance. Simulations were performed to determine the probability of target attainment with current dosing recommendations in this specific population.

Results: In 20 ESKD patients, 195 piperacillin/tazobactam concentrations were determined. The general-purpose model was successfully expanded, wherein endogenous piperacillin/tazobactam clearance in patients with/without residual diuresis was 63% (95% confidence interval [CI] 49.5-73.0%) and 78.6% (95% CI 66.3-86.4%) lower compared with the general population, respectively. Extraction ratios of piperacillin and tazobactam ranged from 64 to 80%. Differences in probability of target attainment (PTA) for piperacillin were observed between patients with normal kidney function and ESKD patients undergoing haemodialysis with current dosing recommendations.

Conclusion: We successfully expanded a general-purpose model to reflect the piperacillin/tazobactam pharmacokinetics in ESKD patients undergoing intermittent haemodialysis using high-flux dialysers. The current dosing recommendations provide inconsistent probability of target attainment in ESKD patients compared with the general population.

间断性血液透析终末期肾病患者哌拉西林/他唑巴坦的人群药代动力学分析:一种通用模型的扩展
背景和目的:接受血液透析(HD)的终末期肾病(ESKD)患者需要一种平衡低内源性清除率和额外透析清除率的给药方案。本研究旨在扩展先前提出的哌拉西林/他唑巴坦的通用药代动力学模型,该模型适用于接受间歇性高通量血液透析的ESKD患者。方法:对接受间歇性高通量血液透析、HD或血液滤过(HDF)模式、在常规护理中接受哌西林/他唑巴坦治疗的ESKD患者采集溶间和溶内血液样本。先前的通用模型被扩展以反映新患者群体中药代动力学的变化。进行协变量搜索,集中于解释患者内源性和透析清除率差异的因素。进行模拟以确定在这一特定人群中使用当前推荐剂量达到目标的概率。结果:20例ESKD患者共检测195例哌拉西林/他唑巴坦浓度。通用模型被成功扩展,与普通人群相比,存在/不存在残余利尿的患者的内源性哌拉西林/他唑巴坦清除率分别降低63%(95%可信区间[CI] 49.5-73.0%)和78.6% (95% CI 66.3-86.4%)。哌拉西林和他唑巴坦的提取率为64% ~ 80%。观察了正常肾功能患者和采用当前推荐剂量进行血液透析的ESKD患者哌拉西林目标达到概率(PTA)的差异。结论:我们成功地扩展了一个通用模型,以反映使用高通量透析器进行间歇性血液透析的ESKD患者哌拉西林/他唑巴坦的药代动力学。与一般人群相比,目前的剂量建议在ESKD患者中提供了不一致的目标实现概率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.80
自引率
4.40%
发文量
86
审稿时长
6-12 weeks
期刊介绍: Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics. Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.
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