Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas Department of Medicine, University of Cape Town, Observatory, South Africa.
Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
Clin Infect Dis. 2015 Aug 15;61 Suppl 1:S18-24. doi: 10.1093/cid/civ426.
The hollow fiber system model of tuberculosis (HFS-TB) is designed to perform pharmacokinetics/pharmacodynamics (PK/PD) experiments, and hence the design of optimal doses and dose schedules for the treatment of tuberculosis. To determine if this model is useful for deriving PK/PD data relevant to clinical outcomes, we compared its quantitative output to that from clinical trials.
We performed a PubMed search to identify clinical studies performed with antituberculosis therapy in which PK/PD data and/or parameters were documented or a dose-scheduling study design was employed. The search period was from January 1943 to December 2012. All clinical studies were published prior to HFS-TB experiments. Bias minimization was done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Clinical publications were scored for quality of evidence, with 1 as the highest score (randomized controlled trials or meta-analyses of such studies), and 4 as the lowest score.
We identified 17 studies that examined the same parameters as in 8 HFS-TB studies. Fifteen of 17 studies had a quality-of-evidence score of 1. The sterilizing and bactericidal effect rates for isoniazid, rifampin, pyrazinamide, and ethambutol were the same in the HFS-TB as in patients. Time to emergence of resistance for monotherapy was the same as in patients. The PK/PD indices associated with efficacy were the same in HFS-TB as in patients for all drugs examined.
The HFS-TB model is highly accurate at identifying optimal drug exposures, doses, and dosing schedules for use in the clinic.
结核中空纤维系统模型（HFS-TB）旨在进行药代动力学/药效学（PK/PD）实验，从而设计治疗结核病的最佳剂量和剂量方案。为了确定该模型是否可用于获得与临床结果相关的 PK/PD 数据，我们将其定量结果与临床试验进行了比较。
我们进行了 PubMed 检索，以确定使用抗结核治疗进行的临床研究，其中记录了 PK/PD 数据和/或参数，或采用了剂量方案设计。检索期为 1943 年 1 月至 2012 年 12 月。所有临床研究均在 HFS-TB 实验之前发表。根据系统评价和荟萃分析的首选报告项目进行了偏差最小化。对临床出版物的证据质量进行评分，最高得分为 1（随机对照试验或此类研究的荟萃分析），最低得分为 4。
我们确定了 17 项研究，这些研究检查了与 8 项 HFS-TB 研究相同的参数。17 项研究中有 15 项的证据质量评分为 1。异烟肼、利福平、吡嗪酰胺和乙胺丁醇的杀菌和杀菌效果在 HFS-TB 与患者中相同。单药治疗出现耐药的时间与患者相同。在所有检查的药物中，与疗效相关的 PK/PD 指标在 HFS-TB 与患者中相同。
HFS-TB 模型非常准确地确定了在临床中使用的最佳药物暴露、剂量和给药方案。
