A combined in vivo pharmacokinetic-in vitro pharmacodynamic approach to simulate target site pharmacodynamics of antibiotics in humans

药代动力学 体内 药效学 药理学 环丙沙星 微透析 抗生素 体外 抗菌剂 化学 医学 生物 微生物学 生物化学 生物技术
作者
Simon Delacher,Hartmut Derendorf,Ursula Hollenstein,Markus Brunner,Christian Joukhadar,Silke Hofmann,Apostolos P. Georgopoulos,H.-G. Eichler,Markus Müller
出处
期刊:Journal of Antimicrobial Chemotherapy [Oxford University Press]
卷期号:46 (5): 733-739 被引量:77
标识
DOI:10.1093/jac/46.5.733
摘要

We describe a new approach to quantify in vivo anti-infective activity by simulating effect site pharmacokinetics of antibiotics in vitro. This approach is based on (i) the in vivo measurement of interstitial drug pharmacokinetics (PK) at the target site and (ii) a subsequent pharmacodynamic (PD) simulation of the time versus drug concentration profile in an in vitro setting. To demonstrate the feasibility of this approach, individual time-concentration profiles of ciprofloxacin were measured in the interstitial space fluid of eight healthy volunteers by microdialysis following iv administration of 200 mg. Thereafter, different isolates of Pseudomonas aeruginosa were exposed in vitro to the interstitial ciprofloxacin concentration profile obtained from in vivo experiments. This led to a 1- to 3-log10 decrease in the number of viable organisms after 8 h. Significant correlations were observed between the maximal bactericidal effect and several PK surrogate parameters, notably the AUC/MIC ratio (P: = 0.0005), the C:max/MIC ratio (P: = 0.006) and the time > MIC (P: = 0.02). Furthermore, the data were analysed with an integrated PK-PD model allowing a much more detailed evaluation of the data than using MIC. The model employed an E:max relationship to link unbound ciprofloxacin concentration to bacterial kill rate. In conclusion, our experiments show that therapeutic success and failure in antimicrobial therapy may be explained by pharmacokinetic variability at the target site. Therefore, the in vivo PK-in vitro PD approach presented in our study may provide valuable guidance for drug and dose selection of antimicrobial agents.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
科研通AI2S应助罗小小采纳,获得10
2秒前
GGDA完成签到 ,获得积分10
3秒前
4秒前
你的男孩广坤完成签到,获得积分10
4秒前
6秒前
starofjlu应助Foremelon采纳,获得10
7秒前
科研通AI2S应助文文采纳,获得10
8秒前
8秒前
8秒前
haku发布了新的文献求助20
8秒前
白菜兔子完成签到 ,获得积分10
10秒前
JamesPei应助滕达采纳,获得10
10秒前
11秒前
11秒前
Dxy-TOFA发布了新的文献求助10
11秒前
12秒前
LHW完成签到,获得积分10
12秒前
Guoyeye完成签到,获得积分10
13秒前
怪味基德发布了新的文献求助10
13秒前
NexusExplorer应助科研通管家采纳,获得10
14秒前
搜集达人应助科研通管家采纳,获得10
14秒前
14秒前
研友_VZG7GZ应助科研通管家采纳,获得10
14秒前
14秒前
15秒前
16秒前
17秒前
18秒前
Ava应助Aic采纳,获得10
18秒前
18秒前
sdkabdrxt完成签到,获得积分10
19秒前
沈泊安完成签到,获得积分10
20秒前
滕达发布了新的文献求助10
22秒前
无限雨南发布了新的文献求助10
23秒前
123发布了新的文献求助10
26秒前
26秒前
小卡啦完成签到 ,获得积分10
26秒前
27秒前
29秒前
高分求助中
Evolution 10000
Sustainability in Tides Chemistry 2800
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
юрские динозавры восточного забайкалья 800
Diagnostic immunohistochemistry : theranostic and genomic applications 6th Edition 500
Chen Hansheng: China’s Last Romantic Revolutionary 500
China's Relations With Japan 1945-83: The Role of Liao Chengzhi 400
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3149289
求助须知:如何正确求助?哪些是违规求助? 2800391
关于积分的说明 7839862
捐赠科研通 2457980
什么是DOI,文献DOI怎么找? 1308158
科研通“疑难数据库(出版商)”最低求助积分说明 628456
版权声明 601706