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首页> 外文期刊>The Journal of Antibiotics: An International Journal >PK-PD modeling of beta-lactam antibiotics: in vitro or in vivo models?
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PK-PD modeling of beta-lactam antibiotics: in vitro or in vivo models?

机译：β-内酰胺类抗生素的PK-PD建模：体外还是体内模型？

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摘要

A modified E(max)-pharmacokinetic-pharmacodynamic (PK-PD) model was previously proposed in literature for describing the antimicrobial activity of beta-lactam antibiotics based on in vitro experiments. However, bacteria behave differently in vitro and in vivo. Thus, the aims of this study were to model the killing effect of piperacillin (PIP) against Escherichia coli on immunocompromised infected rats using this model and to compare the parameters obtained in vitro and in vivo for the same bacteria/drug combination. The PK-PD parameters determined in vitro and in vivo were as follows: generation rate constant of 1.30 +/- 0.10 and 0.76 +/- 0.20 h(-1), maximum killing effect of 3.11 +/- 0.27 and 1.38 +/- 0.20 h(-1) and concentration to produce 50% of the maximum effect of 5.44 +/- 0.03 and 1.31 +/- 0.27 mug ml(-1), respectively. The comparison between the in vitro and in vivo parameters was not straightforward and had to take into consideration the intrinsic differences of the models involved. So far, the main application of the PK-PD model evaluated is for the comparison of different antimicrobial agent's potency and efficacy, under equivalent conditions.
机译：先前在文献中提出了一种改良的E（max）-药代动力学-药效学（PK-PD）模型，用于描述基于体外实验的β-内酰胺类抗生素的抗菌活性。但是，细菌在体外和体内的行为不同。因此，本研究的目的是使用该模型来模拟哌拉西林（PIP）对大肠杆菌对免疫受损的大鼠的杀伤作用，并比较在体外和体内获得的相同细菌/药物组合的参数。体外和体内测定的PK-PD参数如下：产生速率常数为1.30 +/- 0.10和0.76 +/- 0.20 h（-1），最大杀伤作用为3.11 +/- 0.27和1.38 +/- 0.20 h（-1）和浓度分别产生5.44 +/- 0.03和1.31 +/- 0.27毫升ml（-1）的最大效果的50％。体外和体内参数之间的比较并不直接，必须考虑所涉及模型的内在差异。到目前为止，所评估的PK-PD模型的主要应用是在等效条件下比较不同抗菌剂的效价和功效。

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