Method for constructing pharmacokinetic-pharmacodynamic (PK/PD) synchronization model of cefquinome and application thereof

Abstract

The invention discloses a method for constructing a pharmacokinetic-pharmacodynamic (PK / PD) synchronization model of cefquinome and application thereof. The method specifically includes: detecting thedrug sensitivity of the antibacterial drug to the corresponding bacterial microorganism, and obtaining the MIC distribution range; using liquid chromatography detection method to determine the free drug concentration in the plasma samples obtained at different time points after administration of healthy and disease model animals to obtain a drug time curve; fitting the pharmacokinetic parametersof the drug by pharmacokinetic software to obtain PK parameters; studying, the antibacterial effect of antibacterial drugs on pathogenic bacteria under in vitro and semi-in vivo conditions, and obtaining PD parameters after fitting; establishing the semi-in vivo PK-PD model according to the Sigmoid Emax equation; and based on this model, using the dose calculation method and Mlxplore software to formulate different dosage regimen under the purpose of the medicine. The invention has guiding significance for the clinical application of cefquinome.

Description

technical field [0001] The invention belongs to the field of clinical medicine, and in particular relates to a method for constructing a cefquinome pharmacokinetic-drug effect synchronous model and an application thereof. Background technique [0002] In recent years, due to the irregular use and abuse of antibacterial drugs, the rapid emergence and spread of bacterial resistance has led to the gradual increase in the resistance of many bacteria, and the rate of drug resistance is also increasing. Even as high as 100%, the current clinical use of antibacterial drugs urgently needs to be scientifically and rationally regulated to slow down the emergence and spread of bacterial resistance. [0003] The pharmacokinetic-pharmacodynamic (PK / PD) combination model reflects the relationship between the in vivo process of the drug, the effect of the drug on the body, and the changes over time. Applying the PK / PD combination model to the formulation and optimization of clinical antim...

AI Technical Summary

Problems solved by technology

[0004] So far, there have been many reports on the research on the PK / PD binding model of antibacterial drugs, but many research contents have the following problems: (1) It only stays on the absorption, distribution, metabolism and elimination of antibacterial drugs in the body, ignoring the PK / PD binding model The causal relationship between antimicrobial drug administration regimen and therapeutic effect; (2) The focus tissue or organ is not targeted, and there are certain errors in the research method

It has been reported that the pharmacokinetic parameters of antibacterial drugs in porcine alveolar fluid are obtained by slaughtering experimental animals at designated locations and taking lung tissue for pre-grinding. The drug concentration does not represent the real drug concentration in the lungs, and there is a large error with the real result

Images