Application of preclinical pharmacokinetic key technology and research system

Medicilon completes at least 8 IND packages and more than 1,000 individual pharmacokinetic studies every year. Email:marketing@medicilon.com.cn web:www.medicilon.com

The invention provides application of a preclinical pharmacokinetic key technology and research system in cefoperazone sodium and sulbactam sodium, comprising the steps of (1) after the cefoperazone sodium and sulbactam sodium with a certain concentration is administrated to an experimental animal for a certain time, collecting one or more biological samples in blood, urine and faeces; (2) treating the biological samples obtained in step (1) by adopting liquid-liquid extraction, albumen precipitation, and solid phase extraction technologies to obtain corresponding solutions; (3) analyzing the prepared solutions in step (2) by adopting an LC-MS(liquid chromatography-mass spectrography) and an LC-MS/MS((liquid chromatography-tandem mass spectrometry). According to the application provided by the invention, the Caco-2 cell can also be adopted to detect the membrane permeability of the medicine and cell absorptive capacity; or the medicine with a certain concentration treats primary culture cerebral microvascular endothelial cells to detect the blood-brain barrier permeability of the medicine; or by adopting a whole animal, S9, human intestinal microsome and monoclonal purified enzyme, in vitro metabolism stability of the medicine is detected and a metabolite is identified.

cefoperazone sulbactam for the treatment of susceptible bacterial infections caused by the following: respiratory tract infections (upper respiratory and lower respiratory tract), urinary tract infection (upper urinary tract and lower urinary tract), peritonitis, cholecystitis, cholangitis and other intra-abdominal infections, sepsis, meningitis, skin and soft tissue infections, eye infections, bone and joint infections, pelvic inflammatory disease, endometritis, gonorrhea and other genital tract infections; prevention because of abdominal, gynecological, cardiovascular after orthopedic surgery and plastic surgery caused infections.

is a pharmacokinetic study drug in vivo absorption, distribution, metabolism and excretion of a disciplinary procedure and the law, and pharmacodynamic study the biological activity of drugs on living organisms, respectively. Pharmacokinetic studies focus on the disposal of the body to the drug, but with the discipline development and research technology, the pharmaceutical drugs on living organisms such as transporters disposal system, the role of metabolic enzymes also belong to the pharmacokinetic scope of the study. Drug disposition in vivo properties to some extent determine its efficacy or toxicity strength, therefore, pharmacokinetic study the role and significance of a very important position in innovative drug research process.

In Europe and other developed countries, the pharmacokinetic studies on innovative drug development has run through every link, including design and optimization of lead compounds, screening and evaluation of candidate compounds, preclinical evaluation of drug candidates and clinical research . Foreign nearly two decades of experience has proved that the system of early intervention and special studies of drug metabolism moving is to improve the success rate of drug development innovation, reduce development costs and risks, accelerating the development process to achieve rational drug clinical safety key.

before the pharmacokinetics dynamics of clinical research and evaluation for a variety of technical bottlenecks, limited to research and development on the part of the late prototype drug preliminary pharmacokinetic evaluations, mainly including drug prototype plasma time course descriptive study organ distribution and the prototype drug excretion pathway. As China's new drug R & D model from the "imitation" to "imitation and integration" and "innovation-oriented" changes, our original pharmacokinetic studies evaluation system can not meet the development of new drug R & D model changing needs, can not give full play to the guiding role pharmacokinetic studies in structural design and optimization of lead compounds, new drug formulations and dosage forms designed to transform, predict drug interactions as well as clinical safety of rational drug use and the like.

Compared to Europe and other developed countries, the root causes of the existing pharmacokinetic research and development lags behind that key technical level and research system is imperfect. Quantitative analysis techniques embodied in high sensitivity of trace drugs in vivo absorption, distribution, metabolism and excretion characteristics of fast prediction, selection and evaluation techniques, pharmacokinetic - pharmacodynamic research techniques, drug interactions and forecast Related key technologies such as the lack of evaluation techniques.