Announcement of Basic Pharmacokinetics Course

Basics of ADME

This lecture will provide an overview of Absorption, Distribution, Metabolism, and Excretion, which are the processes by which administered drugs show efficacy and disappear. The ADME of antibody drugs, which are protein drugs, will also be explained in terms of the differences from that of small molecule drugs.

Basics of Pharmacokinetic Analysis – A Story about AUC

In basic research and safety evaluation studies for drug discovery, flat cell culture systems using flasks and the like have been commonly used. In recent years, engineering technologies have been developed to make such conventional culture systems more similar to living organisms, and the culture systems constructed by such technologies are called “microphysiological systems (MPS)”. In this lecture, I would like to introduce the fundamentals of MPS, such as the method of preparation and its advantages and disadvantages, examples of its application to drug discovery, and our recently developed human placental MPS as an example of our efforts toward the practical application of MPS.

Biodistribution of gene therapeutic products and its regulation

Gene therapeutic products are being developed as a new modality and used to treat diseases. The ICHS12 guideline, “Concept of Non-clinical Biodistribution of Gene Therapy Products,” provides points to consider regarding the interpretation of data and indications. In this presentation, the biodistribution of recombinant viral vectors, an in vivo gene therapy product, will be introduced as an example, including the evaluation of quantitative methods in biological samples and their criteria.

Basics of PBPK Model Analysis

In recent years, physiological drug kinetics (PBPK) models commonly used in drug development treat blood and tissues as compartments and express the movement of drugs between them using mathematical equations. By incorporating physiological information such as blood flow velocity and enzyme activity, it is possible to simulate pharmacokinetic changes associated with pathological conditions and drug-drug interactions. In this presentation, the basics of PBPK model analysis will be outlined along with some simple examples of analysis.

In the simplified physiologically-based pharmacokinetic model, the absorption rate constant _ka, volume of distribution _V1, hepatic _intrinsic clearance CLh_,int, etc. are input in addition to substance-specific descriptors such as fat-soluble logP to reproduce or predict pharmacokinetics in the body. We collected blood concentration trend values for more than 350 chemical substances in rats and humans. Using the above reproduced kinetic parameter values as original data, we established a machine learning system to calculate kinetic parameter values, and introduced a method to predict the exposure of substances without blood concentration information after virtual oral administration.

Analysis of Drug Concentrations in Biological Samples: Analytical Principles of Two Major Methods and Examples of Compliance with International Harmonization

Analysis of drug concentrations in biological samples is a fundamental technology for accurately quantifying drugs and their metabolites and visualizing their pharmacokinetics in the body. Currently, chromatographic methods using LC-MS and ligand binding methods based on antigen-antibody reactions have been established as analytical methods for drug concentration in biological samples. In this lecture, the analytical principles of these two methods will be explained and examples of how companies are responding to the International Harmonization Guideline (ICH M10), which came into effect last year, will be introduced.