Componential Analyzer for In Vitro Pharmacokinetic Fraction Quantification
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Solution Overview
Problem
Current methods for evaluating pharmacokinetics in drug development are inadequate as they fail to provide a comprehensive picture of drug uptake, metabolism, and excretion, particularly in assessing the amount of a drug excreted to the basolateral side, which is crucial for determining efficacy and toxicity, and lack a system for quantifying fractions of a drug within cells and its distribution ratio.
Innovation Solution
A componential analyzer system with temperature-controlled containers and an analyzing unit that measures and analyzes the amount of a component excreted from cells to different buffer solutions, allowing for the quantification of fractions excreted to the basolateral side, lumen side, and retained in cells, providing a total picture of pharmacokinetics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional in vitro evaluation methods are used to assess drug excretion, then the amount of drug loss through bile ducts can be evaluated, but the amount of drug excreted to the basolateral side (which indicates efficacy) cannot be directly measured
Solution Approach 1:
The invention divides the evaluation of drug excretion into separate compartments: one for measuring biliary excretion (drug loss) and another for measuring basolateral excretion (efficacious drug). This segmentation allows simultaneous evaluation of both drug loss and efficacious drug components using the same cell culture system, resolving the contradiction between measuring total excretion and capturing efficacy information.
2Reliability
If animal experiments and human clinical trials are conducted to evaluate drug efficacy and toxicity, then comprehensive pharmacokinetic data can be obtained, but development costs increase enormously
Solution Approach 1:
The invention creates an in vitro copy of the human liver system using cultured human hepatocytes that maintain functional integrity for evaluating pharmacokinetics. This cell-based model replicates key human metabolic and excretory functions, providing reliable efficacy and toxicity data without requiring expensive animal experiments or human clinical trials, thus reducing development complexity while maintaining evaluation reliability.
3Loss of information
If a comprehensive evaluation system for total pharmacokinetics is established, then a complete picture of drug uptake, metabolism, and excretion can be obtained, but the system complexity and measurement difficulty increase
Solution Approach 1:
The invention uses a universal cell culture system that can simultaneously evaluate multiple pharmacokinetic parameters including drug uptake, metabolism, biliary excretion, and basolateral excretion. By using the same cultured human hepatocyte model for all measurements, the system provides comprehensive pharmacokinetic information without requiring multiple different assay systems, thereby reducing measurement difficulty while maintaining information completeness.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables direct evaluation of drug components excreted to the basolateral side, improving the accuracy of in vitro screening for drug candidates, reducing the need for animal experiments and unnecessary human clinical trials, and lowering development costs by identifying effective and non-toxic compounds early in the process.
Implementation Method 1
a temperature controlling unit for controlling temperature in a plurality of containers; wherein the plurality of containers includes at least a first container and a second container; the first container and the second container each contain a first buffer solution; the temperature controlling unit controls temperature in the first container and temperature in the second container so that the temperatures are different from each other
Implementation Method 2
an analyzing unit for measuring a component in the plurality of containers and analyzing the measured component; wherein the analyzing unit measures an amount of the component excreted from a cell in the first container to the first buffer solution in the first container and an amount of the component excreted from a cell in the second container to the first buffer solution in the first container
Data Source
AI summary
Application of the present invention enables quantification of fractions of candidate pharmaceutical compounds (a parent compound and its metabolites), one excreted to the basolateral (Basal/Basolateral)-side via transporters and by diffusion, one excreted to the lumen (Apical)-side, and one remained in the cells. This enables determination of the total amount of the administered candidate pharmaceutical compounds and the distribution ratio of the fractions. The kinetics of the administered candidate pharmaceutical compounds can be evaluated, thereby enabling in vitro screening of an enormous number of candidate pharmaceutical compounds for drug candidates exhibiting the efficacy. The object of the present invention is to provide an apparatus and method for understanding a total picture of pharmacokinetics in vitro by quantifying a fraction of basolateral (Basal/Basolateral) efflux, a fraction of lumen (Apical)-side excretion, and a fraction remaining in a cell of a drug which has been administered to the cell to determine the distribution ratio of each fraction.