Method for simulating the interaction of chemical compounds with live organisms

• US 20050075274A1
• Filed: 09/08/2004
• Published: 04/07/2005
• Est. Priority Date: 10/02/2003
• Status: Abandoned Application

• Current Assignee: Bayer AG
• Original Assignee: Bayer Technology Services GmbH (Bayer AG)
• Inventors: Willmann, Stefan, Fois, Franco, Schmitt, Walter
• Application Number:
  US10/936,353
• Publication Number:
  US 20050075274A1
• Time in Patent Office: Days
• US Class Current: 514/1
• CPC Class Codes: G16B 5/00 ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
• CPC Class Codes: G16B 5/30 Dynamic-time models
• CPC Class Codes: G16C 20/30 Prediction of properties of chemical compounds, compositions or mixtures
• CPC Class Codes: G16H 10/40 for data related to laboratory analysis, e.g. patient specimen analysis
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders

Abstract

A method for determining the interaction of one or more chemical active compounds with organisms. The method comprises selecting at least one compound and analyzing its physiko-chemical and/or biochemical characteristics including its pharmacokinetic properties in various anatomical and physiological compartments of the organism in question. The relevant physiological compartments are characterized with respect to the compound'"'"'s various pharmacokinetic properties that may vary with the mode of administering the compound. A combined system of coupled differential equations is then used to simulate a concentration-time curve of the active compound in selected compartments.

Claims

1. Method for determining the interaction of one or more active compounds administered to an organism, said method comprising the following steps:

A) selecting at least one compound and analyzing the compound with respect to one or more characteristics selected from the group consisting of lipophilicity, solubility, protein binding, molecular weight, molecular volume, pKa value in the case of acids or bases, metabolic degradation rate and kinetic constants of the compound'"'"'s active transporters,

B) selecting one or more anatomical and physiological compartments of the organism in question as follows;

i) in the case of mammals or insects, the selecting is from the group consisting of lungs, peripheral organs, blood vessels, arteries, veins, and blood fluid, and

ii) in the case of plants, the selecting is from the group consisting of xylem, phloem, root, leaf and stem,

C) preparing a description of one or more of the compartments in a computer program with regard to one or more transport processes selected from the group consisting of transport from and to the compartments, degradation processes, and active transport processes, and wherein the description comprises mass transport equations and kinetic reaction equations,

D) describing the transport processes and/or the degradation processes of the administered active compound in the organism by mass transport equations and kinetic reaction equations,

E) combining the equations in steps C) and D), to provide a numerical calculation of the resulting system of coupled differential equations, and

F) determining the concentration-time curve of the active compound in the selected compartments.

2. The method according to claim 1, wherein the organism(s) are selected from the group consisting of humans, monkeys, dogs, pigs, rats, mice, insects and plants.

3. The method according to claim 1, wherein the active compound is applied via a route selected from the group consisting of intravenous, oral, topical, subcutaneous, intraperitoneal, inhalative via the nose or the lungs, and intracerebrovascular in the case of mammals, or intrahaemolymphatic, topical or oral via feeding or gavage in the case of insects, or in the form of a spray mixture with foliar uptake or uptake via the roots in the case of plants.

4. The method according to claim 1, wherein the physiological parameters which describe the organisms are time-dependent parameters.

5. The method according to claim 1, wherein one or more of the parameters are taken from a database which is linked to a computer system.

6. The method according to claim 1, wherein the physiological and anatomical parameters are varied within a predetermined statistical variation by means of random numbers.

7. The method according to claim 1, wherein a computing program comprises a hierarchical model architecture consisting of modules with different functionalities, wherein at least two of the modules comprise either chemical or biological characteristics of the compound, physiological and/or anatomical information on the organism, information on the mode of the compound'"'"'s application, or the type of transport and/or metabolic process the compound is undergoing.

8. The method of claim 7, wherein an integrated model simulates drug-drug interactions in a mother-foetus model, or combined insect-plant model.

9. The method according to claim 1, wherein a multiplicity of models of organisms are combined in an integrated model.

10. The method according to claim 1, wherein the active compound is administered by a route selected from the group consisting of intravenous, peroral and subcutaneous administration.