METHOD OF DEVELOPING A PHARMACOKINETIC PROFILE OF A XENOBIOTIC DISPOSITION IN A MAMMALIAN TISSUE

• US 20080221847A1
• Filed: 03/07/2008
• Published: 09/11/2008
• Est. Priority Date: 03/09/2007
• Status: Abandoned Application

• Current Assignee: Frederique Fenetteau
• Original Assignee: Frederique Fenetteau
• Inventors: Fenetteau, Frederique
• Application Number:
  US12/044,745
• Publication Number:
  US 20080221847A1
• Time in Patent Office: Days
• US Class Current: 703/11
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/5014 for testing toxicity
• CPC Class Codes: G01N 33/5082 Supracellular entities, e.g. tissue, organisms
• CPC Class Codes: G16C 20/30 Prediction of properties of chemical compounds, compositions or mixtures

Abstract

There is provided a method of developing a pharmacokinetic profile of an xenobiotic disposition in a mammalian tissue, the method comprising inputting mammalian-specific data into a physiologically based pharmacokinetic (PBPK) model, where said mammalian-specific data comprises tansporter properties related data, where said transporter properties related data reflect genetic and environmental factors associated with said mammalian; inputting xenobiotic-specific data into said PBPK model; and simulating, using said PBPK model, a pharmacokinetic profile of said xenobiotic disposition as a function of said inputted data.

Claims

1. A method of developing a pharmacokinetic profile of an xenobiotic disposition in a mammalian tissue, the method comprising:

inputting mammalian-specific data into a physiologically based pharmacokinetic (PBPK) model, where said mammalian-specific data comprises tansporter properties related data, where said transporter properties related data reflect genetic and environmental factors associated with said mammalian;

inputting xenobiotic-specific data into said PBPK model; and

simulating, using said PBPK model, a pharmacokinetic profile of said xenobiotic disposition as a function of said inputted data.

2. The method as claimed in claim 1, wherein said transporters properties related data comprises an in vivo estimated diffusion value and at least one of an in vivo estimated efflux value and an in vivo estimated influx value of said xenobiotic through said mammalian tissue.

3. The method as claimed in claim 2, wherein said estimated in vivo diffusion value of said xenobiotic through said mammalian tissue is carried out by:

estimating an in vitro diffusion value of said xenobiotic through a membrane of said mammalian; and

using said estimated in vitro diffusion value for estimating said in vivo diffusion value of said xenobiotic through said mammalian tissue.

4. The method as claimed in claim 3, further comprising estimating a correlation value between in vitro and in vivo diffusion of said xenobiotic through said membrane, wherein said using said estimated in vitro diffusion value for estimating said in vivo diffusion value is carried out by extrapolating said estimated in vitro diffusion value using said correlation value.

5. The method as claimed in claim 4, wherein said mammalian tissue is selected from the group consisting of a heart, a brain, a liver, kidneys and intestine.

6. The method as claimed in claim 5, wherein said xenobiotic is selected from the group consisting of a drug, a herbal medicine, a chemical organic pollutant, a chemical inorganic pollutant and a cosmetic product.

7. The method as claimed in claim 6, wherein said mammalian consists of any laboratory animal or human.

8. The method as claimed in claim 7, wherein said mammalian-specific data further comprises physiological and anatomical properties of said mammalian related data.

9. The method as claimed in claim 8, wherein said physiological and anatomical properties of said mammalian related data are selected from the group consisting of volume of tissues, composition of said tissues in lipids, phospholipids and water, volume of blood in equilibrium in said tissues and blood flow to said tissues.

10. The method as claimed in claim 9, wherein said xenobiotic-specific data comprises physiochemical properties of said xenobiotic related data.

11. The method as claimed in claim 10, wherein said physiochemical properties of said xenobiotic related data are selected from the group consisting of molecular weight, lipophilicity and solubility of said xenobiotic.

12. The method as claimed in claim 11, wherein said estimating an in vitro diffusion value of said xenobiotic through a membrane of said mammalian comprises:

determining a permeability value of said xenobiotic through said membrane from apical to basolateral side;

determining a permeability value of said xenobiotic through said membrane from basolateral to apical side; and

estimating said in vitro diffusion value using said determined permeability values.

13. The method as claimed in claim 12, wherein said estimating an in vitro diffusion value is carried out by using a mathematical equation comprising as parameters said measured permeability values.

14. The method as claimed in claim 13, wherein said at least one of an in vitro estimated efflux value and an in vitro estimated influx value of said xenobiotic through said mammalian tissue is obtained by:

determining a permeability value of said xenobiotic through said membrane from apical to basolateral side;

determining a permeability value of said xenobiotic through said membrane from basolateral to apical side; and

estimating said at least one of an in vitro efflux value and an in vitro influx value using said determined permeability values.

15. The method as claimed in claim 14, wherein said estimating said at least one of an in vitro efflux value and in vitro influx value is carried out by using a mathematical equation comprising as parameters said measured permeability values.

16. The method as claimed in claim 15, wherein said estimating a correlation value between in vitro and in vivo diffusion of said xenobiotic through said membrane comprises:

estimating a correlation value between in vitro and in vivo diffusion of various transporters substrates;

estimating said correlation value between in vitro and in vivo diffusion of said xenobiotic through said membrane using said estimated correlation value between in vitro and in vivo diffusion of various transporters substrates.

17. The method as claimed in claim 16, wherein said estimations of said correlation values are carried out by using mathematical equations.

18. The method as claimed in claim 17, wherein said simulated pharmacokinetic profile of said xenobiotic disposition comprises a predicted distribution profile of said xenobiotic in said mammalian tissue.

19. The method as claimed in claim 17, wherein said simulated pharmacokinetic profile of said xenobiotic disposition comprises a predicted amount and rate of absorption of said xenobiotic in said mammalian tissue.

20. The method as claimed in claim 17, wherein said simulated pharmacokinetic profile of said xenobiotic disposition comprises a predicted concentration-time profile of said xenobiotic in said mammalian tissue.

21. The method as claimed in claim 17, wherein said simulated pharmacokinetic profile of said xenobiotic disposition comprises an eliminated amount of said xenobiotic by hepatic metabolism and by renal or fecal excretion.

22. A software code including embedded information embedded therein by the method according to claim 1.