Predicting pharmacokinetic and pharmacodynamic responses

• US 10,013,515 B2
• Filed: 09/01/2016
• Issued: 07/03/2018
• Est. Priority Date: 12/17/2012
• Status: Active Grant

• Current Assignee: Arrapoi, Inc.
• Original Assignee: Arrapoi, Inc.
• Inventors: Williams, Glenn A.
• Primary Examiner(s): VINCENT, DAVID ROBERT
• Application Number:
  US15/254,514
• Publication Number:
  US 20170032066A1
• Time in Patent Office: 670 Days
• Field of Search: 706 15, 706 45
• CPC Class Codes: G06F 17/17 Function evaluation by approximation methods, e.g. inter- or extrapolation, smoothing, least mean square method G06F17/18 takes precedence ; interpolation for numerical control G05B19/18
• CPC Class Codes: G06F 2111/10 Numerical modelling
• CPC Class Codes: G06F 30/20 Design optimisation, verification or simulation optimisation, verification or simulation of circuit designs G06F30/30
• CPC Class Codes: G06N 5/02 Knowledge representation; Symbolic representation
• 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: G16C 20/30 Prediction of properties of chemical compounds, compositions or mixtures

Abstract

Non-mechanistic, differential-equation-free approaches for predicting a particular pharmacokinetic and pharmacodynamic responses of a system to a given input are provided in the form of systems, methods, and devices. These approaches are generally directed to a non-compartmental method of predicting a time-dependent pharmacokinetic response, or pharmacodynamics response, of a component of a system to an input into the system. The systems, methods, and devices provide the ability to (i) reduce the cost of research and development by offering an accurate modeling of heterogeneous and complex physical systems; (ii) reduce the cost of creating such systems and methods by simplifying the modeling process; (iii) accurately capture and model inherent nonlinearities in cases where sufficient knowledge does not exist to a priori build a model and its parameters; and, (iv) provide one-to-one relationships between model parameters and model outputs, addressing the problem of the ambiguities inherent in the current, state-of-the-art systems and methods.

Claims

1. A non-compartmental method of predicting a time-dependent, pharmacokinetic response of a component of a mammalian system to an input into the system, the method comprising:

selecting a component of the system, the component selected from the group consisting of a body fluid;

selecting a set of actual inputs, the set of actual inputs having an element selected from the group consisting of a DNA, a virus, a protein, an antibody, a bacteria, a chemical, a dietary supplement, a nutrient, and a drug;

obtaining a set of time-dependent actual pharmacokinetic responses of the component to the set of actual inputs;

using the set of actual inputs and the set of time-dependent actual pharmacokinetic responses to provide a model for predicting a test pharmacokinetic response to a test input, the model comprising the formula

2. The method of claim 1, wherein the component is blood, blood plasma, or blood serum.

3. The method of claim 1, wherein the component is urine.

4. The method of claim 1, wherein the component saliva.

5. The method of claim 1, wherein the test pharmacokinetic response is a bacterial load.

6. The method of claim 1, wherein the test pharmacokinetic response is a viral load.

7. The method of claim 1, wherein the test pharmacokinetic response is a drug concentration.

8. The method of claim 1, wherein the set of actual inputs includes a set of dosages of a drug.

9. The method of claim 1, wherein the set of actual inputs includes a set of drugs.

10. A device for predicting a time-dependent, pharmacokinetic response of a component of a mammalian system to an input into the system, the device comprising:

a processor;

a database for storing a set of actual input data, a set of time-dependent actual pharmacokinetic response data of a component comprising a body fluid, test input data, and time-dependent test pharmacokinetic response data of the component on a non-transitory computer readable medium;

an enumeration engine on a non-transitory computer readable medium to parameterize a non-compartmental model for predicting a test pharmacokinetic response of the component to a test input, the non-compartmental model comprising the formula

11. The device of claim 10, wherein the component is blood, blood plasma, or blood serum.

12. The device of claim 10, wherein the component is urine.

13. The device of claim 10, wherein the component saliva.

14. The device of claim 10, wherein the test pharmacokinetic response is a bacterial load.

15. The device of claim 10, wherein the test pharmacokinetic response is a viral load.

16. The device of claim 10, wherein the test pharmacokinetic response is a drug concentration.

17. The device of claim 10, wherein the set of actual inputs includes a set of dosages of a drug.

18. The device of claim 10, wherein the set of actual inputs includes a set of drugs.

19. A non-compartmental method of predicting a time-dependent, pharmacodynamic response of a component of a mammalian system to an input into the system, the method comprising:

selecting a component of the system, the component selected from the group consisting of a cell, a tissue, an organ, a DNA, a virus, a protein, an antibody, a bacteria;

selecting a set of actual inputs, the set of actual inputs having an element selected from the group consisting of a DNA, a virus, a protein, an antibody, a bacteria, a chemical, a dietary supplement, a nutrient, and a drug;

obtaining a set of time-dependent actual pharmacodynamic responses of the component to the set of actual inputs;

using the set of actual inputs and the set of time-dependent actual pharmacodynamic responses of the component to provide a model for predicting a test pharmacodynamic response of the component to a test input, the model comprising the formula

20. The method of claim 19, wherein the component is a bodily fluid selected from the group consisting of blood, blood plasma, blood serum, saliva, and urine.

21. The method of claim 19, wherein the component is a tumor cell.

22. The method of claim 19, wherein the component is a virus.

23. The method of claim 19, wherein the component is a bacteria.

24. The method of claim 19, wherein the test pharmacodynamic response is a bacterial load.

25. The method of claim 19, wherein the test pharmacodynamic response is a viral load.

26. The method of claim 19, wherein the test pharmacodynamic response is a tumor marker.

27. The method of claim 19, wherein the test pharmacodynamic response is a blood chemistry.

28. The method of claim 19, wherein the test pharmacodynamic response is a biomarker.

29. The method of claim 19, wherein the set of actual inputs includes a set of dosages of a drug.

30. The method of claim 19, wherein the set of actual inputs includes a set of drugs.

31. The method of claim 19, wherein the input is a diabetes drug, and the time-dependent pharmacodynamic response is glucose in the bloodstream.

32. A device for predicting a time-dependent pharmacodynamic response of a component of a mammalian system to an input into the system, the device comprising:

a processor;

a database for storing a set of actual input data, a set of time-dependent actual pharmacodynamic response data of a component, test input data, and time-dependent test pharmacodynamic response data of the component on a non-transitory computer readable medium;

an enumeration engine on a non-transitory computer readable medium to parameterize a non-compartmental model for predicting a test pharmacodynamic response of the component to a test input, the non-compartmental model comprising the formula

33. The device of claim 32, wherein the component is a bodily fluid selected from the group consisting of blood, blood plasma, blood serum, saliva, and urine.

34. The device of claim 32, wherein the component is a tumor cell.

35. The device of claim 32, wherein the component is a virus.

36. The device of claim 32, wherein the component is a bacteria.

37. The device of claim 32, wherein the test pharmacodynamic response is a bacterial load.

38. The device of claim 32, wherein the test pharmacodynamic response is a viral load.

39. The device of claim 32, wherein the test pharmacodynamic response is a tumor marker.

40. The device of claim 32, wherein the test pharmacodynamic response is a blood chemistry.

41. The device of claim 32, wherein the test pharmacodynamic response is a biomarker.

42. The device of claim 32, wherein the set of actual inputs includes a set of dosages of a drug.

43. The device of claim 32, wherein the set of actual inputs includes a set of drugs.

44. The device of claim 32, wherein the input is a diabetes drug, and the time-dependent pharmacodynamic response is glucose in the bloodstream.