METHOD AND SYSTEM TO DEFINE PATIENT SPECIFIC THERAPEUTIC REGIMENS BY MEANS OF PHARMACOKINETIC AND PHARMACODYNAMIC TOOLS

• US 20110184379A1
• Filed: 03/27/2009
• Published: 07/28/2011
• Est. Priority Date: 03/27/2008
• Status: Abandoned Application

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Hamlen, Robert C., Van Antwerp, William P., Grovender, Eric A.
• Application Number:
  US12/934,054
• Publication Number:
  US 20110184379A1
• Time in Patent Office: Days
• US Class Current: 604/503
• CPC Class Codes: A61K 38/212 IFN-alpha
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients
• CPC Class Codes: G16H 40/63 for local operation
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders
• CPC Class Codes: G16H 70/20 relating to practices or guidelines

Abstract

Methods for treating Hepatitis infections are provided. In one embodiment, an initial dosage of interferon is administered to a patient, and interferon serum levels and viral load data is collected over time. This data can be used to determine patient-specific pharmacokinetic and pharmacodynamic parameters and then construct patient-specific interferon delivery profiles. Patient-specific delivery profiles can then be used to design patient-specific therapeutic regimens.

Claims

1. A method of using a patient-specific regimen responsiveness profile obtained from a patient infected with hepatitis C virus (HCV) to make a patient-specific therapeutic regimen, the method comprising:

administering at least one therapeutic agent to the patient following a first therapeutic regimen;

obtaining pharmacokinetic or pharmacodynamic parameters from the patient so as to observe a patient-specific response to the first therapeutic regimen, wherein the pharmacokinetic or pharmacodynamic parameters comprise at least one of;

a concentration of the therapeutic agent in the blood of the patient that results from the first therapeutic regimen;

or

a concentration of hepatitis C virus present in the patient;

using the pharmacokinetic or pharmacodynamic parameters observed in the patient in response to the first therapeutic regimen to obtain a patient-specific regimen responsiveness profile; and

using the patient-specific regimen responsiveness profile to make a first patient-specific therapeutic regimen.

2. The method of claim 1, wherein the first therapeutic regimen comprises interferon-α

and the first patient-specific therapeutic regimen is selected to;

maintain serum interferon-α

concentrations in the patient at a value greater than a EC₅₀, a concentration at which the effectiveness of interferon-α

is 50% of its maximum;

maintain serum interferon-α

concentrations in the patient at a value where the actual efficacy of interferon-α

in the patient is greater than the critical efficacy of interferon-α

;

modulate interferon-α

concentrations in the patient so that the patient is administered different interferon dosing regimens during different phases of hepatitis C viral load decline;

modulate interferon-α

concentrations in the patient so that a difference between the actual efficacy of interferon-α and

the critical efficacy of interferon-α

in the patient is increased;

or

modulate interferon-α

concentrations in the patient so as to reduce dose-dependent side effects observed during the administration of interferon-α

.

3. The method of claim 1, wherein the first therapeutic regimen comprises interferon-α

and the pharmacokinetic or pharmacodynamic parameters for a concentration of administered interferon-α

in the blood of the patient are obtained from the patient using an algorithm comprising;

4. The method of claim 1, wherein pharmacokinetic or pharmacodynamic parameters for a concentration of hepatitis C virus in the plasma of the patient are obtained from the patient using an algorithm comprising:

5. The method of claim 1, wherein the actual efficacy of the first therapeutic regimen is determined in the patient is calculated using an algorithm comprising:

V(t)=V_bar[1−

ε

+ε

e<sup>−

ct</sup>]

Wherein;

V(t) represents viral load (IU/ml);

V_bar represents initial viral load (IU/ml);

ε

represents actual efficacy;

t represents time (day); and

c represents clearance constant (day<sup>−

1</sup>).

6. The method of claim 1, wherein the first patient-specific therapeutic regimen is initiated when ratio of the number of HCV uninfected target cells to the number of HCV infected cells is greater than or equal to 1.

7. The method of claim 5, wherein the critical efficacy of the first therapeutic regimen is determined in the patient is calculated using an algorithm comprising:

8. The method of claim 1, further comprising using the patient-specific profile to assess the patient'"'"'s likely virological response to a defined interferon-α

composition or a defined interferon-α

dosing regimen.

9. The method of claim 1, including the further step of observing at least one patient-specific factor comprising:

a level of alanine transaminase, neopterin, 2′

,5′

oligo-adenylate synthetase, or aspartate transaminase in plasma of the patient;

a genotype or quasispecies of the hepatitis C virus;

a patient'"'"'s prior medical treatment history;

or

a presence or degree of a side effect that results from the first therapeutic regimen.

10. The method of claim 1, further comprising obtaining pharmacokinetic or pharmacodynamic parameters from the patient so as to observe a patient-specific response to the first patient-specific therapeutic regimen, wherein the pharmacokinetic or pharmacodynamic parameters comprise at least one of:

a concentration of administered interferon-α

in the plasma of the patient;

or

a concentration of hepatitis C virus in the plasma of the patient;

using the pharmacokinetic or pharmacodynamic parameters observed in the patient in response to the first patient-specific therapeutic regimen to obtain a second patient-specific regimen responsiveness profile; and

using the second patient-specific regimen responsiveness profile to make a second patient-specific therapeutic regimen.

11. The method of claim 1, wherein the first patient-specific therapeutic regimen comprises at least one of:

an interferon-α

;

ribavirin;

VX-950;

SCH 503034;

R1626;

or R71278.

12. The method of claim 1, wherein the first patient-specific therapeutic regimen comprises administering interferon-α

using a continuous infusion pump.

13. The method of claim 1, wherein the first patient-specific therapeutic regimen comprises administering a first dose of interferon-α

during a first phase of hepatitis C viral decline and a second dose of interferon-α

during a second phase of hepatitis C viral decline.

14. The method of claim 1, wherein the first patient-specific therapeutic regimen comprises administering a first dose of ribavirin during a first phase of hepatitis C viral decline and a second dose of ribavirin during a second phase of hepatitis C viral decline.

15. The method of claim 1, wherein the first patient-specific therapeutic regimen comprises administering a dose of interferon-α

for a period of time selected to maintain a plasma interferon-α

concentration above a set-point for the period of time.

16. A method of administering interferon-α

to a patient suffering from a Hepatitis C infection, the method comprising;

administering interferon-α

to the patient following a first therapeutic regimen;

obtaining pharmacokinetic or pharmacodynamic parameters from the patient to observe a patient-specific response to the first therapeutic regimen wherein the pharmacokinetic or pharmacodynamic parameters comprise at least one of;

a concentration of interferon-α

in the blood of the patient that results from the first therapeutic regimen;

or

a concentration of hepatitis C virus present in the patient;

using the pharmacokinetic or pharmacodynamic parameters observed in the patient in response to the first therapeutic regimen to make a patient-specific therapeutic regimen;

programming a controller operably coupled to a continuous infusion pump with patient-specific therapeutic regimen information; and

using the continuous infusion pump to administer interferon-α

to the patient according to the controller programming.

17. The method of claim 16, wherein the controller is programmed so that the continuous infusion pump administers interferon-α

in a manner that;

maintains serum interferon-α

concentrations in the patient at a value greater than a EC₅₀, a concentration at which the effectiveness of interferon-α

is 50% of its maximum;

maintains serum interferon-α

concentrations in the patient at a value where the actual efficacy of interferon-α

in the patient is greater than the critical efficacy of interferon-α

;

modulates interferon-α

concentrations in the patient so that the patient is administered different interferon dosing regimens during different phases of hepatitis C viral load decline;

modulates interferon-α

concentrations in the patient so that a difference between the actual efficacy of interferon-α and

the critical efficacy of interferon-α

in the patient is increased;

or

modulates interferon-α

concentrations in the patient so as to reduce adverse side effects observed during the administration of interferon-α

.

18. The method of claim 16, wherein pharmacokinetic or pharmacodynamic parameters are:

based upon observations of concentrations of interferon-α

in the blood of the patient following the first therapeutic regimen; and

are obtained using an algorithm comprising;

19. The method of claim 16, wherein:

the controller is programmed so that the continuous infusion pump administers interferon-α

at a dose and for a period of time selected to maintain a plasma interferon-α

concentration above a set-point for the period of time; and

the patient-specific therapeutic regimen further comprises administering a nucleoside analog that interferes with Hepatitis C viral replication.

20. A system for administering interferon to a patient having a hepatitis C infection, the system comprising:

a continuous infusion pump having a medication reservoir comprising interferon-α

;

a processor operably connected to the continuous infusion pump and comprising a set of instructions that causes the continuous infusion pump to administer the interferon-α

to the patient according to a patient-specific therapeutic regimen made by;

administering interferon-α

to the patient following a first therapeutic regimen;

obtaining pharmacokinetic or pharmacodynamic parameters from the patient so as to observe a patient-specific response to the first therapeutic regimen wherein the pharmacokinetic or pharmacodynamic parameters comprise at least one of;

a concentration of interferon-α

in the blood of the patient that results from the first therapeutic regimen;

or

a concentration of hepatitis C virus present in the patient;

using the pharmacokinetic or pharmacodynamic parameters observed in the patient in response to the first therapeutic regimen to obtain a patient-specific regimen responsiveness profile; and

using the patient-specific regimen responsiveness profile to make the patient-specific therapeutic regimen.

21. The system of claim 20, wherein the patient-specific therapeutic regimen maintains plasma interferon-α

levels in the patient above 20, 30, 40, 50, 60, 70, 80, 90, 100, 110 or 120 IU/mL.

22. The system of claim 20, wherein the patient-specific therapeutic regimen maintains plasma interferon-α

levels in the patient below 140, 130, 120, 110, 100, 90, 80, 70 or 60 IU/mL.

23. The system of claim 20, wherein the interferon-α

is not conjugated to a polyol.

24. The system of claim 20, wherein the continuous infusion pump:

has dimensions smaller than 15×

15 centimeters;

or

is operably coupled to an interface that facilitates the patient'"'"'s movements while using the continuous infusion pump, wherein the interface comprises a clip, a strap, a clamp or a tape.

25. A program code storage device, comprising:

a computer-readable medium;

a computer-readable program code, stored on the computer-readable medium, the computer-readable program code having instructions, which when executed cause a controller operably coupled to a medication infusion pump to administer the interferon-α

to a patient infected with the hepatitis C virus according to a patient-specific therapeutic regimen made by;

administering interferon-α

to the patient following a first therapeutic regimen;

obtaining pharmacokinetic or pharmacodynamic parameters from the patient so as to observe a patient-specific response to the first therapeutic regimen wherein the pharmacokinetic or pharmacodynamic parameters comprise at least one of;

a concentration of interferon-α

in the blood of the patient that results from the first therapeutic regimen;

or

a concentration of hepatitis C virus present in the patient;

using the pharmacokinetic or pharmacodynamic parameters observed in the patient in response to the first therapeutic regimen to obtain a patient-specific regimen responsiveness profile; and

using the patient-specific regimen responsiveness profile to make the patient-specific therapeutic regimen.