Method for use in treating a patient with FK 506 to prevent an adverse immune response

• US 5,365,948 A
• Filed: 08/21/1992
• Issued: 11/22/1994
• Est. Priority Date: 08/21/1992
• Status: Expired due to Fees

• Current Assignee: J & W Mcmichael Software Incorporated
• Original Assignee: J & W Mcmichael Software Incorporated
• Inventors: McMichael, John P.
• Primary Examiner(s): Sykes, Angela D.
• Application Number:
  US07/934,208
• Time in Patent Office: 823 Days
• Field of Search: 128/897-898, 364/413.01, 364/413.02, 540/455
• US Class Current: 128/898
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions

Abstract

A method and system for use in treating a patient with FK 506 to prevent an adverse immune response, either a rejection of a transplanted organ or an attack on the patient'"'"'s body by its own immune system caused by an autoimmune disease, without unduly suppressing the ability of the patient'"'"'s immune system to combat infection. The method employs an expert system to provide non-numerical information concerning the course of action to be taken with respect to a patient'"'"'s FK 506 treatment, at a given time, including, in particular, an instruction on whether the FK 506 dosage being administered to the patient should be changed, and if so how. That instruction is determined by the expert system through analysis of standardized characterizations assigned to standardized patient examination criteria provided to the expert system. The method also employs a means for determining the actual numerical FK 506 dosage the patient should receive at a given time.

Claims

1. A method for treating a patient to prevent an adverse immune response by partially suppressing the patient'"'"'s immune system without unduly suppressing the ability of the immune system to combat infection, comprising the steps of:

(a) administering an initial dose of FK 506 to the patient;

(b) examining the patient to determine information concerning patient examination criteria;

(c) assigning a characterization to each of the patient examination criteria, each such characterization being selected from a predetermined standardized range of characterizations applicable to each patient examination criterion;

(d) providing the assigned characterizations to a computing device comprising;

a knowledge base comprising rules which include one of a plurality of treatment instructions in response to at least one of various combinations of the characterizations which can be assigned to the patient examination criteria, and

an expert computer program including a first routine for prompting, through an output means, a user to enter, through an input means, the assigned characterizations;

a second routine for selecting a treatment instruction by locating a rule which covers the assigned characterizations, and thereby determines the treatment instruction; and

a third routine for communicating the treatment instruction to the output means;

(e) receiving from the computing device the treatment instruction; and

(f) administering a next FK 506 dose to the patient in accordance with the treatment instruction.

2. A method according to claim 1, which comprises the additional steps, after step (e) and before step (f), of:

(g) providing to the computing device data relating to a next FK 506 dosage determination, when the treatment instruction requires that the FK 506 dosage be changed; and

(h) receiving from the computing device the next FK 506 dosage, if one is determined;

wherein the expert computer program comprises a fourth routine for determining a next FK 506 dosage to be administered to the patient;

wherein the expert computer program contains at least one additional routine for receiving the data through the input means and communicating the next FK 506 dosage to the output means; and

wherein the next FK 506 dose administered to the patient is determined in accordance with the treatment instruction, and the next FK 506 dosage, if one is determined.

3. A method according to claim 2, wherein steps (b) through (h) are systematically repeated throughout the remainder of the patient'"'"'s life.

4. A method according to claim 2, wherein the patient is an organ transplant recipient and steps (b) through (h) are repeated every day for the first two weeks after the patient has been administered the initial dose of FK 506, then twice a week for the next two weeks, then weekly for the next two months, and then monthly for the rest of the patient'"'"'s life.

5. A method according to claim 2, wherein the patient is afflicted with an autoimmune disease and steps (b) through (h) are repeated twice a week for the first two weeks after the patient has been administered the initial dose of FK 506, then weekly for the next month, and then monthly for the rest of the patient'"'"'s life.

6. A method according to claim 2, wherein the data comprises the patient'"'"'s current FK 506 dosage, the patient'"'"'s current FK 506 blood plasma level and a desired FK 506 level for the patient;

and

wherein the fourth routine of the expert computer program determines the next FK 506 dosage by employing the following relationship;

space="preserve" listing-type="equation">ND=CD-((((CL-DL)/CL)/(1+(CD/40)))CD)

wherein,

ND=the next FK 506 dosage,

CD=the patient'"'"'s current FK 506 dosage,

CL=the patient'"'"'s current FK 506 blood plasma level, and

DL=the desired FK 506 level for the patient.

7. A method according to claim 2, wherein the data comprises the patient'"'"'s current FK 506 dosage;

and

wherein the fourth routine of the expert computer program determines a decreased next FK 506 dosage by searching through additional rules, contained in an additional knowledge base which can be accessed by the expert computer program, until an additional rule is found which covers the patient'"'"'s current FK 506 dosage and the characterization assigned to an FK 506 blood plasma level criterion, and thereby determines the decreased next FK 506 dosage; and

wherein the additional rules include one of a finite number of values for the decreased next FK 506 dosage in response to at least one of various combinations of characterizations which can be assigned to the FK 506 blood plasma level criterion and values for the patient'"'"'s current FK 506 dosage.

8. A method according to claim 2, wherein the data comprises the patient'"'"'s current FK 506 dosage, the patient'"'"'s current FK 506 blood plasma level and a desired FK 506 level for the patient;

and

wherein the fourth routine of the expert computer program determines the next FK 506 dosage by searching through additional rules, contained in an additional knowledge base which can be accessed by the expert computer program, until an additional rule is found which covers the patient'"'"'s current FK 506 dosage, the patient'"'"'s current FK 506 blood plasma level and the desired FK 506 level for the patient; and

wherein the additional rules include one of a finite number of values for the next FK 506 dosage in response to at least one of various combinations of values for the current FK 506 dosage, current FK 506 blood plasma level and the desired FK 506 level.

9. A method according to claim 1, wherein the patient is selected from the group consisting of heart and kidney transplant patients and the patient examination criteria comprise a toxicity criterion, a rejection criterion and an FK 506 blood plasma level criterion.

10. A method according to claim 1, wherein the patient is a liver transplant patient and the patient examination criteria comprise a toxicity criterion, a rejection criterion, an FK 506 blood plasma level criterion, a creatinine level criterion, a bilirubin level criterion, and a SGOT and SGPT levels criterion.

11. A method according to claim 1, wherein the patient is afflicted with an autoimmune disease and the patient examination criteria comprise a toxicity criterion, a desired effect criterion and an FK 506 blood plasma level criterion.

12. A method according to claim 1, comprising the additional step of performing an initial examination of the patient prior to administering the initial dose of FK 506 to the patient.

13. A method according to claim 1, wherein steps (b) through (f) are systematically repeated throughout the remainder of the patient'"'"'s life.

14. A method according to claim 1, wherein the patient is an organ transplant recipient and steps (b) through (f) are repeated every day for the first two weeks after the patient has been administered the initial dose of FK 506, then twice a week for the next two weeks, then weekly for the next two months, and then monthly for the rest of the patient'"'"'s life.

15. A method according to claim 1, wherein the patient is afflicted with an autoimmune disease and steps (b) through (f) are repeated twice a week for the first two weeks after the patient has been administered the initial dose of FK 506, then weekly for the next month, and then monthly for the rest of the patient'"'"'s life.

16. A method according to claim 1, wherein the patient is also treated with a dosage of at least one additional immunosuppressant agent.

17. A method according to claim 16, wherein the immunosuppressant agent is prednisone.

18. A method according to claim 17, wherein the computing device provides a prednisone treatment instruction after (i) the patient has received an initial dose of prednisone, (ii) a prednisone dosage criterion is assigned a characterization from a predetermined range of standardized prednisone characterizations, and (iii) the characterization assigned to the prednisone dosage criterion is provided to the computing device in the first routine;

the prednisone treatment instruction being provided through means of a first prednisone treatment instruction routine which searches through a prednisone treatment knowledge base containing prednisone treatment rules until a prednisone treatment rule is found which covers the characterizations assigned to an efficacy criterion and the prednisone dosage criterion, and thereby determines the prednisone treatment instruction; and

a second prednisone treatment routine for communicating the prednisone treatment instruction to the output means;

wherein the prednisone treatment instruction rules include one of a plurality of prednisone treatment instructions in response to at least one of various combinations of characterizations which can be assigned to the efficacy criterion and the prednisone dosage criterion.

19. A method according to claim 18, wherein the patient is the recipient of a transplanted organ and the efficacy criterion is a rejection criterion.

20. A method according to claim 18, wherein the patient is afflicted with an autoimmune disease and the efficacy criterion is a desired effect criterion.

21. A method according to claim 18, wherein the computing device provides a next prednisone dosage, if a decrease in the prednisone dosage is required by the prednisone treatment instruction.

22. A method according to claim 1, wherein the computing device determines at least one characterization to be assigned to a toxicity criterion through means of additional expert computer program routines comprising:

a first routine for receiving characterizations assigned to toxicity determination criteria;

a second routine which searches through a toxicity determination knowledge base containing toxicity determination rules until a toxicity determination rule is found which covers the toxicity determination characterizations assigned to the toxicity determination criteria, and thereby determines at least one characterization to be assigned to the toxicity criterion; and

a third routine for communicating to the output means the characterization to be assigned to the toxicity criterion;

wherein the toxicity determination rules include at least one of the characterizations which can be assigned to the toxicity criterion in response to at least one of various combinations of the characterizations which can be assigned to the toxicity determination criteria.

23. A method according to claim 22, wherein the toxicity determination criteria comprise a tingling/loss of sensation toxicity determination criterion, a tremor toxicity determination criterion, a trouble sleeping toxicity determination criterion, a diabetogenicity toxicity determination criterion, and a change in creatinine level toxicity determination criterion.

24. A method for treating a patient to prevent an adverse immune response by partially suppressing the patient'"'"'s immune system without unduly suppressing the ability of the immune system to combat infection, comprising the steps of:

(a) administering an initial dose of FK 506 to the patient;

(b) examining the patient to determine the patient'"'"'s current FK 506 blood plasma level;

(c) assigning a characterization to the patient'"'"'s current FK 506 blood plasma level from a predetermined standardized range of characterizations;

(d) providing the patient'"'"'s current FK 506 dosage and the characterization assigned to the patient'"'"'s current FK 506 blood plasma level to a computing device comprising;

a knowledge base comprising rules which include one of a finite number of values for a decreased next FK 506 dosage in response to at least one of various combinations of characterizations which can be assigned to the patient'"'"'s current FK 506 blood plasma level and values for the patient'"'"'s current FK 506 dosage; and

an expert computer program including a first routine for prompting, through an output means, a user to enter, through an input means, the patient'"'"'s current FK 506 dosage and the characterization assigned to the patient'"'"'s current FK 506 blood plasma level;

a second routine for selecting the next FK 506 dosage by locating the rule which covers the patient'"'"'s current FK 506 dosage and the characterization assigned to the patient'"'"'s current FK 506 blood plasma level, and thereby determines the decreased next FK 506 dosage; and

a third routine for communicating the decreased next FK 506 dosage to the output means;

(e) receiving from the computing device the decreased next FK 506 dosage; and

(f) administering a next FK 506 dose in accordance with the decreased next FK 506 dosage determined by the computing device.

25. A method for treating a patient to prevent an adverse immune response by partially suppressing the patient'"'"'s immune system without unduly suppressing the ability of the immune system to combat infection, comprising the steps of:

(a) administering an initial dose of FK 506 to the patient;

(b) examining the patient to determine the patient'"'"'s current FK 506 blood plasma level;

(c) determining a desired FK 506 level for the patient;

(d) providing the patient'"'"'s current FK 506 dosage, the patient'"'"'s current FK 506 blood plasma level and the desired FK 506 level for the patient to a computing device comprising;

a knowledge base comprising rules which include one of a finite number of values for a next FK 506 dosage in response to at least one of various combinations of values for the current FK 506 dosage, current FK 506 blood plasma level and the desired FK 506 level; and

an expert computer program including a first routine for prompting, through an output means, a user to enter, through an input means, the patient'"'"'s current FK 506 dosage, the patient'"'"'s current FK 506 blood plasma level and the desired FK 506 level for the patient;

a second routine for selecting the next FK 506 dosage by locating the rule which covers the patient'"'"'s current FK 506 dosage, the patient'"'"'s current FK 506 blood plasma level and the desired FK 506 level for the patient, and thereby determines the next FK 506 dosage; and

a third routine for communicating the next FK 506 dosage to the output means;

(e) receiving from the computing device the next FK 506 dosage; and

(f) administering a next FK 506 dose in accordance with the next FK 506 dosage determined by the computing device.

26. A method according to claim 25, wherein steps (b) through (f) are systematically repeated throughout the remainder of the patient'"'"'s life.

27. A method according to claim 25, wherein the patient is an organ transplant recipient and steps (b) through (f) are repeated every day for the first two weeks after the patient has been administered the initial dose of FK 506, then twice a week for next two weeks, then weekly for the next two months, and then monthly for the rest of the patient'"'"'s life.

28. A method according to claim 25, wherein the patient is afflicted with an autoimmune disease and steps (b) through (f) are repeated twice a week for the first two weeks after the patient has been administered the initial dose of FK 506, then weekly for the next month, and then monthly for the rest of the patient'"'"'s life.

29. A method according to claim 25, wherein the patient is also treated with a dosage of at least one additional immunosuppressant agent.

30. A method according to claim 29, wherein the immunosuppressant agent is prednisone.

31. A method for treating a patient to prevent an adverse immune response by partially suppressing the patient'"'"'s immune system without unduly suppressing the ability of the immune system to combat infection, comprising the steps of:

(a) administering an initial dose of FK 506 to the patient;

(b) examining the patient to determine the patient'"'"'s current FK 506 blood plasma level;

(c) determining a desired FK 506 level for the patient;

(d) employing the following relationship along with the patient'"'"'s current FK 506 dosage, the patient'"'"'s current FK 506 blood plasma level, and the desired FK 506 level for the patient to determine a next FK 506 dosage;

space="preserve" listing-type="equation">ND=CD-((((CL-DL)/CL)/(1+(CD/40)))CD),

wherein,

ND=the next FK 506 dosage,

CD=the patient'"'"'s current FK 506 dosage,

CL=the patient'"'"'s current FK 506 blood plasma level, and

DL=the desired FK 506 level for the patient; and

(e) administering a next dose of FK 506 to the patient in accordance with the next FK 506 dosage determined from the relationship.

33. A method according to claim 31 or 32, wherein steps (b) through (e) are systematically repeated throughout the remainder of the patient'"'"'s life.

34. A method according to claim 31 or 32, wherein the patient is an organ transplant recipient and steps (b) through (e) are repeated every day for the first two weeks after the patient has been administered the initial dose of FK 506, then twice a week for next two weeks, then weekly for the next two months, and then monthly for the rest of the patient'"'"'s life.

35. A method according to claim 31 or 32, wherein the patient is afflicted with an autoimmune disease and steps (b) through (e) are repeated twice a week for the first two weeks after the patient has been administered the initial dose of FK 506, then weekly for the next month, and then monthly for the rest of the patient'"'"'s life.

36. A method according to claim 31 or 32, wherein the patient is also treated with a dosage of at least one additional immunosuppressant agent.

37. A method according to claim 36, wherein the immunosuppressant agent is prednisone.

32. A method for treating a patient to prevent an adverse immune response by partially suppressing the patient'"'"'s immune system without unduly suppressing the ability of the system to combat infection, comprising the steps of:

(a) administering an initial dose of FK 506 to the patient;

(b) examining the patient to determine the patient'"'"'s current FK 506 blood plasma level;

(c) determining a desired FK 506 level for the patient;

(d) employing the following relationship along with the patient'"'"'s current FK 506 dosage, the patient'"'"'s current FK 506 blood plasma level, and a potential next FK 506 dosage to determine a next FK 506 dosage by finding a potential next FK 506 dosage which will provide a potential desired FK 506 level which corresponds to the desired FK 506 level for the patient;

space="preserve" listing-type="equation">PDL=(((PND-CD)/CD)(1+(CD /

     40))(CL))+CL

wherein,

PND=the potential next FK 506 dosage,

CD=the patient'"'"'s current FK 506 dosage,

CL=the patient'"'"'s current FK 506 blood plasma level, and

PDL=the potential desired FK 506 level; and

(e) administering a next dose of FK 506 to the patient in accordance with the next FK 506 dosage determined from the relationship.