Pharmacokinetic and pharmacodynamic modeling of erythropoietin administration

• US 6,747,002 B2
• Filed: 05/10/2000
• Issued: 06/08/2004
• Est. Priority Date: 05/11/1999
• Status: Expired due to Term

• Current Assignee: Janssen Pharmaceuticals, Inc. (Johnson & Johnson)
• Original Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Inventors: Cheung, Wing, Cote, Christine, Gibson, David, Vercammen, Els
• Primary Examiner(s): MORAN, MARJORIE A
• Application Number:
  US09/569,612
• Publication Number:
  US 20030198691A1
• Time in Patent Office: 1,490 Days
• Field of Search: 514/8, 530/351, 930/90, 702/19, 703/11
• US Class Current: 514/7.7
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/28 Compounds containing heavy metals
• CPC Class Codes: A61K 31/475 having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine vincamine A61K31/4375
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/14 Peptides containing saccharide radicals; Derivatives thereof , e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: G16C 20/30 Prediction of properties of chemical compounds, compositions or mixtures
• CPC Class Codes: G16H 50/50 : for simulation or modelling of medical disorders

Abstract

The present invention relates to systems and methods for obtaining optimized EPO dosage regimens for a desired pharmacodynamic/pharmacokinetic response. The system includes choosing one or more EPO dosage regimens, then using a PK/PD model to determine the pharmacodynamic/pharmacokinetic profile of one or more EPO dosage regimens, and finally selecting one of the EPO dosage regimens for administration to achieve the desired pharmacodynamic/pharmacodynamic response based on the EPO profile.

Claims

1. A method comprising the step of:

administering at least one EPO dose to a patient according to an EPO dosing regimen, wherein said regimen maintains at least a serum EPO concentration above a predose level for about 5 to about 30 days between EPO doses.

2. The method of claim 1, wherein said serum EPO concentration is sufficient to increase production of red blood cells.

3. The method of claim 2, wherein said serum EPO concentration is sufficient to maintain increased red blood cell production for at least one week.

4. The method of claim 2, wherein said serum EPO concentration is sufficient to maintain increased red blood cell production for at least two weeks.

5. The method of claim 1, wherein said EPO dosing regimen comprises administering EPO once a week.

6. The method of claim 5, wherein said once weekly EPO dosing regimen comprises administering a dose of EPO in the range of about 300 IU/kg to about 2400 IU/kg.

7. The method of claim 5, wherein said once weekly EPO dosing regimen comprises administering a dose of EPO in the range of about 30,000 IU to about 54,000 IU.

8. The method of claim 1, wherein said EPO dosing regimen comprises administering a dose of EPO once every two weeks.

9. The method of claim 8, wherein said once every two weeks EPO dosing regimen comprises administering a dose of EPO in the range of about 900 IU/kg to about 1200 IU/kg.

10. The method of claim 1, wherein said EPO dosing regimen comprises administering EPO once every ten days.

11. The method of claim 10, wherein said once every ten days EPO dosing regimen comprises administering a dose of EPO of about 900 IU/kg.

12. The method of claim 1, 3, 4, 5, 8, or 10, wherein said EPO dosing regimen comprises administering EPO selected from the group consisting of epoietin alpha and darbepoietin alpha.

13. The method of claim 1, wherein said EPO dosing regimen comprises administering EPO selected from the group consisting of novel erythropoeisis stimulating protein (NESP), human erythropoietin analog, and erythropoietin omega.

14. The method of claim 1, wherein said EPO dosing regimen comprises administering proteins having EPO biological activity.

15. The method of claim 14, wherein said proteins having EPO biological activity are selected from the group consisting of erythropoietin analogs, erythropoietin isoforms, and renal erythropoietin.

16. The method of claim 1, wherein said EPO dosing regimen comprises administering EPO derived from the group consisting of naturally occurring EPO, recombinant EPO, and synthetic EPO.

17. The method of claim 1, wherein said patient has anemia.

18. The method of claim 17, wherein said anemia comprises EPO concentration related anemia.

19. The method of claim 18, wherein said anemia is selected from the group consisting of end-stage renal failure, renal failure related anemia, and dialysis related anemia.

20. The method of claim 17, wherein said anemia comprises cancer chemotherapy related anemia.

21. The method of claim 17, wherein said anemia comprises AIDS drug therapy related anemia.

22. The method of claim 17, wherein said anemia comprises drug related anemia.

23. The method of claim 22, wherein said drug is selected from the group consisting of cisplatin and carboplatin.

24. The method of claim 22, wherein said drug is zidovudine.

25. The method of claim 1, wherein said patient is undergoing blood donation.

26. The method of claim 1, wherein said patient has received a bone marrow transplant.

27. The method of claim 1, wherein said patient has rheumatoid arthritis.

28. The method of claim 1, wherein said EPO dosing regimen comprises administering EPO via a route selected from the group consisting of intravenous administration, subcutaneous administration, and parental administration.

29. The method of claim 1, wherein said EPO dosing regimen comprises administering EPO having a modified glycosylation pattern.

30. The method of claim 29, wherein said EPO having a modified glycosylation pattern comprises darbepoietin alpha.