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Details for Patent: 6,586,476

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Details for Patent: 6,586,476

Title: Methods for the treatment of nephro-disorders using aminothiol compounds
Abstract:The present invention relates to new uses of S-2-(3-aminopropylamino)ethyl dihydrogen phosphorothioate, (amifostine) and other aminothiol compounds to treat and reverse toxicities caused by therapeutic agents, radiation treatment or diabetes. In particular, the invention provides a method for treating neurotoxicity and nephrotoxicity associated with the administration of chemotherapeutic agents.
Inventor(s): Stogniew; Martin (Blue Bell, PA), Alberts; David S. (Tucson, AZ), Kaplan; Edward H. (Skokie, IL)
Assignee: MedImmune Oncology, Inc. (Gaithersburg, MD)
Filing Date:Oct 28, 1999
Application Number:09/429,290
Claims:1. A method for treating a nephro-disorders in a human which comprises administering a therapeutically effective amount of one or more aminothiol compounds, or a pharmaceutically acceptable salt thereof, to a human in need of such treatment after the occurrence of said nephro-disorders.

2. The method of claim 1, wherein said nephro-disorder is chemically induced, drug induced, induced by aging, induced by exposure to radiation, induced by diabetes or induced by an unknown etiology.

3. The method of claim 2 wherein said nephro-disorder is induced by diabetes.

4. The method of claim 1, wherein said nephro-disorder is a nephrotoxicity associated with the administration of radiation therapy of one or more therapeutic agent(s).

5. The method of claim 1 wherein said nephro-disorder is characterized by elevations in BUN, serum creatinine, or a decrease in creatinine clearance or sodium magnesium or a combination thereof.

6. The method of claim 4 wherein said therapeutic agent is an antiviral, an antibiotic, an antifungal, a contrast agent or a combination thereof.

7. The method of claim 1 wherein said nephro-disorder is a result of the administration of cisplatin, carboplatin, pactitaxel, docetaxel, vincristine, navelbine, gemcytobin, etoposide, doxorubicin, daunorubicin or a combination thereof.

8. The method of claim 1 wherein said nephro-disorder is a result of the administration of 3'-azido-3'-deoxythymidine (AZT), d4T (stavadine), ddI (didanosine), ddC (zalcitabine), 3TC (lamivudine), gentamicin, tobramicin, kanamicin, amikacin, vancamicin, amphotericin B or a combination thereof.

9. The method of claim 1, wherein said aminothiol compound is administered intravenously, subcutaneously, intramuscularly, intradermally, topically or orally.

10. The method of claim 1 wherein said human is a cancer patient, AIDS patient, diabetic, or hypertensive patient.

11. The method of claim 1 wherein said aminothiol compound is a compound of the formula:

or a pharmaceutically acceptable addition salt or hydrate thereof, wherein R.sub.1 is hydrogen, C.sub.5 -C.sub.7 aryl, C.sub.2 -C.sub.7 acyl, or C.sub.1 -C.sub.7 alkyl; R.sub.2 is hydrogen, PO.sub.3 H.sub.2 or R.sub.3 wherein R.sub.3 is R.sub.1 NH(CH.sub.2).sub.n NH(CH.sub.2).sub.m S--; n is an integer from 1 to 10; and m is an integer from 1 to 10.

12. The method of claim 11, wherein said compound is selected from the group consisting of WR-1065, WR-151326, WR-151327, WR-638, WR-3689, WR-2822, WR-2529, WR-77913, WR-255591, WR-2823, WR-255709 and salts or hydrates thereof.

13. The method of claim 1, wherein said aminothiol is amifostine.

14. The method of claim 1, wherein said aminothiol is WR-33278.

15. The method of claim 1, wherein said aminothiol is an active metabolite of WR-2721.

16. The method of claim 1, wherein said aminothiol is a prodrug of an active metabolite of WR-2721.

17. The method of claim 1, wherein said aminothiol is administered one or more days after the occurrence of said nephro-disorders.

18. The method of claim 1, wherein two or more aminothiol compounds are administered.

19. The method of claim 1, wherein the amount administered is from about 10 mg/m.sup.2 to about 2,000 mg/m.sup.2.
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