COMPOSITIONS AND METHODS FOR TREATING PIGMENTATION DISORDERS

1 . A method for treating hyperpigmentation or a pigmentation disorder or irregularity comprising locally or topically applying a therapeutically effective amount of a selective endothelin-A (ET-A) receptor antagonist or inhibitor to a mammal in need thereof.

2 . A method according to claim 1 wherein the selective endothelin-A (ET-A) receptor antagonist or inhibitor has a selectivity of at least two-fold over endothelin-B (ET-B), or a selectivity of at least five-fold over endothelin-B (ET-B)), or a selectivity of at least ten-fold over endothelin-B (ET-B)), or a selectivity of at least 100-fold over endothelin-B (ET-B)), or a selectivity of at least 1000-fold over endothelin-B (ET-B)), or a selectivity of at least 5000-fold over endothelin-B (ET-B).

3 . (canceled)

4 . (canceled)

5 . (canceled)

6 . (canceled)

7 . (canceled)

8 . A method according to claim 1 wherein the selective endothelin-A (ET-A) receptor antagonist or inhibitor is sitaxentan or a pharmaceutically acceptable salt thereof.

9 . A method according to claim 1 wherein the mammal is a human patient.

10 . A method according to claim 1 wherein the pigmentation disorder or irregularity is selected from postinflammatory hyperpigmentation, erythema dyschromicum perstans, lichen planus pigmentosus, melasma, lentigo, age spots, freckling, vitiligo, albinism, acanthosis nigricans, incontinentia pigmenti, progressive pigmentary purpura, xeroderma pigmentosum, café au lai spots or macules, cholasma, liver spots, Addison Disease, melanocytic naevi, sebhorreic keratosis, melanoma, basal cell carcinoma, pityriasis alba, pityriasis versicolor, idiopathic guttate hypomelanosis, progressive macular hypomelanosis, urticarial pigmentosa, and pigmentation changes caused by drug reactions, infections, burns, and chemical damage, and combinations thereof.

11 . A method according to claim 8 wherein the pharmaceutically acceptable salt is selected from an alkali metal salt, an alkaline earth metal salt, and an ammonium salt.

12 . A method according to claim 11 wherein the alkali metal salt is selected from lithium, sodium, and potassium.

13 . A method according to claim 11 wherein the alkali metal salt is sodium.

14 . (canceled)

15 . A method according to claim 1 wherein the selective endothelin-A (ET-A) receptor antagonist or inhibitor is applied at least one daily.

16 . A method according to claim 1 wherein the selective endothelin-A (ET-A) receptor antagonist or inhibitor is applied at least twice daily.

17 . A method according to claim 1 wherein the selective endothelin-A (ET-A) receptor antagonist or inhibitor is applied at least once weekly.

18 . A method according to claim 1 wherein the selective endothelin-A (ET-A) receptor antagonist or inhibitor is applied at least twice weekly.

19 . A method according to claim 1 wherein the selective endothelin-A (ET-A) receptor antagonist or inhibitor is applied at least once daily until the pigmentation disorder or irregularity is treated.

20 . A method according to claim 1 wherein the selective endothelin-A (ET-A) receptor antagonist or inhibitor is applied from a pharmaceutically acceptable composition.

21 . A method according to claim 1 for treating a pigmentation disorder or irregularity, comprising locally or topically applying a pharmaceutically acceptable composition comprising a therapeutically effective amount of sitaxentan or a pharmaceutically acceptable slat thereof.

22 . (canceled)

23 . (canceled)

24 . (canceled)

25 . (canceled)

26 . (canceled)

27 . A method according to claim 21 wherein the composition further comprises one or more sunscreen actives.

28 . A method according to claim 27 wherein the sunscreen active is selected from aminobenzoic acid, avobenzone, cinoxate, dioxybenzone, homosalate, menthyl anthranilate, octocrylene, octyl methoxycinnamate, octyl salicylate, oxybenzone, padimate O, phenylbenzimidazole sulfonic acid, sulisobenzone, titanium dioxide, trolamine salicylate, Zinc oxide, and combinations thereof.

29 . (canceled)

30 . (canceled)

31 . A method according to claim 21 in the form of a unit dosage composition.

32 . A method according to claim 31 wherein the unit dosage comprises from about 0.01 to about 1000 mg of sitaxentan or a pharmaceutically acceptable salt thereof, based on the weight of the sitaxentan active.

33 . A method according to claim 31 wherein the unit dosage comprises from about 0.001% to about 25% by weight sitaxentan or a pharmaceutically salt thereof, based on the weight of the sitaxentan active, or from about 0.01% to about 10% by weight sitaxentan or a pharmaceutically acceptable salt thereof, based on the weight of the sitaxentan active, or from about 0.1% to about 5% by weight sitaxentan or a pharmaceutically acceptable salt thereof, based on the weight of the sitaxentan active, or from about 0.2% to about 3% by weight sitaxentan or a pharmaceutically acceptable salt thereof, based on the weight of the sitaxentan active.

34 . (canceled)

35 . (canceled)

36 . (canceled)

37 . A method according to claim 31 wherein the unit dosage demonstrates at least one of the following pharmacokinetic parameters selected from a C max less than about 13 μg/ml, or a C max less than about 7 μg/ml, or an AUC less than about 40 μg hr/ml.

38 . (canceled)

39 . A composition for treating hyperpigmentation or a pigmentation disorder or irregularity for local or topical delivery comprising a therapeutically effective amount of a selective endothelin-A (ET-A) receptor antagonist or inhibitor and a pharmaceutically acceptable carrier.

40 . A composition according to claim 39 wherein the selective endothelin-A antagonist or inhibitor is sitaxentan or a pharmaceutically acceptable salt thereof