METHODS FOR TREATING CHOLESTASIS
Provided herein are methods for treating cholestasis in a subject having a liver disease. The method includes administering to the subject an Apical Sodium-dependent Bile Acid Transporter (ASBTI). More specifically, the present invention relates to methods for treating cholestasis in a subject where the method includes administering an ASBTI to a subject at a dose of at least 10 μg/kg/day.
1 . A method for treating biliary atresia in a subject comprising administering to the subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI), wherein the ASBTI is
and wherein the ASBTI is administered in an amount of from about 400 μg/kg/day to about 1400 μg/kg/day.
2 .- 17 . (canceled)
18 . The method of m claim 1 , wherein the subject is a pediatric subject.
19 . The method of claim 1 , wherein the ASBTI is administered once daily (QD).
20 . The method of claim 1 , wherein the ASBTI is administered twice daily (BID).
21 . The method of claim 1 , wherein the ASBTI is administered in an amount of from about 400 μg/kg/day to about 1200 μg/kg/day.
22 . The method of claim 1 , wherein the ASBTI is administered in an amount of from about 400 μg/kg/day to about 800 μg/kg/day.
23 . The method of claim 1 , wherein the administration of the ASBTI reduces a symptom or changes a disease-relevant laboratory measure of the biliary atresia that is maintained for at least one year.
24 . The method of claim 23 , wherein the reduction in the symptom or the change in a disease-relevant laboratory measure comprises a reduction in sBA concentration, an increase in serum 7α-hydroxy-4-cholesten-3-one (7αC4) concentration, an increase in a ratio of serum 7αC4 concentration to serum bile acids (sBA) concentration (7αC4:sBA), a reduction in pruritis, an increase in a quality of life inventory score, an increase in a quality of life inventory score related to fatigue, an increase in growth, or a combination thereof.
25 . The method of claim 24 , wherein the reduction in the symptom or a change in a disease-relevant laboratory measure is determined relative to a baseline level.
26 .- 34 . (canceled)
35 . The method of claim 1 , wherein the administration of the ASBTI results in a decrease in sBA concentration of at least about 70% relative to baseline.
36 . The method of claim 1 , wherein the administration of the ASBTI results in a reduction in severity of pruritus.
37 .- 41 . (canceled)
42 . The method of claim 1 , wherein serum bilirubin concentration is at about pre-administration baseline level at about 4 months after first administration of the ASBTI.
43 . The method of claim 1 , wherein serum alanine aminotransferase (ALT) concentration is at about pre-administration baseline level at about 4 months after first administration of the ASBTI.
44 . The method of claim 1 , wherein serum aspartate aminotransferase (AST) concentration, and serum bilirubin concentration are within a normal range at about 4 months after first administration of the ASBTI.
45 .- 102 . (canceled)
103 . The method of claim 1 , wherein the biliary atresia is post-Kasai biliary atresia.
104 . The method of claim 1 , wherein the biliary atresia is post liver transplantation biliary atresia.
105 . The method of claim 1 , wherein the ASBTI is administered in an amount of about 300 μg/kg twice a day.
106 . The method of claim 1 , wherein the ASBTI is administered in an amount of about 600 μg/kg/day.