METHODS OF TREATING UREA CYCLE DISORDERS
The present disclosure provides novel methods for determining an effective dosage of a PAA prodrug and for treating a UCD that incorporate body surface area and urinary PAGN concentration. The disclosure further provides novel methods for assessing compliance with PAA prodrug administration that incorporate urinary PAGN concentration, and the subject's current dosing regimen, BSA, or age. The disclosure further provides novel methods of treating a UCD in a subject in need thereof that incorporate urinary PAGN concentration, and the subject's current dosing regimen, BSA, and/or age.
1 .- 20 . (canceled)
21 . A method for determining or adjusting an effective dosage of a phenylacetic acid (PAA) prodrug to be administered to a subject with a urea cycle disorder, comprising:
calculating the body surface area (BSA) of the subject; and
administering an effective dosage of the PAA prodrug to the subject wherein the effective dosage of the PAA prodrug is a first dosage if the BSA is at or above 1.3 m 2 or a second dosage if the BSA is below 1.3 m 2 , and wherein the second dosage is higher than the first dosage.
22 . The method of claim 21 , wherein the PAA prodrug is glyceryl tri-[4-phenylbutyrate].
23 . The method of claim 21 , wherein the subject has previously been administered an initial dosage of an initial PAA prodrug.
24 . The method of claim 23 , wherein the initial PAA prodrug is glyceryl tri-[4-phenylbutyrate].
25 . The method of claim 23 , wherein the initial dosage of the glyceryl tri-[4-phenylbutyrate] is 5 to 12.4 g/m 2 /day.
26 . The method of claim 25 , wherein the effective dosage of the PAA prodrug is 5.33 to 8.79 g/m 2 /day.
27 . The method of claim 26 , wherein the PAA prodrug is glyceryl tri-[4-phenylbutyrate].
28 . The method of claim 25 , wherein the effective dosage of the PAA prodrug is 6.25 to 9.9 g/m 2 /day.
29 . The method of claim 28 , wherein the PAA prodrug is glyceryl tri-[4-phenylbutyrate].
30 . The method of claim 21 , wherein the subject is under the age of 12.
31 . The method of claim 21 , wherein the PAA prodrug is administered orally.
32 . A method for treating a urea cycle disorder in a subject in need thereof wherein the subject has a body surface area (BSA) at or above 1.3 m 2 , comprising:
administering to the subject an effective dosage of glyceryl tri-[4-phenylbutyrate] of 5.33 to 8.79 g/m 2 /day.
33 . The method of claim 32 , wherein the subject is under the age of 12.
34 . The method of claim 32 , wherein the glyceryl tri-[4-phenylbutyrate] is administered orally.
35 . The method of claim 32 , wherein the subject has not previously been administered a PAA prodrug.