TREATMENT OF UREA CYCLE DISORDERS IN NEONATES AND INFANTS
Nitrogen scavenging drugs such as glycerol phenylbutyrate can be administered safely to infants and toddlers with urea cycle disorders by adjusting the dosage based on one or more biomarkers selected from the group consisting of urinary-PAGN and plasma PAA:PAGN ratio.
1 . A method of administering glycerol phenylbutyrate to a patient in need thereof, wherein said patient is between 2 months of age to less than 2 years of age, comprising
administering daily to the patient a therapeutically effective amount of the glycerol phenylbutyrate in three or more equally divided doses.
2 . The method of claim 1 , further comprising restricting the patient's dietary protein.
3 . The method of claim 1 , further comprising monitoring the patient's plasma ammonia levels to determine the need for dosage titration of the glycerol phenylbutyrate.
4 . The method of claim 3 , further comprising adjusting the glycerol phenylbutyrate dosage to keep the first ammonia of the morning below the upper limit of normal.
5 . The method of claim 1 , wherein the glycerol phenylbutyrate is administered orally.
6 . The method of claim 1 , wherein the glycerol phenylbutyrate is administered using a nasogastric and/or gastrostomy tube.
7 . The method of claim 6 , wherein the volume of glycerol phenylbutyrate administered is less than 1 mL per dose and the method further comprises monitoring the patient's ammonia level.
8 . The method of claim 1 , wherein the patient previously was administered phenylbutyrate.
9 . The method of claim 1 , wherein the patient previously had not been administered phenylbutyrate.
10 . The method of claim 1 , wherein the therapeutically effective amount of the glycerol phenylbutyrate is 4.5 to 11.2 mL/m 2 /day (5 to 12.4 g/m 2 /day).
11 . The method of claim 1 , wherein the therapeutically effective amount of the glycerol phenylbutyrate is 4.8 to 11.5 mL/m 2 /day (5.3 to 12.6 g/m 2 /day).
12 . The method of claim 1 , wherein the therapeutically effective amount of the glycerol phenylbutyrate is 3.3 to 12.3 mL/m 2 /day (3.7 to 13.5 g/m 2 /day).
13 . The method of claim 1 , wherein the therapeutically effective amount of the glycerol phenylbutyrate is 4.5 mL/m 2 /day (5 g/m 2 /day).
14 . The method of claim 1 , wherein the therapeutically effective amount of the glycerol phenylbutyrate is 8 mL/m 2 /day (8.8 g/m 2 /day).
15 . The method of claim 1 , wherein the therapeutically effective amount of the glycerol phenylbutyrate is 7.5 mL/m 2 /day (8.2 g/m 2 /day).
16 . The method of claim 1 , further comprising obtaining measurements of plasma phenylacetate (PAA) concentrations and the ratio of plasma PAA to phenylacetylglutamine (PAGN).
17 . The method of claim 1 , further comprising obtaining measurements of urinary phenylacetylglutamine (U-PAGN).
18 . The method of claim 17 , wherein if the U-PAGN excretion is insufficient to cover daily dietary protein intake and/or the fasting ammonia is greater than half the upper limit of normal, the method further comprises increasing the glycerol phenylbutyrate dosage.
19 . The method of claim 1 , wherein the glycerol phenylbutyrate is administered just prior to breastfeeding or intake of formula or food.
20 . The method of claim 1 , wherein the glycerol phenylbutyrate is administered three to six times daily.