Improved metabolic control in tetrahydrobiopterin (BH4), responsive phenylketonuria with sapropterin administered in two divided doses vs. a single daily dose

• Published in: Journal of pediatric endocrinology & metabolism : JPEM Vol. 30; no. 7; p. 713
• Main Authors: Kör, Deniz, Yılmaz, Berna Şeker, Bulut, Fatma Derya, Ceylaner, Serdar, Mungan, Neslihan Önenli
• Format: Journal Article
• Language: English
• Published: Germany 26-07-2017
• Subjects: Adult; Biopterins - administration & dosage; Biopterins - analogs & derivatives; Case-Control Studies; Diet; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Phenylalanine - blood; Phenylalanine Hydroxylase - metabolism; Phenylketonurias - blood; Phenylketonurias - drug therapy; Prognosis; divided daily doses; phenylketonuria; BH4
• ISSN: 2191-0251
• DOI: 10.1515/jpem-2016-0461

Phenylketonuria (PKU) often requires a lifelong phenylalanine (Phe)-restricted diet. Introduction of 6R-tetrahydrobiopterin (BH4) has made a huge difference in the diets of patients with PKU. BH4 is the co-factor of the enzyme phenylalanine hydroxylase (PAH) and improves PAH activity and, thus, Phe tolerance in the diet. A limited number of published studies suggest a pharmacodynamic profile of BH4 more suitable to be administered in divided daily doses.
After a 72-h BH4 loading test, sapropterin was initiated in 50 responsive patients. This case-control study was conducted by administering the same daily dose of sapropterin in group 1 (n=24) as a customary single dose or in two divided doses in group 2 (n=26) over 1 year.
Mean daily consumption of Phe increased significantly after the first year of BH4 treatment in group 2 compared to group 1 (p<0.05). At the end of the first year of treatment with BH4, another dramatic difference observed between the two groups was the ability to transition to a Phe-free diet. Eight patients from group 2 and two from group 1 could quit dietary restriction.
When given in two divided daily doses, BH4 was more efficacious than a single daily dose in increasing daily Phe consumption, Phe tolerance and the ability to transition to a Phe-unrestricted diet at the end of the first year of treatment.