Sapropterin: a new therapeutic agent for phenylketonuria.
OBJECTIVE
To summarize the role of pharmacotherapy in the management of phenylketonuria (PKU) and to review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and safety profile of sapropterin for this indication.


METHODS
A literature search was conducted using MEDLINE (1966-May 2009), International Pharmaceutical Abstracts (1970-May 2009), and Cochrane database (2008) for the following key words: sapropterin, tetrahydrobiopterin, phenylketonurias, and phenylalanine.


METHODS
English-language studies involving humans examining the role of tetrahydrobiopterin (BH4) in the management of PKU were reviewed to evaluate the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and safety profile for sapropterin. All Phase 2 and 3 randomized controlled trials assessing the safety and efficacy of sapropterin were included in this literature evaluation.


RESULTS
Sapropterin represents the only Food and Drug Administration-approved medication for BH4-responsive PKU, marking an important advance in the treatment of this condition. Among individuals with hyperphenylalaninemia and some residual phenylalanine hydroxylase function, sapropterin can enhance activity of this enzyme to decrease serum phenylalanine concentrations. Sapropterin has been compared with placebo in one Phase 2 and one Phase 3 clinical trial, demonstrating significantly better response rates. Based on available studies, this agent appears to be safe and well tolerated, with adverse event rates similar to those of placebo. However, additional studies are warranted to assess the long-term safety and efficacy of sapropterin therapy.


CONCLUSIONS
Sapropterin offers a promising therapeutic option for select individuals with BH4-responsive PKU, although long-term data are limited evaluating its safety and efficacy in traditional clinical practice settings. When considering sapropterin therapy, clinicians must consider factors such as cost and patient adherence to drug therapy and/or diet.
Hegge
Karly A
KA
Falls Community Health; College of Pharmacy, South Dakota State University, Sioux Falls, SD 57106, USA. karly.hegge@sdstate.edu
Horning
Kristin K
KK
Peitz
Gregory J
GJ
Hegge
Kassy
K
D001708:Biopterins / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic
D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin