Administration of sapropterin: how do you take it?
Research type
Research Study
Full title
Administration of sapropterin: is patient practice associated with best efficacy?
IRAS ID
361954
Contact name
Anita MacDonald
Contact email
Sponsor organisation
Birmingham Women's and Children's NHS Foundation Trust
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
0 years, 6 months, 0 days
Research summary
Research Summary:
Sapropterin, a synthetic version of tetrahydrobiopterin, is the first UK pharmaceutical treatment approved for Phenylketonuria (PKU). It lowers blood phenylalanine (Phe) levels and increases Phe tolerance in a subset of around 30% of patients. It works by enhancing residual enzyme activity. Overall, limited attention is given to the way that sapropterin is administered. In clinics, it is recorded that the dose of medication is taken, but the timing of administration or if the drug is taken with or without food may remain unchecked. Sapropterin has a low efficiency of uptake and retention in the body. Patients with PKU may not take sapropterin in a manner that optimises its bioavailability. In the pharmaceutical ‘summary of product characteristics’, it is recommended that
sapropterin tablets should be administered with a meal, taken as a single daily dose, the same time each day, preferably in the morning. There is now increasing evidence to show that its efficacy may be increased if taken twice daily. We aim to conduct a patient questionnaire to examine sapropterin administration to patients in the UK, in order to make recommendations to improve practical methods of administering the drug. This will improve Phe tolerance and blood Phe control.Summary of Results:
Sapropterin dihydrochloride is an established treatment option for individuals with phenylketonuria (PKU) who demonstrate responsiveness, but un-certainty persists regarding dosing frequency, timing relative
to meals, the influence of dietary composition, and efficacy of different formulations. Despite widespread use in the UK, real‑world administration behaviours have not previously been characterised. This study aimed to characterise real world sapropterin administration
behaviours among people with PKU in the UK. Methods: A 31‑item questionnaire was developed and disseminated via the National Society for Phenylketonuria website and social media channels. The survey captured demographic information, dosing schedules, formulation
use, administration techniques, co‑ingestion with food, and changes in natural protein tolerance following initiation of generic sapropterin. Results: 123 sapropterin users completed the survey. Most respondents were caregivers of children or adolescents (69%
aged 0–18 years). Once‑daily dosing was most common (66%, n=81), typically administered at breakfast, followed by twice‑daily (33%, n=40) and three‑times‑daily (1.6%, n=2). Tablets were the predominant formulation (93%, n=114); 51% (n=58) swallowed tablets
whole, while others crushed or dissolved them in water or juice. Nine respondents (7%) used powder sachets. Most participants (75%, n=92) took sapropterin with food, with both low‑fat (37%) and high‑fat (26%) meals reported. Natural protein tolerance increased
significantly across the cohort (p<0.001), ranging from 65% to >447%. Adults (p<0.001) and individuals swallowing tablets whole experienced significantly greater increases (p=0.038). Fifteen percent achieved an unrestricted diet, and although 72% were pleased
with their increased protein allowance, many expressed a desire for further improvement. Conclusions: Substantial heterogeneity in dosing schedules, formulation handling, and co-ingestion practices highlights the absence of standardised guidance. These findings
emphasise the need for clearer clinical recommendations to optimise treatment effectiveness and support consistent, equitable care.REC name
London - Brighton & Sussex Research Ethics Committee
REC reference
25/PR/1344
Date of REC Opinion
22 Oct 2025
REC opinion
Further Information Favourable Opinion