A Prospective Population Pharmacokinetic Analysis of Sapropterin Dihydrochloride in Infants and Young Children with Phenylketonuria

Background and Objectives Untreated phenylketonuria (PKU), a hereditary metabolic disorder caused by a genetic mutation in phenylalanine hydroxylase (PAH), is characterized by elevated blood phenylalanine (Phe) and severe neurologic disease. Sapropterin dihydrochloride, a synthetic preparation of naturally occurring PAH cofactor tetrahydrobiopterin (BH4), activates residual PAH in a subset of patients, resulting in decreased blood Phe and increased Phe tolerance. The objective of this study was to determine the appropriate dose of sapropterin in pediatric patients (0–6 years). The study design used D-optimization and was prospectively powered to achieve precise estimates of clearance and volume of distribution.