Sapropterin

Sapropterin (IUPAC name: 2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydro-4H-chromen-4-one), also known by its brand name Kuvan, is a synthetic form of the naturally occurring cofactor tetrahydrobiopterin (BH4). It is primarily used as a medication to treat phenylketonuria (PKU), a genetic disorder that results in decreased metabolism of the amino acid phenylalanine. Sapropterin works by enhancing the activity of phenylalanine hydroxylase, the enzyme deficient in individuals with PKU, thereby reducing the levels of phenylalanine in the blood.

Medical Uses

Sapropterin is indicated for the treatment of phenylketonuria (PKU) in patients who have been shown to be responsive to such treatment. Responsiveness to sapropterin is determined through a controlled trial of the drug under the supervision of a healthcare provider. It is used alongside a phenylalanine-restricted diet to manage blood phenylalanine levels within a normal range.

Mechanism of Action

Sapropterin acts as a cofactor for the enzyme phenylalanine hydroxylase (PAH), enhancing its activity. PAH is responsible for the conversion of phenylalanine to tyrosine, a process that is inefficient in individuals with PKU. By increasing the activity of PAH, sapropterin helps lower the elevated levels of phenylalanine in the blood, thereby reducing the risk of neurological damage and other complications associated with PKU.

Administration

Sapropterin is administered orally, usually in the form of tablets that are dissolved in water or apple juice before ingestion. The dosage and duration of treatment depend on the patient's age, weight, and level of phenylalanine in the blood, and should be adjusted based on regular monitoring of these parameters.

Side Effects

The most common side effects of sapropterin include headache, rhinorrhea (runny nose), and pharyngolaryngeal pain. Gastrointestinal disturbances such as diarrhea and vomiting may also occur. Most side effects are mild to moderate in severity and tend to decrease over time with continued treatment.

Pharmacokinetics

Sapropterin is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 to 4 hours. It is metabolized in the body and excreted primarily in the urine. The half-life of sapropterin varies depending on the individual, but it is generally around 6 to 8 hours, necessitating once or twice daily dosing to maintain therapeutic levels.

History

Sapropterin was approved by the Food and Drug Administration (FDA) in the United States in 2007 as the first pharmacological treatment option for PKU. Its approval provided a significant advancement in the management of PKU, offering an alternative to the strict dietary restrictions that were previously the only option for managing this condition.

Conclusion

Sapropterin represents a significant advancement in the treatment of phenylketonuria, offering hope to those affected by this genetic disorder. Its development underscores the importance of continued research and innovation in the field of rare diseases.