6-lactoyl-5,6,7,8-tetrahydropterin

Tetrahydrobiopterin

Clinical data
License data	US FDA: Kuvan
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	By mouth
ATC code	A16AX07 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Biological half-life	4 hours (healthy adults) 6–7 hours (PKU patients)
Identifiers
IUPAC name (6R)-2-Amino-6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydropteridin-4(1H)-one
CAS Number	17528-72-2 Y
PubChem CID	44257
IUPHAR/BPS	5276
DrugBank	DB00360 Y
ChemSpider	40270 Y
ChEBI	CHEBI:59560 Y
ChEMBL	CHEMBL1201774 N
Chemical and physical data
Formula	C9H15N5O3
Molar mass	241.25 g/mol
3D model (JSmol)	Interactive image
SMILES O=C2\N=C(/NC=1NC[C@@H](NC=12)[C@@H](O)[C@@H](O)C)N
InChI InChI=1S/C9H15N5O3/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7/h3-4,6,12,15-16H,2H2,1H3,(H4,10,11,13,14,17)/t3-,4+,6-/m0/s1 Y Key:FNKQXYHWGSIFBK-RPDRRWSUSA-N Y
NY (what is this?)

Tetrahydrobiopterin (BH₄, THB), also known as sapropterin, is a naturally occurring essential cofactor of the three aromatic amino acid hydroxylase enzymes, used in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT), melatonin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and is a cofactor for the production of nitric oxide (NO) by the nitric oxide synthases. Chemically, its structure is that of a reduced pteridine derivative.

Tetrahydrobiopterin is available as a tablet for oral administration in the form of tetrahydrobiopterin dihydrochloride (BH4*2HCL). BH4*2HCL is FDA approved under the trade name Kuvan. The typical cost of treating a patient with Kuvan is $100,000 per year.BioMarin holds the patent for Kuvan until at least 2024, but Par Pharmaceutical has a right to produce a generic version by 2020.

BH4*2HCL is indicated in tetrahydrobiopterin deficiency caused by GTPCH deficiency or PTPS deficiency. Also, BH4*2HCL is FDA approved for use in phenylketonuria, along with dietary measures. Most people with phenylketonuria, however, have little or no benefit of BH4*2HCL.

The most common adverse effects, observed in more than 10% of patients, include headache and a running or obstructed nose. Diarrhea and vomiting are also relatively common, seen in at least 1% of patients.

No interaction studies have been conducted. Because of its mechanism, tetrahydrobiopterin might interact with dihydrofolate reductase inhibitors like methotrexate and trimethoprim, and NO-enhancing drugs like nitroglycerin, molsidomine, minoxidil, and PDE5 inhibitors. Combination of tetrahydrobiopterin with levodopa can lead to increased excitability.