What is Nitisinone?

Used for treatment of

1. Hereditary Tyrosinemia Type 1 (HT-1)
2. Alkaptonuria ( Less useful)

Hereditary tyrosinemia type 1 occurs due to a deficiency in fumarylacetoacetase (FAH), the
final enzyme in the tyrosine catabolic pathway.


Mechanism of Action of Nitisinone

Nitisinone is a competitive inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase, an enzyme
upstream of FAH in the tyrosine catabolic pathway . By inhibiting the normal
catabolism of tyrosine in patients with HT-1, nitisinone prevents the accumulation of the
catabolic intermediates maleylacetoacetate and fumarylacetoacetate. In patients with HT-1,
these catabolic intermediates are converted to the toxic metabolites succinylacetone and
succinylacetoacetate, which are responsible for the observed liver and kidney toxicity.
Succinylacetone can also inhibit the porphyrin synthesis pathway leading to the accumulation
of 5-aminolevulinate, a neurotoxin responsible for the porphyric crises characteristic of HT-1.

Since nitisinone inhibits catabolism of tyrosine, use of this drug can result in elevated
plasma levels of this amino acid. Treatment with nitisinone, therefore, requires
restriction of the dietary intake of tyrosine and phenylalanine to prevent the toxicity
associated with elevated plasma levels of tyrosine



Link : More information of Nitisinone at FDA page