Possible Interaction: Tyrosine and Nitisinone

“FAH−/− rabbits exhibit phenotypic features of HT1 including liver and kidney abnormalities but additionally develop frequent ocular manifestations likely caused by local accumulation of tyrosine upon NTBC administration.”

“The high tyrosine concentrations caused by treatment with NTBC could result in ophthalmological and skin problems and requires life-long dietary restriction of tyrosine and its precursor phenylalanine, which could be strenuous to adhere to.”

“ Nitisinone inhibits the degradation of tyrosine and thereby the production of harmful metabolites, however, the concentration of tyrosine also increases.”

“ Serum tyrosine and urinary 3-MT increased significantly following treatment with nitisinone.”

“ Serum tyrosine increased at least 6-fold following nitisinone (p ≤ 0.0001, all visits), and urinary 3-methoxytyramine (3-MT) increased at 12 and 24 months (p ≤ 0.0001), and 5-hydroxyindole acetic acid (5-HIAA) decreased at 12 months (p = 0.03).”

“ Nitisinone produced an increase in tyrosine and catecholamine metabolite (HVA, VMA, and metanephrines) levels.”

“ Plasma tyrosine and homogentisic acid increased (9-fold, p = < 0.0001) and decreased (9-fold, p = 0.004), respectively in HGD−/− mice treated with nitisinone.”

“ Tyrosine (10-fold in both comparisons, p = 0.003; [BALB/c HGD−/− (n = 6) and BALB/c HGD+/− (n = 6) (no treatment) vs. BALB/c HGD−/− (n = 6, treated)] and tyramine (25-fold, p = 0.02; 32-fold, p = 0.02) increased significantly following treatment with nitisinone.”

“In laboratory animals, treatment with nitisinone leads to the elevation of plasma tyrosine (tyrosinaemia).”

“ Nitisinone effectively blocks the metabolism of tyrosine to prevent the formation of the toxic compound succinylacetone (and precursor fumarylacetoacetate) in affected children.”

“Urinary excretion of HGA decreases in a concentration-dependent manner, while the increase in tyrosine is less clearly related to nitisinone concentrations.”