Validation of a Therapeutic Range for Nitisinone in Patients Treated for Tyrosinemia Type 1 Based on Reduction of Succinylacetone Excretion

Overview

Journal JIMD Rep

Publisher Wiley

Date 2019 Jun 27

PMID 31240158

Citations 5

Authors

Rhona M Jack

C Ronald Scott

Affiliations

Soon will be listed here.

Abstract

The drug nitisinone (NTBC; Orfadin, Vienna, Austria) has been used for the treatment of hereditary tyrosinemia type-1 since 1991. Nitisinone effectively blocks the metabolism of tyrosine to prevent the formation of the toxic compound succinylacetone (and precursor fumarylacetoacetate) in affected children. Monitoring of plasma drug levels and urine succinylacetone can be used to assess compliance and adequate dose of drug. We present retrospective data from patient monitoring for over 10 years that provide validation of a target therapeutic range for nitisinone of 40 to 60 μmol/L. The target nitisinone range is justified as valid based on reduction of succinylacetone excretion. There was no statistical significance in succinylacetone excretion in mmol/mol creatinine above a level of 40 μmol/L plasma NTBC ( > 0.05).

Citing Articles

NTBC Treatment Monitoring in Chilean Patients with Tyrosinemia Type 1 and Its Association with Biochemical Parameters and Liver Biomarkers.

Fuenzalida K, Leal-Witt M, Guerrero P, Hamilton V, Salazar M, Penaloza F J Clin Med. 2021; 10(24).

PMID: 34945128 PMC: 8706240. DOI: 10.3390/jcm10245832.

Physical Growth of Patients with Hereditary Tyrosinaemia Type I: A Single-Centre Retrospective Study.

Yilmaz O, Daly A, Pinto A, Ashmore C, Evans S, Gupte G Nutrients. 2021; 13(9).

PMID: 34578949 PMC: 8472760. DOI: 10.3390/nu13093070.

Therapeutic Targeting of Fumaryl Acetoacetate Hydrolase in Hereditary Tyrosinemia Type I.

Gil-Martinez J, Macias I, Unione L, Bernardo-Seisdedos G, Lopitz-Otsoa F, Fernandez-Ramos D Int J Mol Sci. 2021; 22(4).

PMID: 33670179 PMC: 7916972. DOI: 10.3390/ijms22041789.

Type 1 tyrosinemia in Finland: a nationwide study.

Aarela L, Hiltunen P, Soini T, Vuorela N, Huhtala H, Nevalainen P Orphanet J Rare Dis. 2020; 15(1):281.

PMID: 33046095 PMC: 7549233. DOI: 10.1186/s13023-020-01547-w.

Validation of a therapeutic range for nitisinone in patients treated for tyrosinemia type 1 based on reduction of succinylacetone excretion.

Jack R, Scott C JIMD Rep. 2019; 46(1):75-78.

PMID: 31240158 PMC: 6498826. DOI: 10.1002/jmd2.12023.

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