ArticleJIMD reports2015
Relationship Between Serum Concentrations of Nitisinone and Its Effect on Homogentisic Acid and Tyrosine in Patients with Alkaptonuria.
Article in JIMD reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- Homogentisate 1,2-dioxygenase (HGD) gene variants, their analysis and genotype-phenotype correlations in the largest cohort of patients with AKU.European journal of human genetics : EJHG · 2019Trial
- A robust high-throughput screening system to assess bacterial tyrosine ammonia lyase activity in the context of tyrosine inherited metabolic disorders.Scientific reports · 2024Article
- Untargeted NMR Metabolomics Reveals Alternative Biomarkers and Pathways in Alkaptonuria.International journal of molecular sciences · 2022Article
- Metabolomic studies in the inborn error of metabolism alkaptonuria reveal new biotransformations in tyrosine metabolism.Genes & diseases · 2022Article
- Characterization of changes in the tyrosine pathway by 24-h profiling during nitisinone treatment in alkaptonuria.Molecular genetics and metabolism reports · 2022Article
- Effects of a protein-restricted diet on body weight and serum tyrosine concentrations in patients with alkaptonuria.JIMD reports · 2022Article
- Alkaptonuria: Current Perspectives.The application of clinical genetics · 2020Review
- Evaluation of the serum metabolome of patients with alkaptonuria before and after two years of treatment with nitisinone using LC-QTOF-MS.JIMD reports · 2019Article
- Assessing the effect of nitisinone induced hypertyrosinaemia on monoamine neurotransmitters in brain tissue from a murine model of alkaptonuria using mass spectrometry imaging.Metabolomics : Official journal of the Metabolomic Society · 2019Article
- Non randomized study on the potential of nitisinone to inhibit cytochrome P450 2C9, 2D6, 2E1 and the organic anion transporters OAT1 and OAT3 in healthy volunteers.European journal of clinical pharmacology · 2019Article
- Article
- Serum Amino Acid Profiling in Patients with Alkaptonuria Before and After Treatment with Nitisinone.JIMD reports · 2018Article
- Article
- Progress in Alkaptonuria--are we near to an effective therapy?Journal of inherited metabolic disease · 2015Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlkaptonuria (AKU) is a serious genetic disease due to a defect in tyrosine metabolism, leading to increased serum levels of homogentisic acid (HGA). Nitisinone decreases HGA in AKU, but the concentration-response relationship has not been previously reported.
objectivesTo determine the relationship between serum concentrations of nitisinone and the effect on both HGA and tyrosine; secondly to determine steady-state pharmacokinetics of nitisinone in AKU patients.
methodThirty-two patients with AKU received either 1, 2, 4, or 8 mg nitisinone daily. Urine and serum HGA and serum tyrosine and nitisinone were measured during 24 h at baseline (before first dose) and after 4 weeks of treatment.
resultsNitisinone pharmacokinetics (area under the curve [AUC] and maximum concentrations [C max]) were dose proportional. The median oral clearance determined in all patients, irrespective of dose, was 3.18 mL/h·kg (range 1.6-6.7).Nitisinone decreased urinary excretion of HGA in a concentration-dependent manner, with a maximum effect seen at average nitisinone concentrations of 3 μmol/L. The association between nitisinone and tyrosine concentrations was less pronounced. Serum levels of HGA at Week 4 were below the limit of quantitation in 65% of samples, which prevented determination of the relationship with nitisinone concentrations.
conclusionNitisinone exhibits dose-proportional pharmacokinetics in the studied dosage interval. Urinary excretion of HGA decreases in a concentration-dependent manner, while the increase in tyrosine is less clearly related to nitisinone concentrations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.