Comparative study of pharmacokinetics and bioequivalence of preparations containing nitisinone: Nitisinone, capsules 10 mg (ZAO Obninsk Chemical-Pharmaceutical Company (ZAO OCPC), Russia) and Orfadin®, capsules 10 mg (“Apotek Production and Laboratory AB”, Sweden) with a single capsule taken on an empty stomach by healthy volunteers. An open randomized cross-examination included 36 healthy volunteers. As a novel strategy the drugs (the test and the comparison drug) were administered once, followed by blood sampling for 72 hours. The “washout” period between study periods was 14 days. Nitisinone concentration in blood plasma samples was quantitatively determined by high-performance liquid chromatography with tandem mass spectrometry (HPLC/MS). The boundaries of the estimated 90% confidence intervals for the ratios of the mean values of the analyzed parameters (Cmax, AUC0-72) are within 80-125% according to the existing guidelines. Nitisinone is bioequivalent to Orfadin. Comparable drugs were also comparable in safety indicators.


  • Das AM (2017) Clinical utility of nitisinone for the treatment of hereditary tyrosinemia type-1 (HT-1). The application of clinical genetics journal 10: 43-48.
  • El-Hamady, M. M. (2017). Growth and Yield of Onion Alum cepa L. as Influenced by Nitrogen and Phosphorus Fertilizers Levels. Canadian Journal of Agriculture and Crops, 2(1), 34-41.
  • Holme E, Lindstedt S (2000) Nontransplant treatment of tyrosinemia. Clinics in liver disease Journal 4(4): 805-814.
  • Hughes JH, Wilson PJ, Sutherland H, Judd S, Hughes AT, Milan AM, et al. (2019) Dietary restriction of tyrosine and phenylalanine lowers tyrosinaemia associated with nitisinone therapy of alkaptonuria. Journal of inherited metabolic disease 1: 1-10.
  • Keenan CM, Preston AJ, Sutherland H, Wilson PJ, Psarelli EE, Cox TF, et al. (2015) Nitisinone arrests but does not reverse ochronosis in alkaptonuric mice. JIMD Reports 24: 45-50.
  • King LS, Trahms C, Scott CR (2017) Tyrosinemia type I. GeneReviews Journal 34: 677-687.
  • McKiernan PJ (2013) Nitisinone for the treatment of hereditary tyrosinemia type I. Expert Opinion on Orphan Drugs 1(6): 491-497.
  • Mironova AN (2013) Guidelines for the Use of Medicines. Moscow: Russia, Grif publishing house (in Russian)
  • Mitchell G, Grompe M, Lambert M, Тanguay M (2001) Hypertyrosinemia. The metabolic and molecular bases of inherited disease. New-York: McGraw-Hill Publication.
  • Ranganath LR, Khedr M, Milan AM, Davison AS, Hughes AT, Usher JL, et al. (2018) Nitisinone arrests ochronosis and decreases rate of progression of alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre. Molecular genetics and metabolism journal 125(1-2): 127-134.
  • Ranganath LR, Milan AM, Hughes AT, Dutton JJ, Fitzgerald R, Briggs MC, et al. (2016) Suitability of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment. Annals of the rheumatic diseases journal 75(2): 362-367.
  • Shahamat S, Alishahi M, Banaee M, Shahriali A (2015) Effects of Sub-lethal Concentrations of Atrazine on Some Oxidative Stress Biomarker in Various Tissues of Grass Carp (Ctenopharyngodon idella). Journal of Environmental Treatment Techniques, 3(1): 1-6.
  • Simoncelli M, Samson J, Bussières JF, Lacroix J, Dorais M, Battista R, Perreault S (2015) Cost–consequence analysis of nitisinone for treatment of tyrosinemia type I. The Canadian journal of hospital pharmacy 68(3): 210-234.
  • Sloboda N, Wiedemann A, Merten M, Alqahtani A, Jeannesson E, Blum A, et al. (2019) Efficacy of low dose nitisinone in the management of alkaptonuria. Molecular Genetics and Metabolism journal 127(3): 184-190.
  • Taylor AM, Shepherd L (2019) The potential of nitisinone for the treatment of alkaptonuria. Expert Opinion on Orphan Drugs 7(10): 435-441.
  • Van Spronsen FJ, Thomasse Y, Smit GPA, Leonard JV, Clayton PT, Fidler V, et al. (1994) Hereditary tyrosinemia type I: a new clinical classification with difference in prognosis on dietary treatment. Hepatology Journal 20(5): 1187-1191.


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