Bioequivalence of two oral formulations of nitazoxanide in healthy volunteers
DOI:
https://doi.org/10.30968/rbfhss.2024.153.1106Abstract
Objective: This study evaluated the bioequivalence (BE) between two Nitazoxanide 20mg/ml oral suspension formulations. Methods: We carried out a single-center, open-label, randomized, single-dose, two-sequence, two-period. Subjects received single oral doses of 500 mg Nitazoxanide oral suspension. Whole blood samples were collected pre-dose and at specified intervals up to 12 h post-dose to assess pharmacokinetic parameters. Results: Thirty healthy adult subjects completed the study. We found the 90% confidence intervals for the geometric mean ratios for the Tixozanide area under the curve AUC0‐t and AUC0‐∞ and maximum plasma concentration (Cmax) were within the established limits of 80% to 125 % of BE. Conclusion: The criteria for BE were met for the nitazoxanide formulations from Eurofarma Laboratórios S.A.
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References
White CA, Jr. Nitazoxanide: a new broad spectrum antiparasitic agent. Expert Rev Anti Infect Ther. 2004;2(1):43-9. doi: 10.1586/14787210.2.1.43.
ANVISA. Lista A de Medicamentos de Referência 2013 [cited 2013/2022 04/07/2022]. Available from: https://www.gov.br/anvisa/pt-br/setorregulado/regularizacao/medicamentos/medicamentos-de-referencia/lista-de-medicamentos-dereferencia.
Firake BM, Chettiar R, Firake TB, editors. Nitazoxanide: A Review of Analytical Methods2017.
Lokhande AS, Devarajan PV. A review on possible mechanistic insights of Nitazoxanide for repurposing in COVID-19. Eur J Pharmacol. 2021;891:173748. Epub 2020/11/24. doi: 10.1016/j.ejphar.2020.173748.
Rossignol JF. Nitazoxanide: a first-in-class broad-spectrum antiviral agent. Antiviral Res. 2014;110:94-103. Epub 2014/08/12. doi: 10.1016/j.antiviral.2014.07.014. PubMed PMID: 25108173;
Broekhuysen J, Stockis A, Lins RL, De Graeve J, Rossignol JF. Nitazoxanide: pharmacokinetics and metabolism in man. Int J Clin Pharmacol Ther. 2000;38(8):387-94. Epub 2000/09/13. doi: 10.5414/cpp38387.
ROMARK-PHARMACEUTICALS. Alinia® (nitazoxanide) Tablets: Prescribing Information.
Rossignol JF, Santoro MG, editors. Activity of thiazolides against other respiratory viruses than influenza. Third ISIRV Antiviral Group Conference; 2014 4–6 June 2014; Tokio, Japan Tokio, Japan2014.
Chopra D, Boparai JK, Bhandari B, Srivastava A, Gupta R. Pharmacological Strategies for COVID-19 - A Review of the Most Promising Repurposed Antiviral Drugs. Infect Disord Drug Targets. 2021;21(7):e160921189260. doi: 10.2174/1871526520666201218151841.
Mule S, Singh A, Greish K, Sahebkar A, Kesharwani P, Shukla R. Drug repurposing strategies and key challenges for COVID-19 management. J Drug Target. 2022;30(4):413-29. doi: 10.1080/1061186x.2021.2013852.
ANVISA. Agência Nacional de Vigilância Sanitária. Lista 2 – Analito para Estabelecimento da Biodisponibilidade Relativa/Bioequivalência. 2013 [cited 2013/2022 07/06/2022]. Available from: https://www.gov.br/anvisa/pt-br/setorregulado/regularizacao/medicamentos/equivalencia-terapeutica/bioequivalencia/listas.
Agência Nacional de Vigilância Sanitária. RESOLUÇÃO - RDC Nº 27, DE 17 DE MAIO DE 2012. Dispõe sobre os requisitos mínimos para a validação de métodos bioanalíticos empregados em estudos com fins de registro e pós-registro de medicamentos., (2012).
Marcelín-Jiménez G, Contreras-Zavala L, Maggi-Castellanos M, Angeles-Moreno AP, García-González A. Development of a method by UPLC-MS/MS for the quantification of tizoxanide in human plasma and its pharmacokinetic application. Bioanalysis. 2012;4(8):909-17 doi: 10.4155/bio.12.41.
Gupta A, Tulsankar SL, Bhatta RS, Misra A. Pharmacokinetics, Metabolism, and Partial Biodistribution of “Pincer Therapeutic” Nitazoxanide in Mice following Pulmonary Delivery of Inhalable Particles. Molecular Pharmaceutics. 2017;14(4):1204-11. doi: 10.1021/acs.molpharmaceut.6b01089.
Liu J, Meng F, Li Z, Yu L, Peng S, Guo J, et al. Simultaneous quantification of tizoxanide and tizoxanide glucuronide in mouse plasma by liquid chromatography–tandem mass spectrometry. Biomedical Chromatography. 2016;30(11):1744-9. doi: 10.1002/bmc.3748.
Neary M, Arshad U, Tatham L, Pertinez H, Box H, Rajoli RKR, et al. Quantitation of tizoxanide in multiple matrices to Support cell culture, animal and human research. J Chromatography B. 2023;1228:123823. doi: 10.1016/j.jchromb.2023.123823.
Zhao Z, Zhang L, Xue F, Zhang T. Metabolic Profile of Nitazoxanide in Goat Feces. Chromatographia. 2008;68(9):731-8. doi: 10.1365/s10337-008-0769-1.
Agência Nacional de Vigilância Sanitária. RESOLUÇÃO-RE nº 1.170, DE 19 DE ABRIL DE 2006, (2006).
Agarwal S, Solomon WD, Gowda KV, Selvan PS, Ghosh D, Sarkar AK, et al. Bioequivalence study of a fixed dose combination of nitazoxanide and ofloxacin in Indian healthy volunteers. Arzneimittelforschung. 2007;57(10):679-83. Epub 2007/12/14. doi: 10.1055/s-0031-1296667. PubMed PMID: 18074762.
Zhang C, Liang R, Liu D, Wang X, Yang S, Hu Q, et al. Pharmacokinetics of Nitazoxanide Dry Suspensions After Single Oral Doses in Healthy Subjects: Food Effects Evaluation and Bioequivalence Study. Clin Pharmacol Drug Develop. 2024;13(7):748-54. doi: 10.1002/cpdd.1402.
Balderas-Acata JI. Bioavailability of Two Oral-Suspension Formulations of a Single Dose of Nitazoxanide 500 mg: An Open-Label, Randomized-Sequence, Two-Period Crossover, Comparison in Healthy Fasted Mexican Adult Volunteers. Journal of Bioequivalence & Bioavailability. 2011;3(3). doi: 10.4172/jbb.1000056.
Davit BM, Nwakama PE, Buehler GJ, Conner DP, Haidar SH, Patel DT, et al. Comparing Generic and Innovator Drugs: A Review of 12 Years of Bioequivalence Data from the United States Food and Drug Administration. Ann Pharmacother. 2009;43(10):1583-97. doi: 10.1345/aph.1M141.
Stockis A, De Bruyn S, Gengler C, Rosillon D. Nitazoxanide pharmacokinetics and tolerability in man during 7 days dosing with 0.5 g and 1 g b.i.d. Int J Clin Pharmacol Ther. 2002;40(5):221‐7. doi: 10.5414/cpp40221.
Paranhos J, Mercadante E, Hasenclever L. [The cost to the Brazilian Unified National Health System of the extension of drug patent terms]. Cad Saude Publica. 2020;36(11):e00169719. doi: 10.1590/0102-311x00169719.
Midha KK, McKay G. Bioequivalence; its history, practice, and future. Aaps j. 2009;11(4):664-70. doi: 10.1208/s12248-009-9142-z.
van Gelder T, Gabardi S. Methods, strengths, weaknesses, and limitations of bioequivalence tests with special regard to immunosuppressive drugs. Transpl Int. 2013;26(8):771-7. doi: 10.1111/tri.12074.
European Medicines Agency. Guideline on the investigation of bioequivalence (Rev.1), (2010).
Midha KK, Rawson MJ, Hubbard JW. The bioequivalence of highly variable drugs and drug products. Int J Clin Pharmacol Ther. 2005;43(10)
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