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Bioequivalence of two tacrolimus 1-mg formulations under fasting conditions in healthy subjects: A randomized, two-period crossover trial

Objective: The present study compared the pharmacokinetics of two (1 mg) tacrolimus formulations (test (generic from Panacea) and reference (innovator from Astellas)) after a single-dose administration as per the European Medicine Agency (EMA) guidelines to grant marketing authorization. Materials a...

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Autores principales: Mohanty, Lalitendu, Bhushan, Sumit, Rüttger, Bernd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dustri-Verlag Dr. Karl Feistle 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041308/
https://www.ncbi.nlm.nih.gov/pubmed/31841106
http://dx.doi.org/10.5414/CP203534
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author Mohanty, Lalitendu
Bhushan, Sumit
Rüttger, Bernd
author_facet Mohanty, Lalitendu
Bhushan, Sumit
Rüttger, Bernd
author_sort Mohanty, Lalitendu
collection PubMed
description Objective: The present study compared the pharmacokinetics of two (1 mg) tacrolimus formulations (test (generic from Panacea) and reference (innovator from Astellas)) after a single-dose administration as per the European Medicine Agency (EMA) guidelines to grant marketing authorization. Materials and methods: This study was a randomized, open-label, balanced, two-treatment, two-period, two-sequences, single-dose, truncated-area, crossover design with a washout period of 19 days between the phases. Healthy subjects aged 18 – 45 years (both inclusive) were included. Eligible subjects received a single oral dose of 5 × 1-mg capsule of tacrolimus either test or reference formulation. Blood samples were collected until 72.00 hours postdose, and peak concentration (C(max)) and area under the curve (AUC(0–72)) were evaluated in whole blood using validated LC-MS/MS. Safety was also assessed in each period. Results: Of 56 subjects enrolled, 52 completed both study periods. The arithmetic mean (SD) C(max) for the reference and test formulations was 40.62 (11.30) and 46.20 (10.73) ng/mL, and AUC(0–72) was 348.34 (156.41) and 361.04 (158.71) ng×h/mL, respectively. The geometric least square mean ratio (90% confidence interval (CI)) was 115.07% (90% CI: 109.81, 120.59) for C(max) and 103.78 (90% CI: 97.40, 110.58) for AUC(0–72), which fell within the acceptance range as per EMA guidelines for narrow therapeutic index drugs (C(max): 80.00 – 125.00%; AUC: 90.00 – 111.11%). No serious adverse event was observed. Conclusion: The generic tacrolimus was bioequivalent to the reference formulation, was well tolerated, and provides a well-acceptable alternative to the reference drug. Switching treatment to generic tacrolimus medication may reduce the cost and economic burden of treating transplanted patients.
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spelling pubmed-70413082020-03-13 Bioequivalence of two tacrolimus 1-mg formulations under fasting conditions in healthy subjects: A randomized, two-period crossover trial Mohanty, Lalitendu Bhushan, Sumit Rüttger, Bernd Int J Clin Pharmacol Ther Research Article Objective: The present study compared the pharmacokinetics of two (1 mg) tacrolimus formulations (test (generic from Panacea) and reference (innovator from Astellas)) after a single-dose administration as per the European Medicine Agency (EMA) guidelines to grant marketing authorization. Materials and methods: This study was a randomized, open-label, balanced, two-treatment, two-period, two-sequences, single-dose, truncated-area, crossover design with a washout period of 19 days between the phases. Healthy subjects aged 18 – 45 years (both inclusive) were included. Eligible subjects received a single oral dose of 5 × 1-mg capsule of tacrolimus either test or reference formulation. Blood samples were collected until 72.00 hours postdose, and peak concentration (C(max)) and area under the curve (AUC(0–72)) were evaluated in whole blood using validated LC-MS/MS. Safety was also assessed in each period. Results: Of 56 subjects enrolled, 52 completed both study periods. The arithmetic mean (SD) C(max) for the reference and test formulations was 40.62 (11.30) and 46.20 (10.73) ng/mL, and AUC(0–72) was 348.34 (156.41) and 361.04 (158.71) ng×h/mL, respectively. The geometric least square mean ratio (90% confidence interval (CI)) was 115.07% (90% CI: 109.81, 120.59) for C(max) and 103.78 (90% CI: 97.40, 110.58) for AUC(0–72), which fell within the acceptance range as per EMA guidelines for narrow therapeutic index drugs (C(max): 80.00 – 125.00%; AUC: 90.00 – 111.11%). No serious adverse event was observed. Conclusion: The generic tacrolimus was bioequivalent to the reference formulation, was well tolerated, and provides a well-acceptable alternative to the reference drug. Switching treatment to generic tacrolimus medication may reduce the cost and economic burden of treating transplanted patients. Dustri-Verlag Dr. Karl Feistle 2020-03 2019-12-16 /pmc/articles/PMC7041308/ /pubmed/31841106 http://dx.doi.org/10.5414/CP203534 Text en © Dustri-Verlag Dr. K. Feistle http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mohanty, Lalitendu
Bhushan, Sumit
Rüttger, Bernd
Bioequivalence of two tacrolimus 1-mg formulations under fasting conditions in healthy subjects: A randomized, two-period crossover trial
title Bioequivalence of two tacrolimus 1-mg formulations under fasting conditions in healthy subjects: A randomized, two-period crossover trial
title_full Bioequivalence of two tacrolimus 1-mg formulations under fasting conditions in healthy subjects: A randomized, two-period crossover trial
title_fullStr Bioequivalence of two tacrolimus 1-mg formulations under fasting conditions in healthy subjects: A randomized, two-period crossover trial
title_full_unstemmed Bioequivalence of two tacrolimus 1-mg formulations under fasting conditions in healthy subjects: A randomized, two-period crossover trial
title_short Bioequivalence of two tacrolimus 1-mg formulations under fasting conditions in healthy subjects: A randomized, two-period crossover trial
title_sort bioequivalence of two tacrolimus 1-mg formulations under fasting conditions in healthy subjects: a randomized, two-period crossover trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041308/
https://www.ncbi.nlm.nih.gov/pubmed/31841106
http://dx.doi.org/10.5414/CP203534
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