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Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator’s product
BACKGROUND: Existence of anti-malarial generic drugs with low bioavailability marketed on sub-Saharan Africa raises a concern on patients achieving therapeutic concentrations after intake of such products. This work compared bioavailability of one generic tablet formulation with innovator’s product....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669611/ https://www.ncbi.nlm.nih.gov/pubmed/23718725 http://dx.doi.org/10.1186/1475-2875-12-174 |
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author | Minzi, Omary MS Marealle, Ignace A Shekalaghe, Seif Juma, Omar Ngaimisi, Eliford Chemba, Mwajuma Rutaihwa, Mastidia Abdulla, Salim Sasi, Philip |
author_facet | Minzi, Omary MS Marealle, Ignace A Shekalaghe, Seif Juma, Omar Ngaimisi, Eliford Chemba, Mwajuma Rutaihwa, Mastidia Abdulla, Salim Sasi, Philip |
author_sort | Minzi, Omary MS |
collection | PubMed |
description | BACKGROUND: Existence of anti-malarial generic drugs with low bioavailability marketed on sub-Saharan Africa raises a concern on patients achieving therapeutic concentrations after intake of such products. This work compared bioavailability of one generic tablet formulation with innovator’s product. Both were fixed dose combination tablet formulations containing artemether and lumefantrine. METHODOLOGY: The study was conducted in Dar Es Salaam, Tanzania, in which a survey of the most abundant generic containing artemether-lumefantrine tablet formulation was carried out in retail pharmacies. The most widely available generic (Artefan®, Ajanta Pharma Ltd, Maharashtra, India) was sampled for bioavailability comparison with Coartem® (Novartis Pharma, Basel, Switzerland) - the innovator’s product. A randomized, two-treatment cross-over study was conducted in 18 healthy Tanzanian black male volunteers. Each volunteer received Artefan® (test) and Coartem® (as reference) formulation separated by 42 days of drug-free washout period. Serial blood samples were collected up to 168 hours after oral administration of a single dose of each treatment. Quantitation of lumefantrine plasma levels was done using HPLC with UV detection. Bioequivalence of the two products was assessed in accordance with the US Food and Drug Authority (FDA) guidelines. RESULTS: The most widely available generic in pharmacies was Artefan® from India. All eighteen enrolled volunteers completed the study and both test and reference tablet formulations were well tolerated. It was possible to quantify lumefantrine alone, therefore, the pharmacokinetic parameters reported herein are for lumefantrine. The geometric mean ratios for C(max), AUC(0-t) and AUC(0-∞) were 84% in all cases and within FDA recommended bioequivalence limits of 80% – 125%, but the 90% confidence intervals were outside FDA recommended limits (CI 49–143%, 53 - 137%, 52 - 135% respectively). There were no statistical significant differences between the two formulations with regard to PK parameters (P > 0.05). CONCLUSIONS: Although the ratios of AUCs and C(max) were within the acceptable FDA range, bioequivalence between Artefan® and Coartem® tablet formulations was not demonstrated due to failure to comply with the FDA 90% confidence interval criteria. Based on the observed total drug exposure (AUCs), Artefan® is likely to produce a similar therapeutic response as Coartem®. |
format | Online Article Text |
id | pubmed-3669611 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36696112013-06-02 Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator’s product Minzi, Omary MS Marealle, Ignace A Shekalaghe, Seif Juma, Omar Ngaimisi, Eliford Chemba, Mwajuma Rutaihwa, Mastidia Abdulla, Salim Sasi, Philip Malar J Research BACKGROUND: Existence of anti-malarial generic drugs with low bioavailability marketed on sub-Saharan Africa raises a concern on patients achieving therapeutic concentrations after intake of such products. This work compared bioavailability of one generic tablet formulation with innovator’s product. Both were fixed dose combination tablet formulations containing artemether and lumefantrine. METHODOLOGY: The study was conducted in Dar Es Salaam, Tanzania, in which a survey of the most abundant generic containing artemether-lumefantrine tablet formulation was carried out in retail pharmacies. The most widely available generic (Artefan®, Ajanta Pharma Ltd, Maharashtra, India) was sampled for bioavailability comparison with Coartem® (Novartis Pharma, Basel, Switzerland) - the innovator’s product. A randomized, two-treatment cross-over study was conducted in 18 healthy Tanzanian black male volunteers. Each volunteer received Artefan® (test) and Coartem® (as reference) formulation separated by 42 days of drug-free washout period. Serial blood samples were collected up to 168 hours after oral administration of a single dose of each treatment. Quantitation of lumefantrine plasma levels was done using HPLC with UV detection. Bioequivalence of the two products was assessed in accordance with the US Food and Drug Authority (FDA) guidelines. RESULTS: The most widely available generic in pharmacies was Artefan® from India. All eighteen enrolled volunteers completed the study and both test and reference tablet formulations were well tolerated. It was possible to quantify lumefantrine alone, therefore, the pharmacokinetic parameters reported herein are for lumefantrine. The geometric mean ratios for C(max), AUC(0-t) and AUC(0-∞) were 84% in all cases and within FDA recommended bioequivalence limits of 80% – 125%, but the 90% confidence intervals were outside FDA recommended limits (CI 49–143%, 53 - 137%, 52 - 135% respectively). There were no statistical significant differences between the two formulations with regard to PK parameters (P > 0.05). CONCLUSIONS: Although the ratios of AUCs and C(max) were within the acceptable FDA range, bioequivalence between Artefan® and Coartem® tablet formulations was not demonstrated due to failure to comply with the FDA 90% confidence interval criteria. Based on the observed total drug exposure (AUCs), Artefan® is likely to produce a similar therapeutic response as Coartem®. BioMed Central 2013-05-30 /pmc/articles/PMC3669611/ /pubmed/23718725 http://dx.doi.org/10.1186/1475-2875-12-174 Text en Copyright © 2013 Minzi et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Minzi, Omary MS Marealle, Ignace A Shekalaghe, Seif Juma, Omar Ngaimisi, Eliford Chemba, Mwajuma Rutaihwa, Mastidia Abdulla, Salim Sasi, Philip Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator’s product |
title | Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator’s product |
title_full | Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator’s product |
title_fullStr | Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator’s product |
title_full_unstemmed | Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator’s product |
title_short | Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator’s product |
title_sort | comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the tanzanian market and the innovator’s product |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669611/ https://www.ncbi.nlm.nih.gov/pubmed/23718725 http://dx.doi.org/10.1186/1475-2875-12-174 |
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