Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects
Abstract Background Efforts to ease administration and enhance acceptability of the oral anti-malarial artemether-lumefantrine (A-L) crushed tablet to infants and children triggered the development of a novel dispersible tablet of A-L. During early development of this new formulation, two studies we...
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ftdoajarticles:oai:doaj.org/article:d67c4763425448c4863de339d9b90638 2023-05-15T15:15:38+02:00 Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects Abdulla Salim Amuri Baraka Kabanywanyi Abdunoor M Ubben David Reynolds Christine Pascoe Steve Fitoussi Serge Yeh Ching-Ming Nuortti Marja Séchaud Romain Kaiser Günther Lefèvre Gilbert 2010-09-01T00:00:00Z https://doi.org/10.1186/1475-2875-9-253 https://doaj.org/article/d67c4763425448c4863de339d9b90638 EN eng BMC http://www.malariajournal.com/content/9/1/253 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-253 1475-2875 https://doaj.org/article/d67c4763425448c4863de339d9b90638 Malaria Journal, Vol 9, Iss 1, p 253 (2010) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2010 ftdoajarticles https://doi.org/10.1186/1475-2875-9-253 2022-12-31T13:08:57Z Abstract Background Efforts to ease administration and enhance acceptability of the oral anti-malarial artemether-lumefantrine (A-L) crushed tablet to infants and children triggered the development of a novel dispersible tablet of A-L. During early development of this new formulation, two studies were performed in healthy subjects, one to evaluate the palatability of three flavours of A-L, and a second one to compare the bioavailability of active principles between the dispersible tablet and the tablet (administered crushed and intact). Methods Study 1 was performed in 48 healthy schoolchildren in Tanzania. Within 1 day, all subjects tasted a strawberry-, orange- and cherry-flavoured oral A-L suspension for 10 seconds (without swallowing) in a randomized, single-blind, crossover fashion. The palatability of each formulation was rated using a visual analogue scale (VAS). Study 2 was an open, randomized crossover trial in 48 healthy adults given single doses of A-L (80 mg artemether + 480 mg lumefantrine) with food. The objectives were to compare the bioavailability of artemether, dihydroartemisinin (DHA) and lumefantrine between the dispersible tablet and the tablet administered crushed (primary objective) and intact (secondary objective). Results Study 1 showed no statistically significant difference in VAS scores between the three flavours but cherry had the highest score in several ratings (particularly for overall liking). Study 2 demonstrated that the dispersible and crushed tablets delivered bioequivalent artemether, DHA and lumefantrine systemic exposure (area under the curve [AUC]); mean ± SD AUC 0-tlast were 208 ± 113 vs 195 ± 93 h.ng/ml for artemether, 206 ± 81 vs 199 ± 84 h.ng/ml for DHA and 262 ± 107 vs 291 ± 106 h.μg/ml for lumefantrine. Bioequivalence was also shown for peak plasma concentrations (C max ) of DHA and lumefantrine. Compared with the intact tablet, the dispersible tablet resulted in bioequivalent lumefantrine exposure, but AUC and C max values of artemether and DHA were 20-35% lower. ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 9 1 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Abdulla Salim Amuri Baraka Kabanywanyi Abdunoor M Ubben David Reynolds Christine Pascoe Steve Fitoussi Serge Yeh Ching-Ming Nuortti Marja Séchaud Romain Kaiser Günther Lefèvre Gilbert Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Efforts to ease administration and enhance acceptability of the oral anti-malarial artemether-lumefantrine (A-L) crushed tablet to infants and children triggered the development of a novel dispersible tablet of A-L. During early development of this new formulation, two studies were performed in healthy subjects, one to evaluate the palatability of three flavours of A-L, and a second one to compare the bioavailability of active principles between the dispersible tablet and the tablet (administered crushed and intact). Methods Study 1 was performed in 48 healthy schoolchildren in Tanzania. Within 1 day, all subjects tasted a strawberry-, orange- and cherry-flavoured oral A-L suspension for 10 seconds (without swallowing) in a randomized, single-blind, crossover fashion. The palatability of each formulation was rated using a visual analogue scale (VAS). Study 2 was an open, randomized crossover trial in 48 healthy adults given single doses of A-L (80 mg artemether + 480 mg lumefantrine) with food. The objectives were to compare the bioavailability of artemether, dihydroartemisinin (DHA) and lumefantrine between the dispersible tablet and the tablet administered crushed (primary objective) and intact (secondary objective). Results Study 1 showed no statistically significant difference in VAS scores between the three flavours but cherry had the highest score in several ratings (particularly for overall liking). Study 2 demonstrated that the dispersible and crushed tablets delivered bioequivalent artemether, DHA and lumefantrine systemic exposure (area under the curve [AUC]); mean ± SD AUC 0-tlast were 208 ± 113 vs 195 ± 93 h.ng/ml for artemether, 206 ± 81 vs 199 ± 84 h.ng/ml for DHA and 262 ± 107 vs 291 ± 106 h.μg/ml for lumefantrine. Bioequivalence was also shown for peak plasma concentrations (C max ) of DHA and lumefantrine. Compared with the intact tablet, the dispersible tablet resulted in bioequivalent lumefantrine exposure, but AUC and C max values of artemether and DHA were 20-35% lower. ... |
format |
Article in Journal/Newspaper |
author |
Abdulla Salim Amuri Baraka Kabanywanyi Abdunoor M Ubben David Reynolds Christine Pascoe Steve Fitoussi Serge Yeh Ching-Ming Nuortti Marja Séchaud Romain Kaiser Günther Lefèvre Gilbert |
author_facet |
Abdulla Salim Amuri Baraka Kabanywanyi Abdunoor M Ubben David Reynolds Christine Pascoe Steve Fitoussi Serge Yeh Ching-Ming Nuortti Marja Séchaud Romain Kaiser Günther Lefèvre Gilbert |
author_sort |
Abdulla Salim |
title |
Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects |
title_short |
Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects |
title_full |
Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects |
title_fullStr |
Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects |
title_full_unstemmed |
Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects |
title_sort |
early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects |
publisher |
BMC |
publishDate |
2010 |
url |
https://doi.org/10.1186/1475-2875-9-253 https://doaj.org/article/d67c4763425448c4863de339d9b90638 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 9, Iss 1, p 253 (2010) |
op_relation |
http://www.malariajournal.com/content/9/1/253 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-253 1475-2875 https://doaj.org/article/d67c4763425448c4863de339d9b90638 |
op_doi |
https://doi.org/10.1186/1475-2875-9-253 |
container_title |
Malaria Journal |
container_volume |
9 |
container_issue |
1 |
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1766345994400694272 |