Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers

Karen Thudium,1 Jorge Gallo,2 Emmanuel Bouillaud,2 Carolin Sachs,2 Simantini Eddy,1 Wing Cheung1 1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2Novartis Pharma AG, Basel, Switzerland Background: The mammalian target of rapamycin (mTOR) inhibitor everolimus has a well-established ph...

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Autores principales:	Thudium K, Gallo J, Bouillaud E, Sachs C, Eddy S, Cheung W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/a9a406de6a644a77b6c7588a9bda3a0f
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spelling	oai:doaj.org-article:a9a406de6a644a77b6c7588a9bda3a0f2021-12-02T04:24:58ZBioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers1179-1438https://doaj.org/article/a9a406de6a644a77b6c7588a9bda3a0f2015-01-01T00:00:00Zhttp://www.dovepress.com/bioavailability-of-everolimus-administered-as-a-single-5-mg-tablet-ver-peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438 Karen Thudium,1 Jorge Gallo,2 Emmanuel Bouillaud,2 Carolin Sachs,2 Simantini Eddy,1 Wing Cheung1 1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2Novartis Pharma AG, Basel, Switzerland Background: The mammalian target of rapamycin (mTOR) inhibitor everolimus has a well-established pharmacokinetics profile. We conducted a randomized, single-center, open-label, two-sequence, two-period crossover study of healthy volunteers to assess the relative bioavailability of everolimus administered as one 5 mg tablet or five 1 mg tablets. Methods: Subjects were randomized 1:1 to receive everolimus dosed as one 5 mg tablet or as five 1 mg tablets on day 1, followed by a washout period on days 8–14 and then the opposite formulation on day 15. Blood sampling for pharmacokinetic evaluation was performed at prespecified time points, with 17 samples taken for each treatment period. Primary variables for evaluation of relative bioavailability were area under the concentration–time curve from time zero to infinity (AUCinf) and maximum blood concentration (Cmax). Safety was assessed by reporting the incidence of adverse events (AEs). Results: Twenty-two participants received everolimus as one 5 mg tablet followed by five 1 mg tablets (n=11) or the opposite sequence (n=11). The Cmax of five 1 mg tablets was 48% higher than that of one 5 mg tablet (geometric mean ratio, 1.48; 90% confidence interval [CI], 1.35–1.62). AUCinf was similar (geometric mean ratio, 1.08; 90% CI, 1.02–1.16), as were the extent of absorption and the distribution and elimination kinetics. AEs, all grade 1 or 2, were observed in 54.5% of subjects. Conclusion: Although the extent of absorption was similar, the Cmax of five 1 mg tablets was higher than that of one 5 mg tablet, suggesting these formulations lead to different peak blood concentrations and are not interchangeable at the dose tested. Keywords: absorption kinetics, healthy volunteersThudium KGallo JBouillaud ESachs CEddy SCheung WDove Medical PressarticleTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol 2015, Iss default, Pp 11-17 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 Thudium K Gallo J Bouillaud E Sachs C Eddy S Cheung W Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers
description	Karen Thudium,1 Jorge Gallo,2 Emmanuel Bouillaud,2 Carolin Sachs,2 Simantini Eddy,1 Wing Cheung1 1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2Novartis Pharma AG, Basel, Switzerland Background: The mammalian target of rapamycin (mTOR) inhibitor everolimus has a well-established pharmacokinetics profile. We conducted a randomized, single-center, open-label, two-sequence, two-period crossover study of healthy volunteers to assess the relative bioavailability of everolimus administered as one 5 mg tablet or five 1 mg tablets. Methods: Subjects were randomized 1:1 to receive everolimus dosed as one 5 mg tablet or as five 1 mg tablets on day 1, followed by a washout period on days 8–14 and then the opposite formulation on day 15. Blood sampling for pharmacokinetic evaluation was performed at prespecified time points, with 17 samples taken for each treatment period. Primary variables for evaluation of relative bioavailability were area under the concentration–time curve from time zero to infinity (AUCinf) and maximum blood concentration (Cmax). Safety was assessed by reporting the incidence of adverse events (AEs). Results: Twenty-two participants received everolimus as one 5 mg tablet followed by five 1 mg tablets (n=11) or the opposite sequence (n=11). The Cmax of five 1 mg tablets was 48% higher than that of one 5 mg tablet (geometric mean ratio, 1.48; 90% confidence interval [CI], 1.35–1.62). AUCinf was similar (geometric mean ratio, 1.08; 90% CI, 1.02–1.16), as were the extent of absorption and the distribution and elimination kinetics. AEs, all grade 1 or 2, were observed in 54.5% of subjects. Conclusion: Although the extent of absorption was similar, the Cmax of five 1 mg tablets was higher than that of one 5 mg tablet, suggesting these formulations lead to different peak blood concentrations and are not interchangeable at the dose tested. Keywords: absorption kinetics, healthy volunteers
format	article
author	Thudium K Gallo J Bouillaud E Sachs C Eddy S Cheung W
author_facet	Thudium K Gallo J Bouillaud E Sachs C Eddy S Cheung W
author_sort	Thudium K
title	Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers
title_short	Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers
title_full	Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers
title_fullStr	Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers
title_full_unstemmed	Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers
title_sort	bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/a9a406de6a644a77b6c7588a9bda3a0f
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Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers

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