Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine
INTRODUCTION: Gln‐1062 (MEMOGAIN) is an intranasally administered lipophilic prodrug of galantamine. Based on high brain‐to‐blood concentrations observed in pre‐clinical studies, Gln‐1062 is expected to have superior cognitive efficacy compared to oral galantamine. METHODS: Forty‐eight healthy elder...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551138/ https://www.ncbi.nlm.nih.gov/pubmed/33083515 http://dx.doi.org/10.1002/trc2.12093 |
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author | Bakker, Charlotte van der Aart, Jasper Hart, Ellen P. Klaassen, Erica S. Bergmann, Kirsten R. van Esdonk, Michiel J. Kay, Denis G. Groeneveld, Geert Jan |
author_facet | Bakker, Charlotte van der Aart, Jasper Hart, Ellen P. Klaassen, Erica S. Bergmann, Kirsten R. van Esdonk, Michiel J. Kay, Denis G. Groeneveld, Geert Jan |
author_sort | Bakker, Charlotte |
collection | PubMed |
description | INTRODUCTION: Gln‐1062 (MEMOGAIN) is an intranasally administered lipophilic prodrug of galantamine. Based on high brain‐to‐blood concentrations observed in pre‐clinical studies, Gln‐1062 is expected to have superior cognitive efficacy compared to oral galantamine. METHODS: Forty‐eight healthy elderly subjects were randomized 12:4 to Gln‐1062 (5.5, 11, or 22 mg, b.i.d., for 7 days) or placebo. Safety, tolerability, pharmacokinetics, and pharmacodynamics were assessed repeatedly. Pharmacokinetics were compared with 16 mg oral galantamine. RESULTS: Gln‐1062 up to 22 mg, b.i.d., was well tolerated. Gln‐1062 plasma concentrations increased immediately following dosing (median T(max) of 0.5 hour [range 0.5‐1.0]). C(max) and AUC(0‐last) increased in a dose‐linear manner over all three dose levels. Gln‐1062 was rapidly cleaved into galantamine. Gln‐1062 significantly improved adaptive tracking (sustained attention) with 1.95% (95% confidence interval [CI] 0.630‐3.279, P = 0.0055) compared to placebo after correction for individual baseline performance. DISCUSSION: Gln‐1062 was considered to be safe and caused fewer gastrointestinal side effects than oral galantamine. Gln‐1062 behaved pharmacokinetically as expected and improved performance on cognitive tests. |
format | Online Article Text |
id | pubmed-7551138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75511382020-10-19 Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine Bakker, Charlotte van der Aart, Jasper Hart, Ellen P. Klaassen, Erica S. Bergmann, Kirsten R. van Esdonk, Michiel J. Kay, Denis G. Groeneveld, Geert Jan Alzheimers Dement (N Y) Research Articles INTRODUCTION: Gln‐1062 (MEMOGAIN) is an intranasally administered lipophilic prodrug of galantamine. Based on high brain‐to‐blood concentrations observed in pre‐clinical studies, Gln‐1062 is expected to have superior cognitive efficacy compared to oral galantamine. METHODS: Forty‐eight healthy elderly subjects were randomized 12:4 to Gln‐1062 (5.5, 11, or 22 mg, b.i.d., for 7 days) or placebo. Safety, tolerability, pharmacokinetics, and pharmacodynamics were assessed repeatedly. Pharmacokinetics were compared with 16 mg oral galantamine. RESULTS: Gln‐1062 up to 22 mg, b.i.d., was well tolerated. Gln‐1062 plasma concentrations increased immediately following dosing (median T(max) of 0.5 hour [range 0.5‐1.0]). C(max) and AUC(0‐last) increased in a dose‐linear manner over all three dose levels. Gln‐1062 was rapidly cleaved into galantamine. Gln‐1062 significantly improved adaptive tracking (sustained attention) with 1.95% (95% confidence interval [CI] 0.630‐3.279, P = 0.0055) compared to placebo after correction for individual baseline performance. DISCUSSION: Gln‐1062 was considered to be safe and caused fewer gastrointestinal side effects than oral galantamine. Gln‐1062 behaved pharmacokinetically as expected and improved performance on cognitive tests. John Wiley and Sons Inc. 2020-10-13 /pmc/articles/PMC7551138/ /pubmed/33083515 http://dx.doi.org/10.1002/trc2.12093 Text en © 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Bakker, Charlotte van der Aart, Jasper Hart, Ellen P. Klaassen, Erica S. Bergmann, Kirsten R. van Esdonk, Michiel J. Kay, Denis G. Groeneveld, Geert Jan Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine |
title | Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine |
title_full | Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine |
title_fullStr | Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine |
title_full_unstemmed | Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine |
title_short | Safety, pharmacokinetics, and pharmacodynamics of Gln‐1062, a prodrug of galantamine |
title_sort | safety, pharmacokinetics, and pharmacodynamics of gln‐1062, a prodrug of galantamine |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551138/ https://www.ncbi.nlm.nih.gov/pubmed/33083515 http://dx.doi.org/10.1002/trc2.12093 |
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