Safety, pharmacokinetics, and pharmacodynamics of Gln-1062, a prodrug of galantamine
| Autor: | Denis G. Kay, Michiel J van Esdonk, Charlotte Bakker, Ellen P. Hart, Kirsten R. Bergmann, Geert Jan Groeneveld, Jasper van der Aart, Erica S. Klaassen |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
safety Cmax Pharmacology Placebo 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Galantamine medicine pharmacodynamics cholinesterase inhibitor Dosing RC346-429 Research Articles business.industry RC952-954.6 Prodrug Alzheimer's disease Psychiatry and Mental health side effects 030104 developmental biology Tolerability Geriatrics Pharmacodynamics randomized controlled trial Neurology. Diseases of the nervous system Neurology (clinical) pharmacology business pharmacokinetics 030217 neurology & neurosurgery galantamine Research Article medicine.drug dementia |
| Zdroj: | Alzheimer's and Dementia: Translational Research and Clinical Interventions, 6(1). WILEY Alzheimer's & Dementia : Translational Research & Clinical Interventions Alzheimer’s & Dementia: Translational Research & Clinical Interventions, Vol 6, Iss 1, Pp n/a-n/a (2020) |
| Popis: | 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 Tmax of 0.5 hour [range 0.5‐1.0]). Cmax and AUC0‐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. |
| Databáze: | OpenAIRE |
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