Impact of Food on the Oral Absorption of N-Acetyl-D-Mannosamine in Healthy Men and Women
Date
2024
Authors
Evans, A.M.
Fornasini, G.
Meola, T.R.
Gahl, W.A.
Huizing, M.
Polasek, T.M.
Reuter, S.E.
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Journal article
Citation
Clinical Pharmacology in Drug Development, 2024; 13(8):876-883
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Abstract
N-Acetyl-D-mannosamine (ManNAc) is an endogenous monosaccharide and precursor of N-acetylneuraminic acid (Neu5Ac), a critical sialic acid. ManNAc is currently under clinical development to treat GNE myopathy, a rare muscle-wasting disease. In this randomized, open-label, 2-sequence, crossover study, 16 healthy women and men were administered a single oral dose of ManNAc under fasting and fed conditions. Blood samples were collected for 48 hours after dosing for quantification of plasma ManNAc and Neu5Ac concentrations. Noncompartmental pharmacokinetic and deconvolution analyses were performed using baseline-corrected plasma concentration data. Administration of ManNAc in the fed state resulted in a 1.6-fold increase in ManNAc exposure, compared to fasting conditions. A concurrent increase in Neu5Ac exposure was observed in the presence of food. Deconvolution analysis indicated that the findings were attributed to prolonged absorption rather than an enhanced rate of absorption. The impact of food on ManNAc pharmacokinetics was greater in women than men (fed/fasted area under the concentration-time curve from time 0 to infinity mean ratio: 198% compared to 121%). It is hypothesized that the presence of food slows gastric emptying, allowing a gradual release of ManNAc into the small intestine, translating into improved ManNAc absorption. The results suggest that taking ManNAc with food may enhance its therapeutic activity and/or reduce the daily dosage requirement.
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Data source: supplemental information, https://doi.org/10.1002/cpdd.1433
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Copyright 2024 The Authors. (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Access Condition Notes: This is an open access article under the terms of the Creative Commons Attribution-Non Commercial-No Derivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.