دورية أكاديمية
Impact of Food on the Oral Absorption of N-Acetyl-D-Mannosamine in Healthy Men and Women.
| العنوان: | Impact of Food on the Oral Absorption of N-Acetyl-D-Mannosamine in Healthy Men and Women. |
|---|---|
| المؤلفون: | Evans AM; UniSA Clinical & Health Sciences, University of South Australia, Adelaide, SA, Australia., Fornasini G; Leadiant Biosciences, Inc., Rockville, MD, USA., Meola TR; UniSA Clinical & Health Sciences, University of South Australia, Adelaide, SA, Australia., Gahl WA; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Huizing M; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Polasek TM; Certara, Princeton, NJ, USA.; Centre for Medicine Use and Safety, Monash University, Melbourne, Australia., Reuter SE; UniSA Clinical & Health Sciences, University of South Australia, Adelaide, SA, Australia. |
| المصدر: | Clinical pharmacology in drug development [Clin Pharmacol Drug Dev] 2024 Aug; Vol. 13 (8), pp. 876-883. Date of Electronic Publication: 2024 Jun 20. |
| نوع المنشور: | Journal Article; Randomized Controlled Trial |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley Country of Publication: United States NLM ID: 101572899 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2160-7648 (Electronic) Linking ISSN: 2160763X NLM ISO Abbreviation: Clin Pharmacol Drug Dev Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2013- : Hoboken, NJ : Wiley Original Publication: Thousand Oaks, Calif. : Sage Publications, c2012- |
| مواضيع طبية MeSH: | Cross-Over Studies* , Hexosamines*/administration & dosage , Hexosamines*/pharmacokinetics , Food-Drug Interactions* , N-Acetylneuraminic Acid*/administration & dosage , N-Acetylneuraminic Acid*/pharmacokinetics , N-Acetylneuraminic Acid*/blood, Humans ; Female ; Male ; Adult ; Administration, Oral ; Young Adult ; Middle Aged ; Fasting ; Healthy Volunteers ; Area Under Curve ; Intestinal Absorption |
| مستخلص: | 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. (© 2024 The Author(s). Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.) |
| References: | Celeste FV, Vilboux T, Ciccone C, et al. Mutation update for GNE gene variants associated with GNE myopathy. Hum Mutat. 2014;35(8):915‐926. Huizing M, Carrillo‐Carrasco N, Malicdan MCV, et al. GNE myopathy: new name and new mutation nomenclature. Neuromuscul Disord. 2014;24(5):387‐389. Amir SM, Barker SA, Butt WR, Crooke AC, Davies AG. Administration of N‐Acetyl‐D‐mannosamine to mammals. Nature. 1966;211(5052):976‐977. Gagiannis D, Orthmann A, Danßmann I, Schwarzkopf M, Weidemann W, Horstkorte R. Reduced sialylation status in UDP‐N‐acetylglucosamine‐2‐epimerase/N‐acetylmannosamine kinase (GNE)‐deficient mice. Glycoconj J. 2007;24(2‐3):125‐130. Galeano B, Klootwijk R, Manoli I, et al. Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N‐acetylmannosamine. J Clin Invest. 2007;117(6):1585‐1594. Malicdan MCV, Noguchi S, Hayashi YK, Nonaka I, Nishino I. Prophylactic treatment with sialic acid metabolites precludes the development of the myopathic phenotype in the DMRV‐hIBM mouse model. Nat Med. 2009;15(6):690. Niethamer TK, Yardeni T, Leoyklang P, et al. Oral monosaccharide therapies to reverse renal and muscle hyposialylation in a mouse model of GNE myopathy. Mol Genet Metab. 2012;107(4):748‐755. Thomas GH, Scocca J, Miller CS, Reynolds LW. Accumulation of N‐acetylneuraminic acid (sialic acid) in human fibroblasts cultured in the presence of N‐acetylmannosamine. Biochim Biophys Acta. 1985;846(1):37‐43. Xu X, Wang AQ, Latham LL, et al. Safety, pharmacokinetics and sialic acid production after oral administration of N‐acetylmannosamine (ManNAc) to subjects with GNE myopathy. Mol Genet Metab. 2017;122(1‐2):126‐134. Carrillo N, Malicdan MC, Leoyklang P, et al. Safety and efficacy of N‐acetylmannosamine (ManNAc) in patients with GNE myopathy: an open‐label phase 2 study. Genet Med. 2021;23:2067‐2075. Food and Drug Administration. Guidance for Industry; Food‐Effect Bioavailability and Fed Bioequivalence Studies. Center for Drug Evaluation and Research, U.S. Department of Health and Human Services; 2002. Shi Y, Xu X, Fang M, et al. Quantitative hydrophilic interaction chromatography–mass spectrometry analysis of N‐acetylneuraminic acid and N‐acetylmannosamine in human plasma. J Chromatogr B. 2015;1000:105‐111. Zou H, Banerjee P, Leung SSY, Yan X. Application of pharmacokinetic‐pharmacodynamic modeling in drug delivery: development and challenges. Review Front Pharmacol. 2020;11:997. Schwartz JB. The influence of sex on pharmacokinetics. Clin Pharmacokinet. 2003;42(2):107‐121. Van Wart S, Mager DE, Bednasz CJ, Huizing M, Carrillo N. Population pharmacokinetic model of N‐acetylmannosamine (ManNAc) and N‐acetylneuraminic acid (Neu5Ac) in subjects with GNE myopathy. Drugs R D. 2021;21(2):189‐202. Koziolek M, Alcaro S, Augustijns P, et al. The mechanisms of pharmacokinetic food‐drug interactions ‐ A perspective from the UNGAP group. Eur J Pharm Sci. 2019;134:31‐59. Welling PG. Effects of food on drug absorption. Pharmacol Ther. 1989;43(3):425‐441. Deng J, Zhu X, Chen Z, et al. A review of food‐drug interactions on oral drug absorption. Drugs. 2017;77(17):1833‐1855. Bennink R, Peeters M, Van den Maegdenbergh V, et al. Comparison of total and compartmental gastric emptying and antral motility between healthy men and women. Eur J Nucl Med. 1998;25(9):1293‐1299. Datz FL, Christian PE, Moore J. Gender‐related differences in gastric emptying. J Nucl Med. 1987;28(7):1204‐1207. |
| فهرسة مساهمة: | Keywords: N‐acetylneuraminic acid; N‐acetyl‐D‐mannosamine; food effect; oral absorption |
| المشرفين على المادة: | 0 (Hexosamines) X80PR7P73R (N-acetylmannosamine) GZP2782OP0 (N-Acetylneuraminic Acid) |
| تواريخ الأحداث: | Date Created: 20240620 Date Completed: 20240801 Latest Revision: 20240801 |
| رمز التحديث: | 20240801 |
| DOI: | 10.1002/cpdd.1433 |
| PMID: | 38899758 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2160-7648 |
|---|---|
| DOI: | 10.1002/cpdd.1433 |