{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T21:13:05Z","timestamp":1774732385553,"version":"3.50.1"},"reference-count":13,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>N\u2010acetyl\u2010D\u2010mannosamine monohydrate (ManNAc) is a naturally occurring monosaccharide that has attracted considerable attention for its potential in treating GNE myopathy, a rare autosomal recessive muscle disorder. Despite its promise as an oral treatment, the absolute bioavailability of oral ManNAc has not been determined and there has been no evaluation of the ManNAc pharmacokinetics following intravenous administration in humans. The aim of this study was to investigate the pharmacokinetics of intravenous ManNAc and to characterize its absolute bioavailability following a single oral dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this single\u2010centre, open\u2010label, crossover study, six healthy adult males were administered ManNAc as a single oral dose (1000\u2009mg) and intravenous dose (100\u2009mg). Blood samples were collected over a 48\u2009h period after dose administration for the quantification of plasma ManNAc concentrations. Non\u2010compartmental pharmacokinetic analysis was performed using baseline\u2010corrected plasma concentration\u2013time data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After intravenous dosing, the mean plasma clearance of ManNAc was 10.1\u2009\u00b1\u20091.94\u2009L\/h, volume of distribution was 24.1\u2009\u00b1\u20094.98\u2009L and elimination half\u2010life was 1.67\u2009\u00b1\u20090.251\u2009h. The mean absolute bioavailability of oral ManNAc at a dose of 1000\u2009mg was 4.01\u2009\u00b1\u20091.82%. Deconvolution analysis revealed a zero\u2010order absorption rate of about 10\u00a0mg per hour in the initial 3\u00a0h after dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The low oral bioavailability of ManNAc is likely due to poor absorption (rather than first\u2010pass hepatic extraction) due to its high polarity. In addition, zero\u2010order absorption explains why the systemic exposure to ManNAc does not increase proportionally with dose.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70292","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T04:35:30Z","timestamp":1758256530000},"page":"488-494","source":"Crossref","is-referenced-by-count":1,"title":["Absolute bioavailability and intravenous pharmacokinetics of N\u2010acetyl\u2010D\u2010mannosamine in humans"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7827-6256","authenticated-orcid":false,"given":"Tahlia R.","family":"Meola","sequence":"first","affiliation":[{"name":"UniSA Clinical &amp; Health Sciences University of South Australia  Adelaide SA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Ludbrook","sequence":"additional","affiliation":[{"name":"PARC Clinical Research  Adelaide SA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianfranco","family":"Fornasini","sequence":"additional","affiliation":[{"name":"Leadiant Biosciences, Inc.  Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Pavlova","sequence":"additional","affiliation":[{"name":"Leadiant Biosciences, Inc.  Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumit","family":"Jain","sequence":"additional","affiliation":[{"name":"Leadiant Biosciences, Inc.  Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan M.","family":"Evans","sequence":"additional","affiliation":[{"name":"UniSA Clinical &amp; Health Sciences University of South Australia  Adelaide SA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-7287","authenticated-orcid":false,"given":"Stephanie E.","family":"Reuter","sequence":"additional","affiliation":[{"name":"UniSA Clinical &amp; Health Sciences University of South Australia  Adelaide SA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22583"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2014.03.004"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102013\u2010307051"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2008.06.002"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.04.010"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1433"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010021\u201001259\u2010x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2015.07.018"},{"key":"e_1_2_10_10_1","volume-title":"Guidance for industry; M10 bioanalytical method validation and study sample analysis","author":"Food and Drug Administration","year":"2022"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15537"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40268\u2010021\u201000343\u20106"},{"key":"e_1_2_10_13_1","volume-title":"Physiology, water balance","author":"Tobias A","year":"2023"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12551\u2010015\u20100186\u20102"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70292","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bcp.70292","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70292","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:54:40Z","timestamp":1770908080000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":13,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/bcp.70292"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70292","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]}}}