{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T08:33:42Z","timestamp":1776846822334,"version":"3.51.2"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,9,30]],"date-time":"2016-09-30T00:00:00Z","timestamp":1475193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of the study was to evaluate the bioavailability and clinical benefits of oral new formulation (HB<jats:sub>12<\/jats:sub>) of hydroxocobalamin (Hdrx) with <jats:italic>Hibiscus sabdariffa<\/jats:italic> (HS). First, in an observational study, a cohort of 30 vitamin B<jats:sub>12<\/jats:sub>\u2010deficient patients (vit B<jats:sub>12<\/jats:sub> &lt; 200 pg\/mL) with neurological symptoms received oral fixed dose of Hdrx containing 15 mg Hdrx daily for 10 days followed by 15 mg monthly. Clinical benefits were evaluated on haematological and biochemical parameters, and neurological improvement at days 10 and 90 compared to day 0. To understand the mechanism, intestinal mucosa from mice were mounted in vitro in Ussing chambers to measure Hdrx Fluxes. In the clinical study, serum vitamin B<jats:sub>12<\/jats:sub> level increased from 55.1 \u00b1 36.9 to 1330 \u00b1 335.5 pg\/mL at day 10 and 431.0 \u00b1 24.27 pg\/mL at day 90, without overt adverse effects. In mice ileum, (i) intestinal bioavailability of Hdrx increased in dose\u2010dependent manner with HB<jats:sub>12<\/jats:sub>. The apparent permeability of Hdrx was <jats:italic>P<\/jats:italic><jats:sub>app<\/jats:sub> = 34.9 \u00b1 4.6 \u00d7 10<jats:sup>\u22126<\/jats:sup> cm\/s in the presence of 3 mg\/mL (HB<jats:sub>12<\/jats:sub>B) compared to the control <jats:italic>P<\/jats:italic><jats:sub>app<\/jats:sub> = 6.2 \u00b1 0.7 \u00d7 10<jats:sup>\u22126<\/jats:sup> cm\/s. (ii) Total transepithelial electrical conductance (<jats:italic>G<\/jats:italic><jats:sub>t<\/jats:sub>) increased in dose\u2010dependent manner with HB<jats:sub>12<\/jats:sub>, <jats:italic>G<\/jats:italic><jats:sub>t<\/jats:sub> = 161.5 \u00b1 10.8 mS\/cm\u00b2 with HB<jats:sub>12<\/jats:sub>B (Hdrx 1 mg + HS 3 mg) compared to the control Hdrx, <jats:italic>G<\/jats:italic><jats:sub>t<\/jats:sub> = 28.7 \u00b1 4.0 mS\/cm\u00b2. In conclusion, the clinical study suggests that injections are not required when Hdrx is given orally. Intestinal bioavailability of Hdrx increased in vitro when it was used concomitantly with HS.<\/jats:p>","DOI":"10.1111\/fcp.12220","type":"journal-article","created":{"date-parts":[[2016,7,14]],"date-time":"2016-07-14T14:04:47Z","timestamp":1468505087000},"page":"568-576","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<i>Hibiscus sabdariffa<\/i> increases hydroxocobalamin oral bioavailability and clinical efficacy in vitamin B<sub>12<\/sub> deficiency with neurological symptoms"],"prefix":"10.1111","volume":"30","author":[{"given":"Zouhayr","family":"Souirti","sequence":"first","affiliation":[{"name":"Neurology Department Hassan II University Hospital Route de Sidi Harem 30000 Fez Morocco"},{"name":"Laboratory of Clinical Neuroscience Faculty of Medicine and Pharmacy of Fez Sidi Mohamed Ben Abdellah University Route de Sidi Harem 30000 Fez Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mouna","family":"Loukili","sequence":"additional","affiliation":[{"name":"Neurology Department Hassan II University Hospital Route de Sidi Harem 30000 Fez Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imar D.","family":"Soudy","sequence":"additional","affiliation":[{"name":"TransCell\u2010Lab Laboratory Faculty of Medicine Xavier Bichat University of Paris Diderot \u2013 Paris 7 75890 Paris Cedex 18 France"},{"name":"Biotechnop\u00f4le IRED Ndjam\u00e9na and Institut Universitaire des Sciences et Techniques d'Ab\u00e9ch\u00e9 B.P. 433 N'Djam\u00e9na Tchad"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaies","family":"Rtibi","sequence":"additional","affiliation":[{"name":"TransCell\u2010Lab Laboratory Faculty of Medicine Xavier Bichat University of Paris Diderot \u2013 Paris 7 75890 Paris Cedex 18 France"},{"name":"Physiology and Nutrition Laboratory Facult\u00e9 des Sciences de Tunis Tunis 2092 Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aslihan","family":"\u00d6zel","sequence":"additional","affiliation":[{"name":"TransCell\u2010Lab Laboratory Faculty of Medicine Xavier Bichat University of Paris Diderot \u2013 Paris 7 75890 Paris Cedex 18 France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Limas\u2010Nzouzi","sequence":"additional","affiliation":[{"name":"TransCell\u2010Lab Laboratory Faculty of Medicine Xavier Bichat University of Paris Diderot \u2013 Paris 7 75890 Paris Cedex 18 France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seloua","family":"El Ouezzani","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroendocrinology and Nutritional and Climatic Environment Faculty of Sciences Dhar El Mehraz B.P. 1796 F\u00e8s \u2010 Atlas \u2010 Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Eto","sequence":"additional","affiliation":[{"name":"TransCell\u2010Lab Laboratory Faculty of Medicine Xavier Bichat University of Paris Diderot \u2013 Paris 7 75890 Paris Cedex 18 France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,9,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i13.3542"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2014.01.057"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/424651"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-003-0323-2"},{"key":"e_1_2_6_6_1","first-page":"1077","article-title":"Old or new medicine? 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