دورية أكاديمية
Safety, Pharmacokinetics, and Biomarkers of an Amorphous Solid Dispersion of Genistein, a Radioprotectant, in Healthy Volunteers.
| العنوان: | Safety, Pharmacokinetics, and Biomarkers of an Amorphous Solid Dispersion of Genistein, a Radioprotectant, in Healthy Volunteers. |
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| المؤلفون: | Serebrenik AA; Humanetics Corporation, Minneapolis, Minnesota, USA., Verduyn CW; Medical Monitoring Consultancy, LLC, St. Paul, Minnesota, USA., Kaytor MD; Humanetics Corporation, Minneapolis, Minnesota, USA. |
| المصدر: | Clinical pharmacology in drug development [Clin Pharmacol Drug Dev] 2023 Feb; Vol. 12 (2), pp. 190-201. Date of Electronic Publication: 2022 Oct 27. |
| نوع المنشور: | Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
| 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: | Genistein*/adverse effects , Genistein*/blood , Genistein*/pharmacokinetics , Radiation-Protective Agents*/adverse effects , Radiation-Protective Agents*/pharmacokinetics, Humans ; Biological Availability ; Biomarkers/blood ; Drug Compounding/methods ; Healthy Volunteers |
| مستخلص: | A pharmaceutical formulation of genistein, produced as an amorphous solid dispersion by hot melt extrusion (genistein HME), has been developed that can be administered prophylactically to improve outcomes and survival following radiation exposure. Here, genistein HME was evaluated in a phase 1, open-label, single ascending dose (SAD) and multiple single dose (MSD) study enrolling 34 healthy volunteers. In the SAD study, participants were administered a single dose (500, 1000, 2000, or 3000 mg) and in the MSD study, participants were administered a single daily dose for six consecutive days (3000 mg/day). The overall adverse event profile and pharmacokinetics of genistein HME were determined. Additionally, biomarkers of genistein HME were evaluated by profiling whole blood for changes in gene expression by RNA sequencing. Genistein HME was found to be safe at doses up to 3000 mg. Most toxicities were mild to moderate gastrointestinal events, and no dose-limiting toxicities were reported. The maximum tolerated dose was not determined and the no observable adverse effect level was 500 mg. Genistein HME bioavailability greatly increased between the 2000 mg and 3000 mg doses. RNA sequencing analysis revealed that the majority of drug-related changes in gene expression occurred 8-12 hours after the sixth dose in the MSD study. Based on these results, the putative effective dose in humans is 3000 mg. (© 2022, The American College of Clinical Pharmacology.) |
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| فهرسة مساهمة: | Keywords: acute radiation syndrome; genistein; medical countermeasure; phase 1; radioprotectant |
| المشرفين على المادة: | 0 (Biomarkers) DH2M523P0H (Genistein) 0 (Radiation-Protective Agents) |
| تواريخ الأحداث: | Date Created: 20221027 Date Completed: 20230203 Latest Revision: 20230227 |
| رمز التحديث: | 20230228 |
| DOI: | 10.1002/cpdd.1188 |
| PMID: | 36301689 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2160-7648 |
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| DOI: | 10.1002/cpdd.1188 |