Relationship Between Oral Semaglutide Tablet Erosion and Pharmacokinetics: A Pharmacoscintigraphic Study
| العنوان: | Relationship Between Oral Semaglutide Tablet Erosion and Pharmacokinetics: A Pharmacoscintigraphic Study |
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| المؤلفون: | Tine A. Bækdal, Flemming L. Søndergaard, Morten Donsmark, Marie-Louise Hartoft-Nielsen, Alyson Connor |
| المصدر: | Clinical Pharmacology in Drug Development |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, Glucagon-Like Peptides, Cmax, Administration, Oral, Pharmaceutical Science, Original Manuscript, sodium N‐(8‐[2‐hydroxybenzoyl] amino) caprylate, 030226 pharmacology & pharmacy, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, 0302 clinical medicine, Animal science, Pharmacokinetics, gastric absorption, medicine, scintigraphy, Humans, Hypoglycemic Agents, Pharmacology (medical), gastrointestinal transit, Radionuclide Imaging, Cross-Over Studies, Gastric emptying, glucagon‐like peptide‐1, business.industry, Gastrointestinal transit, Stomach, Semaglutide, Water, Articles, Fasting, Middle Aged, Crossover study, medicine.anatomical_structure, Median time, Area Under Curve, 030220 oncology & carcinogenesis, Caprylates, business, Tablets |
| الوصف: | Semaglutide, a glucagon‐like peptide‐1 (GLP‐1) analogue, has been coformulated in a tablet with the absorption enhancer, sodium N‐(8‐[2‐hydroxybenzoyl] amino) caprylate (SNAC). We investigated tablet erosion and the pharmacokinetics of oral semaglutide administered with 2 different water volumes and evaluated the relationships between these parameters. In a randomized, single‐center (Quotient Sciences, UK), open‐label, 2‐period crossover trial, 26 healthy men received single doses of 10 mg oral semaglutide with 50 or 240 mL water while fasting. Tablet erosion and gastrointestinal transit were assessed by gamma scintigraphy. Semaglutide and SNAC plasma concentrations were measured until 24 and 6 hours, respectively, after administration. Complete tablet erosion (CTE) occurred in the stomach irrespective of water volume administered with the tablet (primary end point). Mean time to CTE was 85 versus 57 minutes with 50 versus 240 mL water (ratio 50/240 mL, 1.51; 95% confidence interval, 0.96‐2.37; P = .072). Area under the semaglutide concentration‐time curve from 0 to 24 hours (AUC0‐24h,semaglutide) and maximum semaglutide concentration (Cmax,semaglutide) were ∼70% higher with 50 versus 240 mL water (P = .056 and P = .048, respectively). Median time to maximum semaglutide concentration (tmax,semaglutide) was 1.5 hours independent of water volume with dosing. Higher AUC0‐24h,semaglutide and Cmax,semaglutide and longer tmax,semaglutide were significantly correlated with longer time to CTE and later gastric emptying of tablet and water (all P < .05). The safety profile was as expected for the GLP‐1 receptor agonist drug class. In conclusion, the oral semaglutide tablet erodes in the stomach irrespective of water volume with dosing. Slower tablet erosion in the stomach results in higher semaglutide plasma exposure. |
| تدمد: | 2160-7648 2160-763X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::22737d91db0553ded98b50ed512b0c0e https://doi.org/10.1002/cpdd.938 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....22737d91db0553ded98b50ed512b0c0e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21607648 2160763X |
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