Utilizing Tiny-TIM to Assess the Effect of Acid-Reducing Agents on the Absorption of Orally Administered Drugs
| Autor: | Karthik Nagapudi, Jia Liu, Po-Chang Chiang, Michael J. Dolton |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Drug
media_common.quotation_subject Administration Oral Pharmaceutical Science 02 engineering and technology Absorption (skin) Pharmacology Models Biological 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Humans Medicine Drug Interactions heterocyclic compounds Pharmaceutical industry media_common business.industry food and beverages biochemical phenomena metabolism and nutrition 021001 nanoscience & nanotechnology carbohydrates (lipids) Intestinal Absorption Pharmaceutical Preparations Solubility Reducing Agents 0210 nano-technology business |
| Zdroj: | Journal of Pharmaceutical Sciences. 110:3020-3026 |
| ISSN: | 0022-3549 |
| DOI: | 10.1016/j.xphs.2021.04.017 |
| Popis: | Acid-reducing agents (ARAs) are the most commonly used medicines to treat patients with gastric acid-related disorders. ARA administration results in an elevation of intragastric pH and eases symptoms such as acid reflux. However, this effect could also lead to a reduction in the absorption of some co-administered oral medications (i.e. weakly basic drugs) by decreasing their gastric solubility. This in turn can result in a significant reduction of the efficacy of the co-administered oral medications. In order to address this problem, substantial efforts in translational modeling and the development of predictive in-vitro assays to better forecast the effect of ARA on oral absorption are conducted in the pharmaceutical industry. Despite these efforts, it remains challenging to predict the impact of ARAs on co-administered drugs. In this study, we evaluated the utility of Triskelion's Gastro-Intestinal Model (Tiny-TIM) in predicting ARA effect on twelve model drugs whose in-vivo data are available. The Tiny-TIM prediction of the ARA effect matched the observed effect of ARA co-administration in humans for the 12 model compounds. In summary, Tiny-TIM is a very reliable and promising GI model to successfully predict the nature of DDI when ARAs are co-administered with the drug of interest. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|