Investigation of drug partition kinetics to fat in simulated fed state gastric conditions based on drug properties
| Autor: | Nikoletta Fotaki, Jesse Kuiper, Fotios Baxevanis, Panagiota Zarmpi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
food.ingredient
Physicochemical properties Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Models Biological Gastric Content Partial least squares regression Fats 03 medical and health sciences Food-Drug Interactions 0302 clinical medicine food Pharmacokinetics In vivo Skimmed milk Humans Aqueous solution Chromatography Gastric Juice Drug partition Chemistry 021001 nanoscience & nanotechnology Food effect Partition coefficient Solubility Gastric Mucosa Lipophilicity Anhydrous Fed state 0210 nano-technology |
| Zdroj: | Baxevanis, F, Zarmpi, P, Kuiper, J & Fotaki, N 2020, ' Investigation of drug partition kinetics to fat in simulated fed state gastric conditions based on drug properties ', European Journal of Pharmaceutical Sciences, vol. 146, 105263 . https://doi.org/10.1016/j.ejps.2020.105263 |
| ISSN: | 1879-0720 |
| DOI: | 10.1016/j.ejps.2020.105263 |
| Popis: | The presence of fat in the gastric environment can affect the pharmacokinetic behaviour of drugs with mechanisms which have not been yet fully understood. The objective of the current study was to assess the drug partition to the lipid part of the fed gastric content under different emulsification conditions, using in vitro discriminating setups. The model drugs used in the study were selected on the basis of different physicochemical properties (lipophilicity, ionization, molecular weight and aqueous solubility) and different food effect observed in in vivo human studies. Fed State Simulated Gastric Fluid prepared with skimmed milk (FeSSGF sk) and anhydrous milk fat were used as surrogates for the aqueous and fat portions of the fed gastric environment respectively. An optimized biphasic model was developed so as to predict the differences in partition rate constants to fat, for model drugs of a wide range of the properties mentioned above. The experimental data and the use of statistical analysis revealed that molecular weight, molecular weight and log D pH 5 interaction and negative food effect act as negative factors to the rate constants of fat partition, while absence of food effect and logD pH 5 interaction with aqueous solubility affect the rate constants of partition to fat favourably. |
| Databáze: | OpenAIRE |
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