(1) Design and implement in vitro a novel model for evaluating the presence of highly permeable drugs in the upper gastrointestinal lumen when antro-duodenal drug transfer occurs after a high-calorie, high-fat meal by also considering throughput efficiency; (2) Assess the usefulness of the model in the evaluation of danazol and of itraconazole presence in the upper gastrointestinal lumen during the antro-duodenal drug transfer.

The design was based on published estimates for the parameters controlling the antro-duodenal transfer of highly permeable drugs after a high-calorie, high-fat meal. The performance of a four-compartment in vitro model was tested by using paracetamol solutions and verification was based on reproducibility, similarity with theoretically expected values, and (when using biorelevant media) in vivo relevance of data. The model was evaluated for its usefulness in reproducing published total amounts per volume and concentrations in the upper gastrointestinal lumen for danazol and itraconazole administered as 100 mg aqueous suspension and as 200 mg Sporanox® pellets, respectively, to the antrum of healthy adults after a high-calorie, high-fat meal and a glass of water. The model was established at a second laboratory to evaluate inter-laboratory data variability.

Based on data collected from two laboratories, maximum % RSD and maximum % bias from theoretically expected paracetamol total amounts per volume of antral and of duodenal contents were 18 and 9.4, respectively. Paracetamol data collected by using biorelevant media were in line with published luminal data in adults. Danazol and itraconazole total amounts per volume in the antral and in the duodenal compartment during the transfer process were in line with published data in adults. Danazol concentrations in the water content of antral compartment and in the micellar phase aqueous phase of duodenal compartment were in line with the lowest and the highest individual published data in adults, respectively. Itraconazole concentrations in the colloidal phase of aqueous content of duodenal compartment were higher than published data in adults. Itraconazole concentrations in the micellar phase of aqueous content of duodenal compartment slightly overestimated published data in the micellar phase of aqueous duodenal content in healthy adults.

For the first time an in vitro model for simulating the drug presence in the upper small intestine when antro-duodenal drug transfer occurs after a high-calorie, high-fat meal was evaluated against luminal data in adults. The model could be useful in parameterizing physiologically based biopharmaceutics (in silico) models.