The effect of food and formulation on the population pharmacokinetics of cholesteryl ester transferase protein inhibitor DRL‐17822 in healthy male volunteers

We aimed to characterise the population pharmacokinetics of cholesteryl ester transferase protein inhibitor DRL‐17822 in healthy males and explore the effect of food and formulation on the oral absorption of DRL‐17822 in 4 phase I studies. DRL‐17822 was dosed orally (2–1000 mg) in 2 different drug formulations (nanocrystal formulation and amorphous solid dispersion formulation) after either an overnight fast, or a low‐fat, continental or high‐fat breakfast. A 2‐compartment model with 6 transit absorption compartments best characterised the data. Additionally, a strong interaction of food and formulation on bioavailability was observed and parsimoniously characterised in the model by binning combinations of food state and formulation with similar bio‐availabilities. The final model adequately characterised the pharmacokinetic data of DRL‐17822 in healthy males including the complex interaction of food and drug formulation. The amorphous solid dispersion formulation has a lower food effect on bioavailability compared with the nanocrystal formulation.