Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide formulation

Aims The aims of the study were to: (1) evaluate the gastrointestinal transit, release and absorption of budesonide from tablets with a new multimatrix formulation (MMX®) designed to release the drug throughout the whole colon, and (2) assess the influence of food on budesonide bioavailability. Methods Two phase I studies, each comprising 12 healthy males, were performed. Gastrointestinal transit of 153Sm‐labelled tablets containing 9 mg budesonide was evaluated by means of pharmaco‐scintigraphy. The effect of food was tested by comparing plasma pharmacokinetics after intake of a high fat and high calorie breakfast with fasting controls. Results 153Sm‐labelled tablets reached the ascending colon after a mean ± SD 9.8 ± 6.9 h. Initial tablet disintegration was observed in the ileum in 42% and the ascending and transverse colon in 33% of subjects. Ninety‐six per cent of the dose was absorbed into the systemic circulation during passage through the whole colon including the sigmoid. Food significantly decreased Cmax values from 1429 ± 1014 to 1040 ± 601 pg mL−1 (P = 0.028) and AUC values from 14 814 ± 11 254 to 13 486 ± 9369 pg h−1 mL−1 (P = 0.008). Mean residence time and tmax increased by 12–29%. There was no drug accumulation after 1 week of once daily oral administration of budesomide. Conclusions MMX®‐budesonide tablets appear suitable for targeted colonic drug delivery. Transit parameters and low systemic bioavailability warrant further studies with the new formulation.