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

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.

Two phase I studies, each comprising 12 healthy males, were performed. Gastrointestinal transit of (153)Sm-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.

(153)Sm-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 C(max) 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 t(max) increased by 12-29%. There was no drug accumulation after 1 week of once daily oral administration of budesomide.

MMX-budesonide tablets appear suitable for targeted colonic drug delivery. Transit parameters and low systemic bioavailability warrant further studies with the new formulation.