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

2005; Wiley; Volume: 61; Issue: 1 Linguagem: Inglês

10.1111/j.1365-2125.2005.02517.x

1365-2125

Martin Brunner, S. Ziegler, Andrea F. D. Di Stefano, Pejman Dehghanyar, Kurt Kletter, M. Tschurlovits, Roberto Edoardo Villa, Roberta Bozzella, Giuseppe Celasco, L. Moro, Antonio Rusca, Robert Dudczak, M. Müller,

Inflammatory Bowel Disease

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