Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide formulation.
Brunner, M. 1; Ziegler, S. 1; Di Stefano, A. F. D. 2; Dehghanyar, P. 1; Kletter, K. 3; Tschurlovits, M. 4; Villa, R. 5; Bozzella, R. 5; Celasco, G. 5; Moro, L. 5; Rusca, A. 2; Dudczak, R. 3; Muller, M. 1
[Miscellaneous Article]
British Journal of Clinical Pharmacology.
61(1):31-38, January 2006.
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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(R)) 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(R)-budesonide tablets appear suitable for targeted colonic drug delivery. Transit parameters and low systemic bioavailability warrant further studies with the new formulation.
Copyright (C) 2006 Blackwell Publishing Ltd.
