Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide formulation.
OBJECTIVE
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.
Brunner
M
M
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Vienna, Austria. martin.brunner@meduniwien.ac.at
Ziegler
S
S
Di Stefano
A F D
AF
Dehghanyar
P
P
Kletter
K
K
Tschurlovits
M
M
Villa
R
R
Bozzella
R
R
Celasco
G
G
Moro
L
L
Rusca
A
A
Dudczak
R
R
Müller
M
M
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D019819:Budesonide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003106:Colon / Q000000981:diagnostic imaging / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D002149:Energy Intake / Q000502:physiology; D005502:Food; D005772:Gastrointestinal Transit / Q000502:physiology*; D006801:Humans; D007082:Ileum / Q000000981:diagnostic imaging / Q000378:metabolism; D007421:Intestine, Small / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D011877:Radionuclide Imaging
D000893:Anti-Inflammatory Agents; D004041:Dietary Fats; D019819:Budesonide