title: Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide formulation.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Vienna, Austria. martin.brunner@meduniwien.ac.at
authors.forename: M
authors.initials: M
authors.lastname: Brunner
authors.forename: S
authors.initials: S
authors.lastname: Ziegler
authors.forename: A F D
authors.initials: AF
authors.lastname: Di Stefano
authors.forename: P
authors.initials: P
authors.lastname: Dehghanyar
authors.forename: K
authors.initials: K
authors.lastname: Kletter
authors.forename: M
authors.initials: M
authors.lastname: Tschurlovits
authors.forename: R
authors.initials: R
authors.lastname: Villa
authors.forename: R
authors.initials: R
authors.lastname: Bozzella
authors.forename: G
authors.initials: G
authors.lastname: Celasco
authors.forename: L
authors.initials: L
authors.lastname: Moro
authors.forename: A
authors.initials: A
authors.lastname: Rusca
authors.forename: R
authors.initials: R
authors.lastname: Dudczak
authors.forename: M
authors.initials: M
authors.lastname: Müller
mesh_terms: 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
chemical_list: D000893:Anti-Inflammatory Agents; D004041:Dietary Fats; D019819:Budesonide