title: Increased bioavailability of celecoxib under fed versus fasted conditions is determined by postprandial bile secretion as demonstrated in a dynamic gastrointestinal model.
abstract: The objective of this study was to utilize physiologically relevant dynamic dissolution testing with the TNO intestinal model (TIM-1) in vitro gastrointestinal model to investigate the bioaccessibility of celecoxib. A single 200-mg dose of celecoxib was evaluated under average adult human physiological conditions simulated in the TIM-1 system. The in vitro data were compared with the clinically established pharmacokinetic data. When expressed as a percent of drug that progresses from the duodenum to the jejunum and ileum compartments (bioaccessible sites), the study demonstrated a 2-fold increase in the total bioaccessibility for celecoxib when co-administered with a high-fat meal as opposed to co-administration with a glass of water (fasted conditions). That increase in bioaccessibility was similar to a 1.2 to 1.6-fold increase in systemic exposure in adults and children following co-administration with a high-fat meal when compared to the exposure measured when celecoxib was co-administered with only water. Following that comparison, the flexibility of the TIM-1 system was used to more specifically investigate individual parameters of gastrointestinal conditions, such as the rate of bile secretion (emptying of the bile bladder) that accompanies high-fat meal consumption. We demonstrated that increased bile secretion after co-administration of a high-fat meal played a more important role in the increased celecoxib bioaccessibility than did the food matrix. This indicates that in humans without a bile bladder the exposure of celecoxib administered with food might be as low as under fasted state.
authors.affiliation: a Seventh Wave Laboratories , LLC , Chesterfield , MO , USA ;
authors.forename: Eric
authors.initials: E
authors.lastname: Lyng
authors.affiliation: b Department of Kinetics Research in Food and Pharma , TNO , Zeist , The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Havenaar
authors.affiliation: a Seventh Wave Laboratories , LLC , Chesterfield , MO , USA ;
authors.forename: Prathap
authors.initials: P
authors.lastname: Shastri
authors.affiliation: a Seventh Wave Laboratories , LLC , Chesterfield , MO , USA ;
authors.forename: Lucy
authors.initials: L
authors.lastname: Hetsco
authors.affiliation: a Seventh Wave Laboratories , LLC , Chesterfield , MO , USA ;
authors.forename: Andrew
authors.initials: A
authors.lastname: Vick
authors.affiliation: a Seventh Wave Laboratories , LLC , Chesterfield , MO , USA ;
authors.forename: John
authors.initials: J
authors.lastname: Sagartz
mesh_terms: D000328:Adult; D001646:Bile / Q000378:metabolism*; D001682:Biological Availability; D000068579:Celecoxib / Q000493:pharmacokinetics*; D059305:Diet, High-Fat / Q000379:methods; D005215:Fasting / Q000378:metabolism*; D005502:Food; D018565:Food-Drug Interactions / Q000502:physiology; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D012995:Solubility
chemical_list: D000068579:Celecoxib
keywords: Bioaccessibility; biorelavant; dissolution; gastrointestinal; in vitro testing