title: Effect of a high-fat meal on the pharmacokinetics of dapagliflozin, a selective SGLT2 inhibitor, in healthy subjects.
abstract: Dapagliflozin is a potent and selective inhibitor of sodium-glucose co-transporter type 2 that is being developed for the treatment of type 2 diabetes mellitus. This open-label, randomized, two-period, two-treatment (single doses of 10-mg dapagliflozin fasted or fed), crossover study was conducted to evaluate the effect of a high-fat meal on the pharmacokinetics of dapagliflozin in 14 healthy subjects. Compared to the fasted state, a high-fat meal decreased mean dapagliflozin maximum plasma concentrations (C(max) ) by 31%, increased the time to C(max) (T(max) ) by 1 h, but did not affect overall dapagliflozin systemic exposure [area under the plasma concentration-time curve (AUC)]. As the cumulative (daily) amount of glucose excreted in the urine induced by dapagliflozin is dependent upon dapagliflozin AUC, the effect of food on dapagliflozin C(max) is unlikely to have a clinically meaningful effect on dapagliflozin's efficacy. On the basis of these findings, dapagliflozin can be administered without regard to meals.
authors: R&D, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, USA. sreeneeranj.kasichayanula@bms.com
authors: S
authors: S
authors: Kasichayanula
authors: X
authors: X
authors: Liu
authors: W
authors: W
authors: Zhang
authors: M
authors: M
authors: Pfister
authors: S B
authors: SB
authors: Reele
authors: A-F
authors: AF
authors: Aubry
authors: F P
authors: FP
authors: LaCreta
authors: D W
authors: DW
authors: Boulton
mesh_terms: D000293:Adolescent; D000328:Adult; D001559:Benzhydryl Compounds; D001682:Biological Availability; D004032:Diet; D004041:Dietary Fats; D004305:Dose-Response Relationship, Drug; D005260:Female; D018565:Food-Drug Interactions; D005960:Glucosides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D004041:Dietary Fats; D005960:Glucosides; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C529054:dapagliflozin