title: Dapagliflozin twice daily or once daily: effect on pharmacokinetics and urinary glucose excretion in healthy subjects.
abstract: The primary objective of this single-centre, open-label crossover study (NCT01072578) was to assess the effect of dapagliflozin on the amount of glucose in the blood and urine in healthy volunteers when dapagliflozin was administered once a day (10 mg) versus twice a day (5 mg every 12 h) after 5 days of dosing. At steady state, the AUC(ss)₀₋₂₄ (area under the dapagliflozin curve (0-24 hours) at steady state), C(ss,av) (average concentration at steady state) between dapagliflozin 5 mg twice daily and 10 mg once daily were similar AUC(ss)₀₋₂₄ [5 mg bid, (458.0 (28.7)) and 10 mg qd, (470.0 (28.5))] and C(ss,av) [5 mg bid 18.8 (28.9)) and 10 mg qd, (19.6(28.5))], but minimum and maximum plasma levels of dapagliflozin differed significantly. Percent inhibition of renal glucose reabsorption (%IRGRA) and total urinary glucose excretion over 24 h were similar for both doses. The relationship between the mean dapagliflozin concentration and %IRGRA and the total urinary glucose excreted was well described by a maximum effect model. The results indicate that dapagliflozin may be used for either once daily or twice daily administration.
authors.affiliation: AstraZeneca, R&D, Wilmington, DE, USA.
authors.forename: W
authors.initials: W
authors.lastname: Tang
authors.forename: S
authors.initials: S
authors.lastname: Reele
authors.forename: J E
authors.initials: JE
authors.lastname: Hamer-Maansson
authors.forename: S
authors.initials: S
authors.lastname: Parikh
authors.forename: T W A
authors.initials: TW
authors.lastname: de Bruin
mesh_terms: D000293:Adolescent; D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001786:Blood Glucose / Q000032:analysis*; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005960:Glucosides / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006029:Glycosuria / Q000139:chemically induced*; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D065667:Renal Elimination / Q000187:drug effects; D065608:Renal Reabsorption / Q000187:drug effects; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C529054:dapagliflozin
keywords: dapagliflozin; once daily; pharmacodynamics; pharmacokinetics; twice daily