Bioequivalence of fixed-dose combinations of dapagliflozin and metformin with single-component tablets in healthy subjects and the effect of food on bioavailability.

The pharmacokinetics (PK) of dapagliflozin and metformin administered as fixed-dose combination (FDC) tablets (2.5 mg dapagliflozin/850 mg metformin or 5 mg dapagliflozin/1000 mg metformin) or as separate tablets in healthy subjects were evaluated in 2 separate studies. Study 1 evaluated PK by measuring mean ratios of area under the plasma concentration-time curve (time zero to infinity [AUCinf ]), AUC from zero to time of last measurable concentration (AUC0-t ), and maximum observed plasma concentration (Cmax ) for single-component or FDC tablets following a non-high-fat meal.

Dapagliflozin twice daily or once daily: effect on pharmacokinetics and urinary glucose excretion in healthy subjects.

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.

Effect of a high-fat meal on the pharmacokinetics of dapagliflozin, a selective SGLT2 inhibitor, in healthy subjects.

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)].

Lack of correlation between exercise and sibenadet-induced changes in heart rate corrected measurement of the QT interval.

Aims: We sought to investigate subject specific QT interval correction factors (SSCF) determined at rest and after exercise and to determine the validity of these factors after the administration of a probe drug known to increase heart rate without directly affecting cardiac repolarization.

Methods: Thirty-two healthy volunteers underwent graded exercise, multiple recordings of electrocardiogram during rest over a day and a treatment phase administering inhaled placebo or sibenadet (a beta(2)-adrenoceptor/dopamine D(2)-receptor agonist) at 250, 500 or one of 750 or 1000 microg. SSCF were determined from linear regression of plots of log RR interval vs.

Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics.

Aims: To explore the potential for drug interactions on quetiapine pharmacokinetics using in vitro and in vivo assessments.

Methods: The CYP enzymes responsible for quetiapine metabolite formation were assessed using recombinant expressed CYPs and CYP-selective inhibitors. P-glycoprotein (Pgp) transport was tested in MDCK cells expressing the human MDR1 gene.