Lack of a Pharmacokinetic Interaction Between Saxagliptin and Dapagliflozin in Healthy Subjects: A Randomized Crossover Study.
PURPOSE
This single-dose, open-label, randomized, 3-period, 3-treatment crossover drug-drug interaction study was conducted to evaluate differences in the pharmacokinetic properties of saxagliptin and dapagliflozin when coadministered.


METHODS
Healthy subjects (N = 42) were randomized to receive saxagliptin 5 mg alone, dapagliflozin 10 mg alone, or saxagliptin 5 mg plus dapagliflozin 10 mg coadministered; there was a washout period of ≥6 days between treatments. Serial blood samples for determining saxagliptin, 5-hydroxy saxagliptin (5-OH saxagliptin; major active metabolite) and dapagliflozin plasma concentrations and pharmacokinetic parameters were collected before and up to 60 hours after the dose. No interaction was to be concluded if the 90% CIs for the geometric mean ratios of the combination compared with each drug given alone for Cmax and AUCinf were within 0.80 to 1.25.


FINDINGS
The results indicated that dapagliflozin had no effect on the pharmacokinetic properties of saxagliptin, 5-OH saxagliptin, or saxagliptin total active moiety and vice versa. The 90% CIs for Cmax and AUCinf for all comparisons were contained entirely within the 0.80 to 1.25 equivalence intervals. Other pharmacokinetic parameters (apparent oral clearance or half-life) of saxagliptin or dapagliflozin were similar when each medicine was administered alone or when coadministered. No safety profile or tolerability findings of concern were observed during the study. All adverse events were mild, and no serious adverse events were reported.


IMPLICATIONS
These data indicate that coadministration of saxagliptin and dapagliflozin exhibits no pharmacokinetic interaction and is well tolerated. ClinicalTrials.gov identifier: NCT01662999.
['Vakkalagadda|Blisse|B|', 'Lubin|Susan|S|', 'Reynolds|Laurie|L|', 'Liang|Dan|D|', 'Marion|Alan S|AS|', 'LaCreta|Frank|F|', 'Boulton|David W|DW|']
D000218:Adamantane D000284:Administration, Oral D000328:Adult D001559:Benzhydryl Compounds D018592:Cross-Over Studies D004151:Dipeptides D004347:Drug Interactions D005260:Female D005960:Glucosides D006207:Half-Life D006801:Humans D008297:Male D055815:Young Adult
saxagliptin dapagliflozin dipeptidyl peptidase-4 (DPP-4) inhibitor drug interaction sodium-glucose cotransporter 2 (SGLT-2) inhibitor