Lack of pharmacokinetic interactions between dapagliflozin and simvastatin,
valsartan, warfarin, or digoxin.
Author(s): Kasichayanula S, Chang M, Liu X, Shyu WC, Griffen SC, LaCreta FP, Boulton DW.
Affiliation(s): Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb Company,
Princeton, NJ 08543-4000, USA. sreeneeranj.kasichayanula@bms.com
Publication date & source: 2012, Adv Ther. , 29(2):163-77
INTRODUCTION: Coronary heart disease, stroke, and peripheral vascular disease are
the most common causes of mortality in patients with type 2 diabetes mellitus
(T2DM). The aim of these studies was to assess the potential for pharmacokinetic
interaction between dapagliflozin, a sodium glucose co-transporter-2 inhibitor
being developed for the treatment of T2DM, and four medications commonly
prescribed in patients with T2DM and cardiovascular disease: simvastatin,
valsartan, warfarin, and digoxin.
METHODS: Potential pharmacokinetic interactions between 20 mg dapagliflozin, 40
mg simvastatin, or 320 mg valsartan were assessed in an open-label, randomized,
five-period, five-treatment, unbalanced crossover study in 24 healthy subjects.
In a second study, the effects of steady-state dapagliflozin on the
pharmacokinetics of 25 mg warfarin or 0.25 mg digoxin were assessed in an
open-label, randomized, two-period, two-treatment crossover study in 30 healthy
subjects divided into two cohorts. The potential pharmacodynamic interaction
between dapagliflozin and warfarin was also evaluated.
RESULTS: All treatments were well tolerated. Neither simvastatin nor valsartan
had any clinically meaningful effect on the pharmacokinetics of dapagliflozin.
Dapagliflozin increased the area under the curve for simvastatin, simvastatin
acid, and valsartan by approximately 19%, 30%, and 6%, respectively, and
decreased the maximum observed plasma concentration of valsartan by approximately
6%. These effects were not considered clinically meaningful. In addition,
dapagliflozin had no effect on the pharmacokinetics of either digoxin or
warfarin. The pharmacodynamics of warfarin were also unaffected by dapagliflozin.
CONCLUSION: In these studies the co-administration of dapagliflozin and
simvastatin, valsartan, warfarin, or digoxin was well tolerated without
clinically meaningful drug-drug interaction.
|