Dapagliflozin pharmacokinetics is similar between patients with heart failure with reduced ejection fraction and patients with type 2 diabetes mellitus

Dapagliflozin was recently approved for use in adults with chronic heart failure with reduced ejection fraction (HFrEF) with/without type 2 diabetes mellitus (T2DM). The objectives of this analysis were to characterize dapagliflozin pharmacokinetics in patients with HFrEF and to compare dapagliflozi...

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Bibliographic Details
Published in:British journal of clinical pharmacology 2024-02, Vol.90 (2), p.606-612
Main Authors: Melin, Johanna, Parkinson, Joanna, Hamrén, Bengt, Penland, Robert C., Boulton, David W., Tang, Weifeng
Format: Article
Language:English
Subjects:
Adult
Benzhydryl Compounds - adverse effects
dapagliflozin
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - drug therapy
Glucosides - adverse effects
Heart Failure - chemically induced
Heart Failure - drug therapy
heart failure with reduced ejection fraction
Humans
population pharmacokinetics
SGLT2 inhibitor
Stroke Volume
type 2 diabetes mellitus
Ventricular Dysfunction, Left - chemically induced
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Summary:Dapagliflozin was recently approved for use in adults with chronic heart failure with reduced ejection fraction (HFrEF) with/without type 2 diabetes mellitus (T2DM). The objectives of this analysis were to characterize dapagliflozin pharmacokinetics in patients with HFrEF and to compare dapagliflozin systemic exposure between adults with HFrEF with/without T2DM and adults with T2DM. A nonlinear mixed‐effects modelling approach was applied; the population‐pharmacokinetic model was developed using 9735 dapagliflozin plasma concentrations from 2744 patients. The final two‐compartmental model adequately described the observed dapagliflozin concentrations, with a similar estimated apparent clearance compared with a previous estimate in patients with T2DM without HF and in healthy subjects (23.0 [95% CI: 22.6–23.9] L/h vs. 22.9 [95% CI: 22.1–23.7] L/h). The model‐predicted median area under the dapagliflozin concentration–time profile was ≤1.2‐fold higher in patients with HFrEF vs. those with T2DM without HFrEF, which is not considered clinically relevant. Dapagliflozin exposure was similar between patients with HFrEF with/without T2DM and T2DM patients without HFrEF.
ISSN:0306-5251
1365-2125
DOI:10.1111/bcp.15939