English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Aims  To quantitate the consistency of an individual's plasma exposure to dapagliflozin upon re‐exposure, and to investigate whether the individual's systemic exposure to dapagliflozin explains inter‐individual variation in response to dapagliflozin with regard to multiple renal risk markers.    Methods  Data were used from a crossover randomized clinical trial that assessed the albuminuria‐lowering effect of dapagliflozin in 33 people with type 2 diabetes and elevated albuminuria. Fifteen participants were exposed twice to dapagliflozin. Trough plasma concentrations of dapagliflozin were measured for each participant at steady state. Dapagliflozin plasma concentrations were measured by liquid chromatography tandem mass spectrometry, and pharmacokinetic characteristics were simulated based on a population pharmacokinetic model. Linear mixed‐effects models were used to quantify the exposure–response relationships.    Results  The median plasma concentration after first and second exposure to dapagliflozin was 5.3 ng/mL vs 4.6 ng/mL, respectively ( P  = 0.78). Lin's concordance correlation coefficient between occasions was 0.73 ( P  < 0.0021). Every 100 ng.h/mL increment in area under the dapagliflozin plasma concentration curve was associated with a decrease in log‐transformed urinary albumin:creatinine ratio (β = −5.9,  P  < 0.01), body weight (β = −0.3,  P  < 0.01) and estimated glomerular filtration rate (β = −0.7,  P  = 0.01) and an increase in urinary glucose excretion (β = 17.0,  P  < 0.001).    Conclusion  An individual's exposure to dapagliflozin is consistent upon re‐exposure and correlates with pharmacodynamic response in renal risk markers.

Exposure–response relationships for the sodium‐glucose co‐transporter‐2 inhibitor dapagliflozin with regard to renal risk markers