Pharmacokinetics and Pharmacodynamics of BI 10773 After Single and Multiple Oral Dose of 10 mg and 25 mg BI 10773 in Chinese Male and Female Type 2 Diabetic Patients

Apparent Clearance of Empagliflozin After Extravascular Administration (CL/F)

时间窗: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Apparent clearance of empagliflozin (empa) in plasma after extravascular administration, after the first dose on day 1.

Renal Clearance After Extravascular Administration (CL R,0-48)

时间窗: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Renal clearance of empagliflozin (empa) in plasma after extravascular administration, after the first dose on day 1.

Terminal Half-life (t1/2)

时间窗: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Terminal half-life of empagliflozin (empa) in plasma after the first dose on day 1

Mean Residence Time (MRTpo)

时间窗: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Mean residence time of empagliflozin (empa) in the body after the first dose on day 1.

Amount of Empagliflozin Eliminated in Urine in the Time Interval 0 Hours to 24 Hours (Ae 0-24)

时间窗: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

Amount of empagliflozin (empa) eliminated in urine in the time interval 0 hours to 24 hours, after the first dose on day 1.

Time From Last Dosing to Maximum Measured Concentration Over a Uniform Dosing Interval at Steady State (Tmax,ss)

时间窗: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Time from last dosing to maximum measured concentration of empagliflozin (empa) in plasma over a uniform dosing interval at steady state, after multiple dosing.

Terminal Rate Constant in Plasma at Steady State (λz,ss)

时间窗: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Terminal rate constant in plasma at steady state, after multiple dosing.

Apparent Volume of Distribution During the Terminal Phase λz (Vz/Fss)

时间窗: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Apparent volume of distribution during the terminal phase λz at steady state following oral administration after multiple dosing

Area Under the Curve 0 to Infinity (AUC0-∞) After Single Dosing

时间窗: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity, after the first dose on day 1

Terminal Rate Constant (λz)

时间窗: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Terminal Rate Constant in Plasma (λz), after the first dose on day 1

Apparent Volume of Distribution During the Terminal Phase λz (Vz/F)

时间窗: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Apparent volume of distribution during the terminal phase λz, after the first dose on day 1.

Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)

时间窗: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the time of the last quantifiable data point, after the first dose on day 1.

Area Under the Concentration-time Curve in Plasma at Steady State Over a Uniform Dosing Interval (AUCτ,ss)

时间窗: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Area under the concentration-time curve of empagliflozin (empa) in plasma at steady state over a uniform dosing interval, after multiple dosing

Mean Residence Time at Steady State (MRTpo,ss)

时间窗: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Mean residence time of empagliflozin (empa) in the body at steady state after multiple oral administrations

Amount of Analyte Eliminated in Urine at Steady State in Time Interval 0 Hours to 24 Hours (Ae 0-24,ss)

时间窗: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

Amount of empagliflozin (empa) eliminated in urine at steady state in the time interval 0 hours to 24 hours, after multiple dosing.

Maximum Measured Concentration (Cmax)

时间窗: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Maximum measured concentration of the analyte in plasma after the first dose on day 1.

Time to Maximum Measured Concentration (Tmax)

时间窗: 5 minutes (min) before drug administration and 10 min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h after drug administration

Time from dosing to the maximum measured concentration of the analyte in plasma, after the first dose on day 1.

Fraction of Empagliflozin Excreted Unchanged in Urine in the Time Interval 0 Hours to 24 Hours (fe 0-24).

时间窗: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

Fraction of empagliflozin (empa) excreted unchanged in urine in the time interval 0 hours to 24 hours, after the first dose on day 1.

Maximum Measured Concentration Over a Uniform Dosing Interval (Cmax,ss)

时间窗: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Maximum measured concentration of empagliflozin (empa) in plasma at steady state over a uniform dosing interval.

Terminal Half-life in Plasma at Steady State (t1/2,ss)

时间窗: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Terminal half-life of empagliflozin (empa) in plasma at steady state, after multiple dosing.

Apparent Clearance of Empagliflozin After Extravascular Administration (CL/Fss)

时间窗: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Apparent clearance of empagliflozin (empa) in the plasma at steady state following multiple oral dose administration.

Fraction of Empagliflozin Excreted Unchanged in Urine at Steady State in the Time Interval 0 Hours to 24 Hours (fe 0-24,ss)

时间窗: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

Fraction of empagliflozin (empa) excreted unchanged in urine at steady state in the time interval 0 hours to 24 hours, after multiple dosing.

Renal Clearance at Steady State (CL R,ss)

时间窗: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 36h 48h, 60h, 72h and 96h after drug administration on day 9

Renal clearance of empagliflozin (empa) in plasma after extravascular administration, after multiple dosing.

Accumulation Ratio Based on Cmax (R A,Cmax)

时间窗: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, and16h after drug administration between days 5 and 9

Accumulation ratio of empagliflozin (empa) based on Cmax, after multiple dosing

Predose Plasma Concentration Before Planned Dose x (Cpre,x)

时间窗: 5 minutes before drug administration

Predose plasma concentration of empagliflozin (empa) before planned dose by day. This endpoint in steady state is identical to Cmin,ss.

Accumulation Ratio Based on AUC (R A,AUC)

时间窗: 5 minutes (min) before drug administration and 10min, 20min, 30min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, and16h after drug administration on days 1 and 9

Accumulation ratio of empagliflozin (empa) based on AUC, after multiple dosing

Urinary Glucose Excretion (UGE) Change From Baseline

时间窗: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

Change from day -1 in urinary glucose excretion in a 24 hour collection period per time point.

Fasting Plasma Glucose (FPG) Change From Baseline

时间窗: Sampling intervals were 0-2 hours (h), 2-4h, 4-8h, 8-12h and 12-24h after drug administration

Fasting Plasma Glucose (FPG) change from baseline between day 1 and day 9.