To investigate whether and to what extent the P-glycoprotein inhibitor (P-gp) verapamil affects the pharmacokinetic parameters of dabigatran with verapamil given at different dosages, in different formulations (immediate release (IR) and extended release (ER)), and in different intervals in relation to the dabigatran dose.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
AUC0-infinity (area under the concentration-time curve of total dabigatran over the time interval from 0 extrapolated to infinity)
Time frame: up to 107 hours
Cmax (maximum measured concentration of total dabigatran)
Time frame: up to 107 hours
AUC0-infinity (area under the concentration-time curve of free dabigatran over the time interval from 0 extrapolated to infinity)
Time frame: up to 107 hours
Cmax (maximum measured concentration of free dabigatran)
Time frame: up to 107 hours
AUC0-infinity (area under the concentration-time curve of verapamil over the time interval from 0 extrapolated to infinity)
Time frame: up to 107 hours
Cmax (maximum measured concentration of verapamil)
Time frame: up to 107 hours
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)
Time frame: up to 107 hours
AUC0-24 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 h after the administration)
Time frame: up to 107 hours
tmax (time from dosing to the maximum concentration of the analyte in plasma)
Time frame: up to 107 hours
λz (terminal rate constant in plasma)
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Time frame: up to 107 hours
t1/2 (terminal half-life of the analyte in plasma)
Time frame: up to 107 hours
MRTpo (mean residence time of the analyte in the body after oral administration)
Time frame: up to 107 hours
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
Time frame: up to 107 hours
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Time frame: up to 107 hours
AUCτ,ss (area under the concentration-time curve of verapamil within the uniform dosing interval τ)
Time frame: up to 107 hours
AUC0-tz,ss (area under the concentration-time curve of verapamil from the time point 0 after the last dose at steady state to the last quantifiable analyte plasma concentration within the uniform dosing interval τ)
Time frame: up to 107 hours
Cmax,ss (maximum concentration of verapamil at steady state)
Time frame: up to 107 hours
tz,ss (time of last measureable concentration of verapamil within the dosing interval τ at steady state)
Time frame: up to 107 hours
tmax,ss (time from last dosing to the maximum concentration of verapamil at steady state on day 4)
Time frame: up to 107 hours
CL/F,ss (apparent clearance of verapamil at steady state after extravascular multiple dose administration)
Time frame: up to 107 hours
Cmin,ss (minimum measured concentration of verapamil at steady state over a uniform dosing interval τ)
Time frame: up to 107 hours
tmin,ss (time from last dosing to the minimum concentration of verapamil at steady state over a uniform dosing interval τ)
Time frame: up to 107 hours
Cpre,ss (predose concentration of verapamil at steady state immediately before administration of the next dose)
Time frame: up to 107 hours
Cavg (Average concentration of verapamil at steady state)
Time frame: up to 107 hours
MRTpo,ss (mean residence time of verapamil in the body at steady state after oral administration)
Time frame: up to 107 hours
Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following an extravascular administration)
Time frame: up to 107 hours
Ae0-24 (amount of dabigatran that is eliminated in urine from the time interval 0-24h)
Time frame: up to 107 hours
fe0-24 (fraction of administered drug excreted unchanged in urine from time point 0- 24h)
Time frame: up to 107 hours
CLR0-24 (renal clearance of dabigatran from the time point 0 until the time point 24h )
Time frame: up to 107 hours
AUEC0-24 (area under the effect curve)
for ecarin clotting time and thrombin time
Time frame: up to 107 hours
ERmax (maximum effect ratio)
for ecarin clotting time and thrombin time
Time frame: up to 107 hours
Occurence of Adverse Events
Time frame: within 5 days after last drug administration
Assessment of Tolerability by investigator
Time frame: within 5 days after last drug administration