Dynamic population pharmacokinetic-pharmacodynamic modelling and simulation supports similar efficacy in glycosylated haemoglobin response with once or twice-daily dosing of canagliflozin.

ABSTRACT:

Aim

Canagliflozin is an SGLT2 inhibitor approved for the treatment of type-2 diabetes. A dynamic population pharmacokinetic-pharmacodynamic (PK/PD) model relating 24-h canagliflozin exposure profiles to effects on glycosylated haemoglobin was developed to compare the efficacy of once-daily and twice-daily dosing.

Methods

Data from two clinical studies, one with once-daily, and the other with twice-daily dosing of canagliflozin as add-on to metformin were used (n = 1347). An established population PK model was used to predict full 24-h profiles from measured trough concentrations and/or baseline covariates. The dynamic PK/PD model incorporated an E_max relationship between 24-h canagliflozin exposure and HbA1c-lowering with baseline HbA1c affecting the efficacy.

SUBMITTER: de Winter W 

PROVIDER: S-EPMC5401970 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature