Pharmacokinetic and pharmacodynamic modelling for renal function dependent urinary glucose excretion effect of ipragliflozin, a selective sodium-glucose cotransporter 2 inhibitor, both in healthy subjects and patients with type 2 diabetes mellitus.

ABSTRACT:

Aims

To provide a model-based prediction of individual urinary glucose excretion (UGE) effect of ipragliflozin, we constructed a pharmacokinetic/pharmacodynamic (PK/PD) model and a population PK model using pooled data of clinical studies.

Methods

A PK/PD model for the change from baseline in UGE for 24 hours (ΔUGE_24h ) with area under the concentration-time curve from time of dosing to 24 h after administration (AUC_24h ) of ipragliflozin was described by a maximum effect model. A population PK model was also constructed using rich PK sampling data obtained from 2 clinical pharmacology studies and sparse data from 4 late-phase studies by the NONMEM $PRIOR subroutine. Finally, we simulated how the PK/PD of ipragliflozin changes in response to dose regime

SUBMITTER: Saito M 

PROVIDER: S-EPMC6624389 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature