Evolving data analysis of an Oral Lipid Tolerance Test toward the standard for the Oral Glucose Tolerance Test: Cross species modeling effects of AZD7687 on plasma triacylglycerol.

ABSTRACT: We have developed a novel mechanistic pharmacokinetic-pharmacodynamic (PK/PD) model to describe the time course of plasma triglyceride (TAG) after Oral Lipid Tolerance Test (OLTT) and the effects of AZD7687, an inhibitor of diacylglycerol acyltransferase 1 (DGAT1), in humans, rats, and mice. Pharmacokinetic and plasma TAG data were obtained both in animals and in two phase I OLTT studies. In the PK/PD model, the introduction of exogenous TAG is represented by a first order process. The endogenous production and removal of TAG from plasma are described with a turnover model. AZD7687 inhibits the contribution of exogenous TAG into circulation. One or two compartment models with first order absorption was used to describe the PK of AZD7687 for the different species. Nonlinear mixed effect mod

SUBMITTER: Morentin Gutierrez P 

PROVIDER: S-EPMC6408865 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature