Population Target-Mediated Pharmacokinetic/Pharmacodynamic Modeling to Evaluate SPI-62 Exposure and Hepatic 11β-Hydroxysteroid Dehydrogenase Type 1 (HSD-1) Inhibition in Healthy Adults.

ABSTRACT:

Introduction

SPI-62 is a small-molecule 11β-hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor exhibiting complicated nonlinear pharmacokinetics (PK) in human. Previously, we developed a target-mediated drug disposition (TMDD) model to characterize the substantial nonlinear PK of SPI-62.

Objective

The aim of the current analysis was to perform population PK/PD analysis to further link SPI-62 exposure (i.e., PK) with its response (i.e., inhibition of hepatic HSD-1 activity) to gain a quantitative understanding of the SPI-62 dose-exposure-response relationship.

Methods

PK and PD data from the first-in-human (FIH) clinical trials, including single ascending dose (SAD) and multiple ascending dose (MAD) studies, were used for model development. During the model developm

SUBMITTER: Wu N 

PROVIDER: S-EPMC10449972 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature