Accelerating Development of Benziamidazole-Class Proton Pump Inhibitors: A Mechanism-Based PK/PD Model to Optimize Study Design with Ilaprazole as a Case Drug.

ABSTRACT: Proton pump inhibitors (PPIs) are the mainstay for treatment of acid-related diseases. This study developed a mechanism-based pharmacokinetic (PK) and pharmacodynamics (PD) model with ilaprazole as case drug, so as to support and accelerate the development of novel PPIs. The model was established and verified using the PK and PD data from 26 subjects receiving 5 to 30 mg of ilaprazole and 22 subjects receiving the loading dose of ilaprazole 20 mg followed by 10 mg once daily for 2 days. The nonlinear mixed-effects modeling approach was performed for the PK/PD model. A two-compartment model with linear elimination and covariates (body weight and gender) described the observed data well. The relationship between plasma concentrations of ilaprazole and gastric acid pH was well quantified with

SUBMITTER: Jia R 

PROVIDER: S-EPMC7998456 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature