Physiologically-based pharmacokinetic modeling for predicting drug-drug interactions induced by acid-reducing agents
10.16438/j.0513-4870.2021-0272
- VernacularTitle:生理药代动力学模型预测抑酸药物所致药物相互作用的研究进展
- Author:
Xiao-wen WANG
1
,
2
;
Qing-feng HE
3
;
Xiao-qiang XIANG
3
;
Bing HAN
1
Author Information
1. Central Hospital of Minhang Distract, Shanghai 201109, China
2. School of Pharmacy, Fudan University, Shanghai 201203, China
3. School of Pharmacy, Fudan University, Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
rug absorption;
physiologically based pharmacokinetic modeling;
rug-drug interaction
- From:
Acta Pharmaceutica Sinica
2021;56(8):2197-2203
- CountryChina
- Language:Chinese
-
Abstract:
Gastric pH is an important factor that affects drug absorption, as gastric pH may lead to lower bioavailability, especially for weak-base drugs. Acid-reducing agents (ARAs) such as antacids, histamine-2 receptor antagonists, and proton pump inhibitors, are susceptible to drug-drug interactions (DDIs), potentially resulting in the loss of efficacy. Physiologically based pharmacokinetic (PBPK) modeling is an important tool for the evaluation of oral drug-drug interactions and the most commonly used models include the advanced comparative absorption and transport (ACAT) model and the advanced dissolution, absorption and metabolism (ADAM) model. These models can be used for adjustment of the dosage regimen and the screening of candidate drugs in drug development by simulating the change of gastric pH to predict the change in drug absorption. This review summarizes the theoretical basis, the most common PBPK models used to predict drug absorption, and the effects of different kinds of ARAs drugs on gastric pH. Some successful applications of PBPK modeling in predicting the effects of gastric pH on drug absorption are also presented.
