ArticlePharmaceutics2021
Mechanistic PBPK Modelling to Predict the Advantage of the Salt Form of a Drug When Dosed with Acid Reducing Agents.
Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Insights into Drug Absorption Impairment Mechanisms in Hepatic Impairment using Physiologically-based Pharmacokinetic Modelling: A Case Study with Nilotinib.The AAPS journal · 2026Article
- Optimization of Bottom-Up PBPK Model Development in SIMCYP via Retrospective Analysis of Clinical Human PK Data.Clinical and translational science · 2025Article
- Formulation Strategy of BCS-II Drugs by Coupling Mechanistic In-Vitro and Nonclinical In-Vivo Data with PBPK: Fundamentals of Absorption-Dissolution to Parameterization of Modelling and Simulation.AAPS PharmSciTech · 2025Review
- PBBM Considerations for Base Models, Model Validation, and Application Steps: Workshop Summary Report.Molecular pharmaceutics · 2024Review
- Model-Informed Drug Development: In Silico Assessment of Drug Bioperformance following Oral and Percutaneous Administration.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Assessing Dose-Exposure-Response Relationships of Miltefosine in Adults and Children using Physiologically-Based Pharmacokinetic Modeling Approach.Pharmaceutical research · 2023Article
- Integrating In Vitro Biopharmaceutics into Physiologically Based Biopharmaceutic Model (PBBM) to Predict Food Effect of BCS IV Zwitterionic Drug (GSK3640254).Pharmaceutics · 2023Article
- Physiologically Based Pharmacokinetics Modeling in Biopharmaceutics: Case Studies for Establishing the Bioequivalence Safe Space for Innovator and Generic Drugs.Pharmaceutical research · 2023Review
- Current State and Challenges of Physiologically Based Biopharmaceutics Modeling (PBBM) in Oral Drug Product Development.Pharmaceutical research · 2023Review
- Applications, Challenges, and Outlook for PBPK Modeling and Simulation: A Regulatory, Industrial and Academic Perspective.Pharmaceutical research · 2022Review
- Application of a Physiologically Based Pharmacokinetic Approach to Predict Theophylline Pharmacokinetics Using Virtual Non-Pregnant, Pregnant, Fetal, Breast-Feeding, and Neonatal Populations.Frontiers in pediatrics · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acid reducing agents (ARAs) reduce the dissolution rate of weakly basic drugs in the stomach potentially leading to lower bioavailability. Formulating the API as a rapidly dissolving salt is one strategy employed to reduce the impact of ARAs on dissolution of such drugs. In the present work, a model drug was selected with an immediate release formulation of the free base dosed in both the absence and presence of the ARA famotidine. In the latter case, bioavailability is restricted and several salt formulations were investigated. To simulate these drug products a mechanistic physiologically based pharmacokinetic (PBPK) model was built using the Simcyp Simulator, which illustrates the advantage of formulating an API as a salt compared to the free base form. The simulations use a mechanistic salt model utilising knowledge of the solubility product which was applied to predict the salt advantage. The developed PBPK model exemplifies that it can be critical to account for the surface pH and solubility when modelling the dissolution of low pKa bases and their salts in the gastric environment. In particular, the mechanistic salt model can be used to aid in screening and salt form selection where the aim is to mitigate effects of ARAs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.