ArticleThe AAPS journal2014
Physiologically based absorption modelling to predict the impact of drug properties on pharmacokinetics of bitopertin.
Article in The AAPS journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification.Drug metabolism and disposition: the biological fate of chemicals · 2015Pooled it
- Physiologically Based Absorption Modeling to Explore the Impact of Food and Gastric pH Changes on the Pharmacokinetics of Alectinib.The AAPS journal · 2016Trial
- Effects of Cytochrome P450 3A4 Inhibitors-Ketoconazole and Erythromycin-on Bitopertin Pharmacokinetics and Comparison with Physiologically Based Modelling Predictions.Clinical pharmacokinetics · 2016Trial
- 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
- Pharmacokinetic profile of bitopertin, a selective GlyTNaunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Developing a Formulation Strategy Coupled with PBPK Modeling and Simulation for the Weakly Basic Drug Albendazole.Pharmaceutics · 2023Article
- The Use of Physiologically Based Pharmacokinetic Analyses-in Biopharmaceutics Applications -Regulatory and Industry Perspectives.Pharmaceutical research · 2022Review
- Optimization of Spray-Drying Parameters for Formulation Development at Preclinical Scale.AAPS PharmSciTech · 2021Article
- Use of Physiologically Based Pharmacokinetic (PBPK) Modeling for Predicting Drug-Food Interactions: an Industry Perspective.The AAPS journal · 2020Article
- Dissolution and Translational Modeling Strategies Toward Establishing an In Vitro-In Vivo Link-a Workshop Summary Report.The AAPS journal · 2019Article
- Progress in Prediction and Interpretation of Clinically Relevant Metabolic Drug-Drug Interactions: a Minireview Illustrating Recent Developments and Current Opportunities.Current pharmacology reports · 2017Review
- Physiologically-based pharmacokinetic models: approaches for enabling personalized medicine.Journal of pharmacokinetics and pharmacodynamics · 2016Review
- Combining 'Bottom-Up' and 'Top-Down' Methods to Assess Ethnic Difference in Clearance: Bitopertin as an Example.Clinical pharmacokinetics · 2016Article
- Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.The AAPS journal · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bitopertin (RG1678) is a glycine reuptake inhibitor in phase 3 trials for treatment of schizophrenia. Its clinical oral pharmacokinetics is sensitive to changes in drug substance particle size and dosage form. Physiologically based pharmacokinetic (PBPK) absorption model simulations of the impact of changes in particle size and dosage form (either capsules, tablets, or an aqueous suspension) on oral pharmacokinetics was verified by comparison to measured plasma concentrations. Then, a model parameter sensitivity analysis was applied to set limits on the particle sizes included in tablets for the market. The model was also used to explore the in vitro to in vivo correlation. Simulated changes in oral pharmacokinetics caused by differences in particle size and dosage form were confirmed in two separate relative bioavailability studies. Model parameter sensitivity analyses predicted that AUCinf was hardly reduced as long as particle diameter (D50) remained smaller than 30 μm, and >20% reduced Cmax is anticipated only when particle diameter exceeds 15 μm. An exploration of the sensitivity to the presence of larger particles within a polydisperse distribution showed that simulated Cmax is again more affected than AUC but is less than 20% reduced as long as D50 is less than 8 μm and D90 is smaller than 56 μm. PBPK absorption modelling can contribute to a quality by design (QbD) approach for clinical formulation development and support the setting of biorelevant specifications for release of the product.
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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.