ArticleThe AAPS journal2009
Prediction of modified release pharmacokinetics and pharmacodynamics from in vitro, immediate release, and intravenous data.
Article in The AAPS journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Nanoformulations in epilepsy therapy - a systematic review of emerging strategies in status epilepticus.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2025Pooled it
- Clinical Pharmacokinetics of Metoprolol: A Systematic Review.Clinical pharmacokinetics · 2022Pooled it
- Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability.Drug design, development and therapy · 2017Trial
- PXR polymorphisms and their impact on pharmacokinetics/pharmacodynamics of repaglinide in healthy Chinese volunteers.European journal of clinical pharmacology · 2013Trial
- Clinical pharmacokinetics of buffered propranolol sublingual tablet (Promptol™)-application of a new "physiologically based" model to assess absorption and disposition.The AAPS journal · 2013Trial
- A semi-mechanistic modeling strategy to link in vitro and in vivo drug release for modified release formulations.Pharmaceutical research · 2012Trial
- Application of New Approach Methodologies to Improve Oral Biopharmaceutic Assessments.Pharmaceutics · 2026Review
- Establishing the Human Duodenum Chip as a Surrogate for Effective Human Permeability: In Vitro and In Silico Assessment.The AAPS journal · 2025Article
- Surge DosePharmaceutics · 2025Article
- A physiologically based pharmacokinetic (PBPK) model describing the kinetics of a commercial mixture α-, β-, and γ-hexabromocyclododecane exposure in mice.Archives of toxicology · 2025Article
- Application of Physiologically-Based Pharmacokinetic (PBPK) Model in Drug Development and in Dietary Phytochemicals.Current pharmacology reports · 2025Review
- Physiologically Based Pharmacokinetic Model To Predict Metoprolol Disposition in Healthy and Disease Populations.ACS omega · 2023Article
- IVIVE: Facilitating the Use ofToxics · 2022Review
- Development of Extended-Release Mini-Tablets Containing Metoprolol Supported by Design of Experiments and Physiologically Based Biopharmaceutics Modeling.Pharmaceutics · 2022Article
- Budding Multi-matrix Technology-a Retrospective Approach, Deep Insights, and Future Perspectives.AAPS PharmSciTech · 2021Review
- A PBPK model describing the pharmacokinetics of γ-HBCD exposure in mice.Toxicology and applied pharmacology · 2021Article
- High-throughput PBTK models forExpert opinion on drug metabolism & toxicology · 2021Review
- Physiologically Based Biopharmaceutics Modeling of Regional and Colon Absorption in Dogs.Molecular pharmaceutics · 2021Article
- Use of Physiologically Based Pharmacokinetic (PBPK) Modeling for Predicting Drug-Food Interactions: an Industry Perspective.The AAPS journal · 2020Article
- Mechanistic Deconvolution of Oral Absorption Model with Dynamic Gastrointestinal Fluid to Predict Regional Rate and Extent of GI Drug Dissolution.The AAPS journal · 2019Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of this study was to demonstrate the value of mechanistic simulations in gaining insight into the behaviors of modified release (MR) formulations in vivo and to use the properly calibrated models for prediction of pharmacokinetics (PK) and pharmacodynamics (PD). GastroPlus (Simulations Plus, Inc.) was used to fit mechanistic models for adinazolam and metoprolol that describe the absorption, PK, and PD after intravenous (i.v.) and immediate release (IR) oral (p.o.) administration. The fitted model for adinazolam was then used to predict the PD profile for a MR formulation and to design a new formulation with desired onset and duration of action. The fitted metoprolol model was used to gain insight and to explain the in vivo behaviors of MR formulations. For each drug, a single absorption/PK model was fitted that provided simulated plasma concentration-time profiles closely matching observed in vivo profiles across several different i.v. and p.o doses. Sedation score profiles of adinazolam were fitted with an indirect PD model. For metoprolol, the fitted absorption/PK model for IR p.o. doses was used to select in vitro dissolution conditions that best matched the in vivo release of MR doses. This model also explained differences in exposure after administration of MR formulations with different release rates. Mechanistic absorption/PK models allow for detailed descriptions of all processes affecting the two drugs' bioavailability, including release/dissolution, absorption, and intestinal and hepatic first pass extraction. The insights gained can be used to design formulations that more effectively overcome identified problems.
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Registered trials
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