Abstract
Background: Recently, pharmaceutical research has focused on in vitro-in vivo correlation as a novel challenge, and in silico modeling has been an important component. As in silico models are highly representative of practical use, regulatory agencies such as the US Food and Drug Administration and European Medicines Agency have recognized and utilized in silico modeling as a useful tool; this allows pharmaceutical organizations to use Physiologically Based Pharmacokinetic (PBPK) models for decision-making, which may aid the financial efficiency of a clinical trial. However, some studies have shown differences of up to approximately 40% in pharmacokinetic parameters such as area under the curve or maximum serum concentration between observed and simulated data.
Methods: Gastroplus™ was used to demonstrate current PBPK simulation. 46 research papers were compared with each other's applications of PBPK simulation.
Results: To improve the accuracy of simulation, additional factors may need to be considered, such as precise volume of gastrointestinal sections, specific metabolism of the target drug, and physicochemical data of drug metabolites. Furthermore, the results of these simulations would be extremely valuable to the relevant applications. Simulation programs using Advanced Compartmental Absorption and Transit (ACAT)/PBPK modeling could be a powerful tool for companies performing pre-clinical experiments, and could provide a solution for the ethical issues and economic constraints of clinical trials.
Conclusion: If in silico modeling produced more precise results that could closely match clinical data, it could be more readily used to screen drug pharmacodynamics in bodily systems, and the efficiency of clinical trials would be improved. However, simulation programs are currently limited in their accuracy of pharmacodynamic predictions. In developing new drugs, pharmaceutical companies should address this issue in order to improve in silico/PBPK modeling in the future.
Keywords: In silico, PBPK model, ACAT model, PKPD-correlation, metabolite, intestinal metabolism, Gastroplus, IVIVC.
Graphical Abstract
Current Drug Metabolism
Title:In Vitro-In Vivo Correlation Using In Silico Modeling of Physiological Properties, Metabolites, and Intestinal Metabolism
Volume: 18 Issue: 11
Author(s): Sung-min Choi, Chin-Yang Kang, Beom-Jin Lee and Jun-Bom Park*
Affiliation:
- College of Pharmacy, Sahmyook University, Seoul 139-742,Korea
Keywords: In silico, PBPK model, ACAT model, PKPD-correlation, metabolite, intestinal metabolism, Gastroplus, IVIVC.
Abstract: Background: Recently, pharmaceutical research has focused on in vitro-in vivo correlation as a novel challenge, and in silico modeling has been an important component. As in silico models are highly representative of practical use, regulatory agencies such as the US Food and Drug Administration and European Medicines Agency have recognized and utilized in silico modeling as a useful tool; this allows pharmaceutical organizations to use Physiologically Based Pharmacokinetic (PBPK) models for decision-making, which may aid the financial efficiency of a clinical trial. However, some studies have shown differences of up to approximately 40% in pharmacokinetic parameters such as area under the curve or maximum serum concentration between observed and simulated data.
Methods: Gastroplus™ was used to demonstrate current PBPK simulation. 46 research papers were compared with each other's applications of PBPK simulation.
Results: To improve the accuracy of simulation, additional factors may need to be considered, such as precise volume of gastrointestinal sections, specific metabolism of the target drug, and physicochemical data of drug metabolites. Furthermore, the results of these simulations would be extremely valuable to the relevant applications. Simulation programs using Advanced Compartmental Absorption and Transit (ACAT)/PBPK modeling could be a powerful tool for companies performing pre-clinical experiments, and could provide a solution for the ethical issues and economic constraints of clinical trials.
Conclusion: If in silico modeling produced more precise results that could closely match clinical data, it could be more readily used to screen drug pharmacodynamics in bodily systems, and the efficiency of clinical trials would be improved. However, simulation programs are currently limited in their accuracy of pharmacodynamic predictions. In developing new drugs, pharmaceutical companies should address this issue in order to improve in silico/PBPK modeling in the future.
Export Options
About this article
Cite this article as:
Choi Sung-min , Kang Chin-Yang , Lee Beom-Jin and Park Jun-Bom *, In Vitro-In Vivo Correlation Using In Silico Modeling of Physiological Properties, Metabolites, and Intestinal Metabolism, Current Drug Metabolism 2017; 18 (11) . https://dx.doi.org/10.2174/1389200218666171031124347
DOI https://dx.doi.org/10.2174/1389200218666171031124347 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
AMP-Activated Protein Kinase and Type 2 Diabetes
Current Medicinal Chemistry Endothelial Endocytic Pathways: Gates for Vascular Drug Delivery
Current Vascular Pharmacology Mucoadhesive Polymers for Oral Transmucosal Drug Delivery: A Review
Current Pharmaceutical Design Intervention and Observational Trials are Complementary in Metabolomics: Diabetes and the Oral Glucose Tolerance Test
Current Topics in Medicinal Chemistry The Potentials of Uncariae Ramulus Cum Uncis for the Treatment of Migraine: Targeting CGRP in the Trigeminovascular System
Current Neuropharmacology Free Radicals Generated by Post-Prandial Oxidative Burst in the Early Alterations of Vascular Contractility
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) CD44 - a New Cardiovascular Drug Target or Merely an Innocent Bystander?
Cardiovascular & Hematological Disorders-Drug Targets Evaluation of Specific Immune Responses to BoNT/A and Tetanus Toxoid in Patients Undergoing Treatment for Neurologic Disorders
Endocrine, Metabolic & Immune Disorders - Drug Targets The Crosstalk between Gut Inflammation and Gastrointestinal Disorders During Acute Pancreatitis
Current Pharmaceutical Design Cerium and Yttrium Oxide Nanoparticles and Nano-selenium Produce Protective Effects Against H2O2-induced Oxidative Stress in Pancreatic Beta Cells by Modulating Mitochondrial Dysfunction
Pharmaceutical Nanotechnology Small Molecule Inhibitors of PKCθ as Potential Antiinflammatory Therapeutics
Current Topics in Medicinal Chemistry Statins and Type 2 Diabetes Mellitus: An Update After 1 Year
Current Pharmaceutical Design Assessment of Circulating Biomarkers in Relation to Various Stages of Diabetic Retinopathy in Type 2 Diabetic Patients-A Cross Sectional Study
Current Diabetes Reviews Selected Recent Advances in the Synthesis of Bioactive Compounds Using Olefin Metathesis as a Key Step
Current Organic Chemistry Metabolic Syndrome, Dyslipidemia and Regulation of Lipoprotein Metabolism
Current Diabetes Reviews Vitamin D Supplementation: A Promising Approach for the Prevention and Treatment of Strokes
Current Drug Targets Caenorhabditis elegans: A Model for Studying Human Pathogen Biology
Recent Patents on Biotechnology Recent Patents on Biomedical Applications for the Treatment of Atherosclerosis
Recent Patents on Regenerative Medicine Sirolimus: A Novel Immunosuppressive Drug in Heart Transplantation
Recent Patents on Cardiovascular Drug Discovery Editorial (Thematic Issue: From Multiple Hits to Multiple Therapeutic Targets of Non-alcoholic Fatty Liver Disease)
Current Drug Targets