Abstract
Glucuronidation has been recognized as an important clearance mechanism in humans. Therefore, knowledge about the contribution of glucuronidation to clearance of drug candidates is of great value in early drug development. In this article, we discuss the recent progress made to predict in vivo glucuronidation parameters (e.g., hepatic clearance, and intestinal availability) using in vitro data, which are readily obtained using microsomes and hepatocytes, so called “in vitro- in vivo extrapolation” (IVIVE). Of note the intrinsic clearances obtained from microsomal incubations in the presence of bovine serum albumin (BSA) provide accurate predictions of the in vivo clearances in addition to those from hepatocytes. Further, we describe the lack of correlation between cellular and microsomal production of glucuronide and provide possible reasons. Due to the high prediction accuracy, those who study in vitro glucuronidation are encouraged to map their data to in vivo using IVIVE strategy for more informative data interpretation.
Keywords: Drug metabolism, glucuronidation, UGTs, in vitro-in vitro extrapolation, in vitro-in vitro correlation, quantitative prediction.
Current Topics in Medicinal Chemistry
Title:Quantitative Prediction of Glucuronidation in Humans Using the In Vitro- In Vivo Extrapolation Approach
Volume: 13 Issue: 11
Author(s): Baojian Wu, Dong Dong, Ming Hu and Shuxing Zhang
Affiliation:
Keywords: Drug metabolism, glucuronidation, UGTs, in vitro-in vitro extrapolation, in vitro-in vitro correlation, quantitative prediction.
Abstract: Glucuronidation has been recognized as an important clearance mechanism in humans. Therefore, knowledge about the contribution of glucuronidation to clearance of drug candidates is of great value in early drug development. In this article, we discuss the recent progress made to predict in vivo glucuronidation parameters (e.g., hepatic clearance, and intestinal availability) using in vitro data, which are readily obtained using microsomes and hepatocytes, so called “in vitro- in vivo extrapolation” (IVIVE). Of note the intrinsic clearances obtained from microsomal incubations in the presence of bovine serum albumin (BSA) provide accurate predictions of the in vivo clearances in addition to those from hepatocytes. Further, we describe the lack of correlation between cellular and microsomal production of glucuronide and provide possible reasons. Due to the high prediction accuracy, those who study in vitro glucuronidation are encouraged to map their data to in vivo using IVIVE strategy for more informative data interpretation.
Export Options
About this article
Cite this article as:
Wu Baojian, Dong Dong, Hu Ming and Zhang Shuxing, Quantitative Prediction of Glucuronidation in Humans Using the In Vitro- In Vivo Extrapolation Approach, Current Topics in Medicinal Chemistry 2013; 13 (11) . https://dx.doi.org/10.2174/15680266113139990038
DOI https://dx.doi.org/10.2174/15680266113139990038 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
- Author Guidelines
- 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
-
Meet Our Editorial Board Member
Current Proteomics Extracellular Vesicles in the Treatment of Parkinson’s Disease: A Review
Current Medicinal Chemistry The Progress of Selective Fluorescent Chemosensors by Boronic Acid
Current Medicinal Chemistry Improving DNA Vaccine Performance Through Vector Design
Current Gene Therapy Calreticulin is Differentially Expressed in Invasive Ductal Carcinoma: A Comparative Study
Current Proteomics Antioxidant Properties of Hydroxycinnamic Acids: A Review of Structure- Activity Relationships
Current Medicinal Chemistry Effect of Nanotechnology Approaches on Anti-retroviral Molecule: Efavirenz
Current Organic Chemistry Pharmacological Targeting of the Hsp70 Chaperone
Current Topics in Medicinal Chemistry MicroRNAs and Peroxisome Proliferator-Activated Receptors Governing the Differentiation of Mesenchymal Stem Cells
Current Stem Cell Research & Therapy Changing Faces of Transcriptional Regulation Reflected by Zic3
Current Genomics The Immunohistochemical Assessment of HPV Related Adenocarcinoma: Pathologic and Clinical Prognostic Significance
Current Pharmaceutical Design Resveratrol Promotes HIV-1 Tat Accumulation <i>via</i> AKT/FOXO1 Signaling Axis and Potentiates Vorinostat to Antagonize HIV-1 Latency
Current HIV Research Hierarchical Profiles of Signaling Pathways and Networks Reveal Two Complementary Pharmacological Mechanisms
CNS & Neurological Disorders - Drug Targets Synthesis of Polynuclear Complexes with an Amino Acid or a Peptide as a Bridging Ligand
Current Chemical Biology Synthesis of pyridyl benzimidazoles encompassing 4-thiazolidinone derivatives as potential antimicrobial agents
Letters in Drug Design & Discovery Therapeutic Targeting of TRP Channels - The TR(i)P to Pain Relief
Current Topics in Medicinal Chemistry Challenges in Mass Spectrometry Based Targeted Metabolomics
Current Molecular Medicine The Role of SNAP-tag in Technical Approaches
Current Pharmaceutical Design Quantitative Structure-Activity Relationships for Anticancer Activity of 2- Phenylindoles Using Mathematical Molecular Descriptors
Current Computer-Aided Drug Design Computer Aided Drug Design for Multi-Target Drug Design: SAR /QSAR, Molecular Docking and Pharmacophore Methods
Current Drug Targets