Abstract
Quantitative human pharmacokinetic (PK) predictions play a critical role in assessing the quality of potential drug candidates and in selecting a human starting dose for clinical evaluation, where the parameters of clearance, volume of distribution, and bioavailability as well as the plasma concentration time profiles are the desired endpoints. While there are numerous reports validating the use of different methods for predictions, it still remains an open question as to what animal species to include when extrapolating the animal PK to human. Given toxicological assessment is generally conducted in two species, a rodent and a non-rodent species, prior to evaluation in human subjects, rat, dog and/or monkey are typically the species ADME scientists employ to evaluate PK. However, the question is, can we achieve an adequate prediction without the use of larger species such as monkey? In the end, the data and tools utilized for human PK predictions will depend on a number of factors such as information from observed human PK for structurally related compounds, the primary mechanism of clearance, and the availability of in silico and in vitro tools applicable to the respective clearance mechanism. Despite these dependencies, for most situations, adequate predictions can be achieved without the use of monkey PK for predicting human.
Keywords: Clearance, PBPK, pharmacokinetics, prediction, scaling, in vitro, in silico
Current Topics in Medicinal Chemistry
Title: Drug Design Tools - In Silico, In Vitro and In Vivo ADME/PK Prediction and Interpretation: Is PK in Monkey An Essential Part of a Good Human PK Prediction?
Volume: 11 Issue: 4
Author(s): Natilie A. Hosea
Affiliation:
Keywords: Clearance, PBPK, pharmacokinetics, prediction, scaling, in vitro, in silico
Abstract: Quantitative human pharmacokinetic (PK) predictions play a critical role in assessing the quality of potential drug candidates and in selecting a human starting dose for clinical evaluation, where the parameters of clearance, volume of distribution, and bioavailability as well as the plasma concentration time profiles are the desired endpoints. While there are numerous reports validating the use of different methods for predictions, it still remains an open question as to what animal species to include when extrapolating the animal PK to human. Given toxicological assessment is generally conducted in two species, a rodent and a non-rodent species, prior to evaluation in human subjects, rat, dog and/or monkey are typically the species ADME scientists employ to evaluate PK. However, the question is, can we achieve an adequate prediction without the use of larger species such as monkey? In the end, the data and tools utilized for human PK predictions will depend on a number of factors such as information from observed human PK for structurally related compounds, the primary mechanism of clearance, and the availability of in silico and in vitro tools applicable to the respective clearance mechanism. Despite these dependencies, for most situations, adequate predictions can be achieved without the use of monkey PK for predicting human.
Export Options
About this article
Cite this article as:
A. Hosea Natilie, Drug Design Tools - In Silico, In Vitro and In Vivo ADME/PK Prediction and Interpretation: Is PK in Monkey An Essential Part of a Good Human PK Prediction?, Current Topics in Medicinal Chemistry 2011; 11 (4) . https://dx.doi.org/10.2174/156802611794480954
DOI https://dx.doi.org/10.2174/156802611794480954 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- 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