Abstract
This review focuses on a discussion of the controversies in allometric scaling (AS) for predicting human clearance from a mathematical and statistical perspective. First, a history of allometric scaling in comparative biology and its use in pharmacokinetics are reviewed. It is shown that the application of AS in predicting human clearance values based on a limited number of animal species (typically, 3 or 4) contains fundamental statistical errors from when AS was first introduced from comparative biology. Second, the mathematical nature of various allometrically-based methods is revealed and the soundness of these methods is assessed. It is demonstrated that any of these methods, which incorporate a correction factor in a traditional allometric approach (varying-exponent allometry), not only reduces the statistical power of the allometric analysis, but are also incorrect with regard to aspects of biology. Finally, it is concluded that allometry remains a valuable tool for predicting human clearance, and should be applied in the context of a fixed exponent. However, fixed-exponent allometry does not provide satisfactory accuracy in predicting human clearance, since it is not able to capture the biological differences among species. Therefore, it is recommended that the overall effort in predicting human pharmacokinetics should be directed to the collection and generation of reliable data (both in vitro and in vivo) along with a better understanding of the DMPK properties of the chemical entity.
Keywords: Clearance, fixed-exponent allometry, varying-exponent allometry, in vitro-in vivo extrapolation
Current Topics in Medicinal Chemistry
Title: Controversies in Allometric Scaling for Predicting Human Drug Clearance: An Historical Problem and Reflections on What Works and What Does Not
Volume: 11 Issue: 4
Author(s): Huadong Tang and Michael Mayersohn
Affiliation:
Keywords: Clearance, fixed-exponent allometry, varying-exponent allometry, in vitro-in vivo extrapolation
Abstract: This review focuses on a discussion of the controversies in allometric scaling (AS) for predicting human clearance from a mathematical and statistical perspective. First, a history of allometric scaling in comparative biology and its use in pharmacokinetics are reviewed. It is shown that the application of AS in predicting human clearance values based on a limited number of animal species (typically, 3 or 4) contains fundamental statistical errors from when AS was first introduced from comparative biology. Second, the mathematical nature of various allometrically-based methods is revealed and the soundness of these methods is assessed. It is demonstrated that any of these methods, which incorporate a correction factor in a traditional allometric approach (varying-exponent allometry), not only reduces the statistical power of the allometric analysis, but are also incorrect with regard to aspects of biology. Finally, it is concluded that allometry remains a valuable tool for predicting human clearance, and should be applied in the context of a fixed exponent. However, fixed-exponent allometry does not provide satisfactory accuracy in predicting human clearance, since it is not able to capture the biological differences among species. Therefore, it is recommended that the overall effort in predicting human pharmacokinetics should be directed to the collection and generation of reliable data (both in vitro and in vivo) along with a better understanding of the DMPK properties of the chemical entity.
Export Options
About this article
Cite this article as:
Tang Huadong and Mayersohn Michael, Controversies in Allometric Scaling for Predicting Human Drug Clearance: An Historical Problem and Reflections on What Works and What Does Not, Current Topics in Medicinal Chemistry 2011; 11 (4) . https://dx.doi.org/10.2174/156802611794480945
DOI https://dx.doi.org/10.2174/156802611794480945 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |

- 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
-
Risk Factors, CD4 Long-Term Evolution and Mortality of HIV-Infected Patients who Persistently Maintain Low CD4 Counts, Despite Virological Response to HAART
Current HIV Research A Discussion Regarding the Application of the Hertz Contact Theory on Biological Samples in AFM Nanoindentation Experiments
Micro and Nanosystems Pharmacokinetic and Pharmacodynamic Relationship of Blinatumomab in Patients with Non-Hodgkin Lymphoma
Current Clinical Pharmacology The Use of Nitric Oxide Synthase Inhibitors in Inflammatory Diseases: A Novel Class of Anti-Inflammatory Agents
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Changing Pain Management Strategy from Opioid-centric Towards Improve Postoperative Cognitive Dysfunction with Dexmedetomidine
Current Drug Metabolism Current and Emerging Therapies in Neuroendocrine Tumors: Impact of Genetic Targets on Clinical Outcomes
Clinical Cancer Drugs QSAR and Complex Network Recognition of miRNAs in Stem Cells
Current Bioinformatics Activated Cancer Therapy Using Light and Ultrasound - A Case Series of Sonodynamic Photodynamic Therapy in 115 Patients Over a 4 Year Period
Current Drug Therapy The Effect of Sex Education and Counseling on the Sexual Function of Iranian Reproductive Age Women: A Systematic Review and Meta-Analysis
Current Women`s Health Reviews Nardilysin, A Basic Residues Specific Metallopeptidase That Mediates Cell Migration and Proliferation
Protein & Peptide Letters Systematic Review and Quality Appraisal of International Guidelines on Perinatal Care of Extremely Premature Infants
Current Pediatric Reviews Annotation of the Human Genome by High-Throughput Sequence Analysis of Naturally Occurring Proteins
Current Proteomics Small-molecule Antiviral Agents in Ongoing Clinical Trials for COVID-19
Current Drug Targets Consumption of Cooked Navy Bean Powders Modulate the Canine Fecal and Urine Metabolome
Current Metabolomics Studies on the Pathophysiology and Genetic Basis of Migraine
Current Genomics Mucosal Vaccines: Where Do We Stand?
Current Topics in Medicinal Chemistry Cellular Localisation of Chromogranins and Processed Products in the Diffuse Neuroendocrine System and Related Tumours
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Targeting Inflammatory Bowel Diseases by Nanocarriers Loaded with Small and Biopharmaceutical Anti-Inflammatory Drugs
Current Pharmaceutical Design A Practical Approach to Diagnosis and Treatment of Symptomatic Thromboembolic Events in Children with Acute Lymphoblastic Leukemia: Recommendations of the “Coagulation Defects” AIEOP Working Group
Recent Patents on Cardiovascular Drug Discovery Stem Cells Therapies in Basic Science and Translational Medicine: Current Status and Treatment Monitoring Strategies
Current Pharmaceutical Biotechnology