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ADME is the key for ensuring efficacy and tolerability. However, many drugs still fail due to poor ADME. This report examines the latest research on the causes and consequences of ADME changes in the elderly and children.
Commercial considerations such as market size, demographics, and the impact of ADME on the cost of drug development are thoroughly discussed. In addition, age related changes in ADME and in silico ADME profiles are detailed. The Report features exclusive interviews with key opinion leaders in the ADME arena as well as relevant case studies.
TABLE OF CONTENTS
Chapter 1: Executive Summary
- References
Chapter 2: Background
- Introduction
- De.ning Age
- The Elderly
- Pediatric Groups
- Demographic Changes
- Healthcare Expenditure in the Elderly
- Age-Related Diseases: An Increasingly Important Market
- Regulatory Issues
- Regulatory Pressure to Study Pediatric Populations
- Exploratory Investigational New Drug Studies
- Increased Emphasis on Safety
- Biomarkers
- Sources of Information and Scope of Report
- References
Chapter 3: ADME𦝁he Essentials
- What is Pharmacokinetics?
- Absorption
- Transporters
- Distribution
- The Apparent Volume of Distribution (VD)
- Protein Binding
- Metabolism
- Pharmacogenomics and Metabolism
- Drug Transporters and Metabolism
- Excretion
- Variation
- The Problem of Poor Compliance
- Whole-Body Pharmacokinetic Modeling
- Receptor Microscopic Autoradiography
- Non-Linear Pharmacokinetics
- High-Throughput Screening and the Rule of Five
- References
Chapter 4: Age-related Changes in ADME
- Introduction
- Age-Related Physiological Changes in the Elderly that Impact on ADME
- Renal Excretion
- Hepatic Function
- Sources of Age-Related Changes in Children
- Juvenile Animal Studies
- Modi.ed Release and Other Formulation Issues
- Clinical Biomarkers
- References
Chapter 5: In Silico ADME
- Introduction
- Examples of In silico ADME
- Simulations Plus
- MetaDrug
- Lhasa Limited
- VolSurf
- Combinatorial Pharmacology
- PK-Sim
- A Lack of Data Hinders In silico Development
- Insights from Systems Biology
- QSAR and ADME
- References
Chapter 6: Expert Interviews
- Participants
- Questions
- References
Chapter 7: Commercial Considerations
- Introduction
- Market Size
- Impact on the Cost of Drug Development
- References
Chapter 8: Summary and Conclusions
Chapter 9: Company Pro.les
- Accelrys, Inc
- BASi (Bioanalytical Systems, Inc.)
- BioFocus
- Covance Inc.
- DDS Medicines Research Ltd.
- DxS Ltd .
- GeneGo Inc
- Kendle
- Lhasa Limited
- Molecular Devices Corporation
- Nimbus Biotechnologie GmbH
- NoAb BioDiscoveries Inc
- Oxford Genome Sciences (UK) Ltd
- Pharmaceutical Pro.les Group
- Pharmagene Laboratories Limited
- Simulations Plus, Inc
- Tripos, Inc
- References
Chapter 10: References
TABLE OF EXHIBITS
- Exhibit 2.1 Life Expectancy from Birth for Men and Women Born Between 1900 and 2000
- Exhibit 2.2 The Proportion of the Population Aged over 80 Years in Various Countries
- Exhibit 2.3 Healthcare Expenditure in the Elderly in Various Countries
- Exhibit 3.1 Idealized Plasma Concentration Time Curve Showing Some Key Pharmacokinetic Parameters
- Exhibit 3.2 The Effect of SNP in Drug Metabolism Enzyme on the Plasma Concentration-time Curve for a Hypothetical Medicine
- Exhibit 3.3 Patients of Patients Intolerant of Simvastatin Strati.ed by Expression of CYP2D6
- Exhibit 3.4 Examples of SNPs in Drug Metabolizing Enzymes and the Allele Frequency in Various Populations
- Exhibit 3.5 Examples of Some Factors In.uencing Intra-patient Variations in Pharmacokinetics
- Exhibit 3.6 Compliance Rates in Various Conditions
- Exhibit 3.7 Examples of Modi.ed Release Formulations
- Exhibit 3.8 Drug-Target Homunculus
- Exhibit 4.1 The Effect of Age on Plasma Elimination Half-lives
- Exhibit 4.2 Factors that Could In.uence ADME in Preterm Infants and Neonates Born at Term
- Exhibit 4.3 Examples of Physiological Functions that May In.uence Pharmacokinetic Differences between Infants and Adults
- Exhibit 4.4 Body Composition in Neonates and Adults
- Exhibit 5.1 Clinical Data and GastroPlus Simulation for Oral Administration of Gabapentin to Pediatric Subjects with Average Age of 6 years
- Exhibit 5.2 Observed Clearance in Children versus Clearance as Predicted with PK-Sim
- Exhibit 5.3 Simulated Plasma Concentration Curves of Levo.oxacin and Morphine for Children for Different Age Groups Compared to the Corresponding Experimental Data
- Exhibit 5.4 A Hypothetical Example of a Network
- Exhibit 5.5 Types of QSAR Analyses .
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