Pharmacokinetics and Pharmacodynamics of Biotech Drugs covers the basics, including the pharmacokinetics of peptides, monoclonal antibodies, antisense oligonucleotides, as well as viral and non-viral gene delivery vectors.

Features:

• Discusses such challenges and opportunities as pulmonary delivery of proteins and peptides, and the delivery of oligonucleotides
• Considers the integration of PK and PD concepts into the biotech drug development plan, taking as case studies the preclinical and clinical drug development of tasidotin, as well as the examples of cetuximab and pegfilgrastim

Contents

The Role of Pharmacokinetics and Pharmacodynamics in the Development of Biotech Drugs

• Biotech Drugs and the Pharmaceutical Industry
• Pharmacokinetics and Pharmacodynamics in Drug Development
• PK and PK/PD Pitfalls for Biotech Drugs
• Regulatory Guidance

Pharmacokinetics of Peptides and Proteins

• Administration Pathways
• Administration Route and Immunogenicity
• Distribution
• Elimination
• Interspecies Scaling

Pharmacokinetics of Monoclonal Antibodies

• The Human Immune System
• Physiological Antibodies
• Therapeutic Antibodies
• Effector Functions and Modes of Action of Antibodies
• Prerequisites for mAb Therapy
• Issues in the Bioanalysis of Antibodies
• Catabolism of Antibodies
• Pharmacokinetic Characteristics of mAbs
• Pharmacokinetic Modeling of mAbs
• Pharmacodynamics of mAbs

Pharmacokinetics and Pharmacodynamics of Antisense Oligonucleotides

• Pharmacokinetics
• Pharmacodynamics

Pharmacokinetics of Viral and Non-Viral Gene Delivery Vectors

• Anatomical Considerations
• Naked DNA
• Non-Viral Vectors
• Viral Vectors

Bioanalytical Methods Used for Pharmacokinetic Evaluations of Biotech Macromolecule Drugs: Issues, Assay Approaches, and Limitations

• Bioanalytical Methods for Macromolecule Drug Analysis: Common Considerations
• The Bioanalytical Method Workhorses
• Case Studies

Limitations of Noncompartmental Pharmacokinetic Analysis of Biotech Drugs

• The Concept of Volume of Distribution
• Calculation of Vss
• Pitfalls in Calculating Vss

Bioequivalence of Biologics

• Prevailing Opinion: Science, Economics, and Politics
• Biologics: Time Course of Immunogenicity
• Pharmaceutical Equivalence
• Bioequivalence: Metrics and Methods for Biologics
• Case Study: Low-Molecular-Weight Heparins

Biopharmaceutical Challenges: Pulmonary Delivery of Proteins and Peptides

• Structure and Physiology of the Pulmonary System
• Barriers to Pulmonary Absorption of Peptides and Proteins
• Strategies for Pulmonary Delivery
• Experimental Models
• Pulmonary Delivery of Peptides and Proteins
• Limitations of Aerosol Delivery

Biopharmaceutical Challenges: Delivery of Oligonucleotides

• ASOs: The Physico-Chemical Properties
• Local Administration
• Systemic Delivery

Custom-Tailored Pharmacokinetics and Pharmacodynamics via Chemical Modifications of Biotech Drugs

• Polymers Used in Biotechnological Drug PEGylation
• Advantages of PEG as Drug Carrier
• Chemical Aspects Critical for the Pharmacokinetics of Drug Conjugates
• Insulin
• Interferons
• Avidin
• Non-Peptide Drug Conjugation

Exposure–Response Relationships for Therapeutic Biologic Products

• Hormones
• Cytokines
• Growth Factors
• Soluble Receptors
• Monoclonal Antibodies (mAbs)

Preclinical and Clinical Drug Development of Tasidotin, a Depsi-Pentapeptide Oncolytic Agent

• The Dolastatins
• Discovery and Preclinical Pharmacokinetics of Tasidotin
• Preclinical Pharmacology of Tasidotin and ILX651-C-Carboxylate
• Toxicology of Tasidotin
• Clinical Pharmacology and Studies of Tasidotin in Patients with Solid Tumors
• Clinical Pharmacology of ILX651-C-Carboxylate
• Exposure–Response Relationships

Clinical Drug Development of Cetuximab, a Monoclonal Antibody

• Specific Considerations in Oncologic Drug Development
• Introduction to the Clinical Pharmacokinetics of Cetuximab
• Early Attempts to Characterize the PK of Cetuximab
• PK of Cetuximab Following Pooling of Data Across All Studies
• Characterization of Cetuximab PK by a Population PK Approach
• Drug–Drug Interaction Studies

Integration of Pharmacokinetics and Pharmacodynamics Into the Drug Development of Pegfilgrastim, a Pegylated Protein

• Overview of Filgrastim Pharmacokinetics
• The Making of Pegfilgrastim
• Preclinical Pharmacokinetics and Pharmacodynamics of Pegfilgrastim
• Pharmacokinetic and Pharmacodynamic Modeling
• Clinical Pharmacokinetics and Pharmacodynamics of Pegfilgrastim
• Basis for the Fixed-Dose Rationale
• Clinical Evaluation of the Fixed Dose

Index

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