Safety Pharmacology in Pharmaceutical Development Approval and Post Marketing Surveillance, Second Edition

Safety Pharmacology: Background, History, Issues, and ConcernsGeneral versus safety pharmacology

History

Reasons for poor predictive performance

Why tiers

Study designs and principles

Issues

Integral versus separate

Regulatory requirements

Regulatory Requirements: ICH, FDA, EMA, and Japan

Introduction

Principles of Screening and Study Design

Characteristics of screens

Uses of screens

Types of screens

Criterion: Development and use

Analysis of screening data

Study design

References

Introduction

Cardiovascular System

History

Summary

Core battery CNS procedures

Central Nervous System

Rat

Dog

Sleep induction and interaction with hypnotics

Higher cognitive function

Isolated tissue assays

CNS function: Electroencephalography

Neurochemical and biochemical assays

Plethysmography

Respiratory System

Design of respiratory function safety studies

Study design considerations

Major functions of the kidney

Renal Function

Acute renal failure

Functional reserve of the kidney

Clearance

Free water clearance and renal concentrating ability

Clinical chemistry measures

Animal models

Examples of species differences in drug sensitivity

Drug-induced alterations of GI transit or motility

The Gastrointestinal System

Gastrointestinal function

Assessment of intestinal transit

Determination of intestinal absorption

Gastric emptying rate and gastric pH changes: A new model

Effects of drugs on gut immune system (jejunum, ileum, colon)

Candidate drugs to evaluate for effects on gut immune system

Conclusions

Introduction to the immune system and adverse modulation activities of drugs

The Immune System

Overview of the immune system

Immunotoxic effects