Textbook of Pharmaceutical Medicine.

Format:

Book

Author/Creator:

Griffin, John.

Contributor:

Grady, John.

Griffin, John P.

Language:

English

Subjects (All):

Ciencias sociales--Artículos--Publicaciones periódicas.

Ciencias sociales -- Artículos -- Publicaciones periódicas.

Social sciences--Periodicals.

Social sciences -- Periodicals.

Articulos--Publicaciones periodicas.

Articulos -- Publicaciones periodicas.

Libros electronicos.

Physical Description:

1 online resource (896 pages)

Edition:

4th ed.

Place of Publication:

London : Blackwell Publishing Ltd., 2002.

Summary:

This edition has totally revised chapters on drug regulation in the USA, with new contributor, Dr Peter Barton Hutt formerly FDA Special Counsel. New contributions regarding pharmaco-economics are covered in two new chapters.

Contents:

Intro

Contents

Contributors

Preface

Acknowledgements

The editors

Part I: Research and development

1: Discovery of new medicines

1.1 Introduction

1.2 Historical aspects

1.2.1 Early discoveries

1.3 Impact of new technology on drug discovery

1.3.1 Receptor subtypes

1.3.2 Genomics

1.3.3 Pharmacogenomics

1.3.4 Proteomics

1.3.5 Bioinformatics and data mining technologies

1.3.6 Combinatorial chemistry and high-throughput screening

1.3.6.1 Combinatorial synthesis

1.3.6.2 Library design

1.3.7 Structure-based drug design

1.3.8 Virtual screening

1.3.9 NMR, x ray and mass spectroscopic techniques

1.3.10 Pharmacokinetics

1.4 Examples of drug discovery

1.4.1 Receptor ligands (agonists and antagonists)

1.4.1.1 Early examples

1.4.1.2 Selective oestrogen receptor modulators (oestrogen antagonists and aromatase inhibitors)

1.4.1.3 LHRH agonists and antagonists

1.4.1.4 Somatostatin agonists and antagonists

1.4.1.5 Angiotensin agonists and antagonists (peptides and non-peptides)

1.4.1.6 Bombesin/neuromedin agonists and antagonists

1.4.1.7 Bradykinin agonists and antagonists

1.4.1.8 Cholecystokinin agonists and antagonists

1.4.1.9 Endothelin antagonists

1.5 Enzyme inhibitors

1.5.1 Converting enzyme inhibitors

1.5.2 Aspartyl protease (renin and HIV protease) inhibitors

1.5.2.1 Renin inhibitors

1.5.2.2 HIV protease inhibitors

1.5.3 Thrombin inhibitors (serine protease)

1.5.4 Ras protein farnesyltransferase inhibitors

1.5.5 Protein kinase inhibitors

1.6 Protein-protein interaction inhibitors

1.6.1 a4ß1 and a5ß1 antagonists

1.7 Summary

References

2: Pharmaceutical development

2.1 Introduction

2.2 Preformulation

2.2.1 Structure determination

2.2.2 Analytical development

2.2.3 Salt form

2.2.4 Chemical stability.

2.2.5 Physicochemical properties

2.2.6 Chiral properties

2.2.7 Biopharmaceutical properties

2.2.8 Physical properties of the solid drug

2.2.9 Excipient compatibility

2.3 Formulation

2.3.1 Liquid formulations

2.3.2 Semi-solid formulations

2.3.3 Solid formulations

2.3.4 Contemporary formulationsa

2.3.5 Packaging

2.3.6 Stability testing

2.3.7 Scale-up and manufacture

2.3.8 Bioequivalence

2.4 Clinical trial supplies

2.4.1 Blinding

2.4.2 Labelling of clinical trial materials

2.4.3 Quality assurance of clinical trial supplies

2.5 Conclusions

Further reading

3: Toxicity testing

3.1 Introduction

3.1.2 The drug development process

3.1.3 Risk benefit

3.2 Preclinical safety pharmocology

3.2.1 Introduction

3.2.2 Regulatory guidelines

3.2.3 General considerations

3.2.4 Experimental design

3.2.4.1 Controls

3.2.4.2 Route

3.2.4.3 Dose levels in vivo

3.2.4.4 Dose levels in vitro

3.2.5 Safety pharmacology core battery

3.2.5.1 Central nervous system

3.2.5.2 Cardiovascular system

3.2.5.3 Respiratory system

3.2.5.4 Supplementary safety pharmacology studies

3.3 Single-dose studies

3.3.1 Study design

3.3.1.1 Preliminary studies

3.3.1.2 Definitive studies

3.4 Repeat-dose studies

3.4.1 The maximum repeatable dose (MRD) study

3.4.2 Definitive repeat-dose toxicity studies

3.4.2.1 Study interpretation

3.5 Oncogenicity studies

3.5.1 Route of administration

3.5.2 Dose selection

3.5.3 Group sizes

3.5.4 Conduct of study

3.5.5 Duration of study

3.5.6 Autopsy and microscopic examination

3.5.7 Evaluation of results

3.6 Reproductive toxicology

3.6.1 Aims of studies

3.6.1.1 General reproductive effects

3.6.1.2 Developmental effects

3.6.2 Types of studies

3.6.3 Timing of studies.

3.6.4 Juvenile toxicity studies

3.6.5 Evaluation and interpretation of data

3.6.5.1 Antifertility effects in the male

3.6.5.2 Antifertility effects in females

3.6.5.3 Teratogenesis

3.6.5.4 Postnatal effects

3.7 Genotoxicity testing

3.7.1 Study design

3.7.1.1 Bacterial tests for gene mutation

3.7.1.2 Assays for chromosomal aberrations

3.7.1.3 Mammalian cell tests for gene mutation

3.7.1.4 Detection of chromosome damage in rodent bone marrow using the micronucleus test

3.7.1.5 Unscheduled DNA synthesis (UDS) - ex vivo assay in rodent liver

3.7.2 Germ cell tests

3.7.3 Study interpretation

3.8 Irritation and sensitisation testing

3.8.1 Irritancy

3.8.1.1 Skin

3.8.1.2 Eye

3.8.2 Immunotoxicology

3.8.2.1 Sensitisation

3.8.2.2 Immunosuppression

3.8.3 Special routes

3.8.3.1 Intramuscular

3.8.3.2 Inhalation

3.8.3.3 Topical

3.8.3.4 Intrarectal

3.8.3.5 Intra-arterial

3.9 Animal numbers, costs and ethics

4: Exploratory development

4.1 Introduction

4.2 Planning exploratory development

4.2.1 The need for a regulatory strategy

4.2.2 Devising the plan

4.2.3 Presentation of the plan

4.3 Requirements for administration of an NAS to humans

4.3.1 Evidence of primary pharmacodynamic activity

4.3.2 Secondary pharmacodynamic activity and safety pharmacology

4.3.3 Pharmacokinetics and drug metabolism

4.3.4 Toxicology

4.3.5 Pharmaceutical formulations

4.4 The transfer from preclinical to clinical

4.4.1 Collaboration

4.4.2 Preparation of the clinical investigator's brochure

4.4.3 Aspects of the first protocol and ethics review

4.5 Studies in healthy volunteers

4.5.1 What is a healthy (non-patient) volunteer?

4.5.2 Why use healthy volunteers?

4.5.3 The regulatory position.

4.5.4 Source of healthy volunteers

4.5.5 Facilities and staff

4.5.6 Recruitment procedures

4.5.7 Good clinical practice

4.5.8 Adverse reactions in volunteer studies

4.5.9 Insurance and compensation

4.6 Study objectives in exploratory development

4.6.1 Tolerability and safety

4.6.2 Pharmacokinetics

4.6.3 Pharmacodynamics

4.7 Design of the first study in humans

4.7.1 Choice of dose range

4.7.2 Magnitude of dose increments

4.7.3 Should we dose to toxicity?

4.7.4 Number of doses for individual subjects and interval between doses

4.7.5 Use of placebo

4.7.6 Blinding

4.7.7 Parallel groups or crossover

4.7.8 Size of cohorts

4.8 Minimising risk

4.9 Subsequent studies in healthy volunteers

4.9.1 Multiple doses

4.9.2 Pharmacodynamics

4.9.3 Studies in the elderly

4.9.4 Drug and food interactions

4.9.5 Radiolabelled studies

4.10 Studies in patients

4.11 Outcomes of exploratory development

5: Clinical pharmacokinetics

5.1 Introduction

5.2 Basic concepts

5.2.1 Overview of the fate of administered drug

5.2.2 The plasma concentration-time curve

5.2.3 Descriptive versus conceptual parameters

5.2.3.1 Clearance

5.2.3.2 Bioavailability

5.2.3.3 Volume of distribution

5.2.3.4 Calculation of primary parameters

5.2.3.5 Half-life

5.2.4 Predictions from pharmacokinetic parameters

5.2.5 The use of pharmacokinetic information to design dosage regimens

5.3 Bioavailability and bioequivalence

5.3.1 Bioavailability

5.3.2 Bioequivalence

5.4 Drug interactions

5.4.1 Selection of studies

5.4.2 Study design

5.4.3 Enzyme induction and inhibition

5.4.4 Protein binding

5.5 The elderly

5.6 Renal impairment

5.7 Liver disease

5.8 Disposition, rates and routes of elimination of radiolabelled drug.

5.9 Pharmacokinetic-pharmacodynamic modelling

5.10 Population kinetics

5.11 The rest of the typical clinical pharmacokinetics package

5.12 The ideal drug from the point of view of pharmacokinetics

5.13 The role of pharmacokinetic properties in determining a dosage regimen

5.14 Summary

6: Clinical trials and good clinical practice

6.1 Introduction

6.1.1 The controlled clinical trial and pharmaceutical medicine

6.1.2 Concept of the controlled clinical trial

6.1.3 Types of clinical trial

6.1.4 Observational studies

6.1.5 Global implications

6.1.6 Good clinical practice (GCP)

6.1.6.1 Declaration of Helsinki

6.1.6.2 ICH GCP

6.1.6.3 EU Directive (2001/20/EC)

6.2 Basic ethical considerations

6.2.1 Peer review of proposed biomedical research

6.2.2 Informed consent

6.2.2.1 Notification to the general practitioner

6.2.2.2 Confidentiality

6.2.3 Pharmacogenetics

6.2.4 Studies in special groups

6.2.4.1 Paediatrics

6.2.4.2 Ethnic factors in clinical trial development

6.2.4.3 The elderly population

6.2.5 Compensation and insurance

6.2.6 The use of placebo

6.3 Preparation for the clinical trial

6.3.1 General considerations

6.3.2 Clinical trial design

6.3.2.1 Preparation for the clinical trial

6.3.2.2 Creating a hypothesis

6.3.2.3 Response variables

6.3.2.3.1 Efficacy endpoints

6.3.2.3.2 Safety endpoints

6.3.2.4 Patient population in trials and in clinical practice

6.3.2.5 Trial elements

6.3.2.5.1 Eligibility criteria

6.3.2.5.2 Bias

6.3.2.6 Choice of trial design

6.3.2.7 Pilot trials

6.3.2.8 Pivotal studies

6.3.2.9 Blindness

6.3.2.10 Controlled trial

6.3.2.11 Placebo

6.3.2.12 Comparator medicines

6.3.2.12.1 Parallel or crossover design

6.3.2.12.2 Dose selection.

6.3.2.12.3 Dose-response relationships, potency and efficacy.

Notes:

Description based on publisher supplied metadata and other sources.

Other Format:

Print version: Griffin, John Textbook of Pharmaceutical Medicine

ISBN:

9781405146067

OCLC:

437147416