About Book

Drug discovery and development are among the most important translational science activities that contribute to human health and well-being. Pharmaceuticals can be defined as drugs that prevent and cure disease. Drug development is the process of bringing a new drug molecule into clinical practice. In its broadest term, this encompasses all steps from the basic research process of finding a suitable molecular target to supporting the commercial launch of the drug. In a narrower sense, development refers only to the clinical parts of this process, with discovery used to describe the nonclinical research components; this topic is rich in jargon that is used in different ways by different companies and individuals. Many aspects of drug development focus on satisfying the regulatory requirements of drug licensing authorities. This book on pharmaceutical drug development encompasses an interdisciplinary study of the field that discusses the medicine industry, drug manufacturing processes. It provides significant information of this discipline to help develop a good understanding of this discipline and related fields. It deals with pharmacogenetics, drug interactions, drug delivery, drug monitoring, clinical pharmacology, drug/toxicant interactions and drug development. It includes some of the vital pieces of work being conducted across the world, on various topics related to pharmaceutical drug development. For students and researchers in the fields of pharmacology, hospital management, public health policy and pharmaceutical sciences, this book would prove to be very helpful.

Preface............................................................................................................v

Chapter 1 Application of Pharmacokinetics in Early Drug Development......1

Abstract...................................................................................................1

1. Introduction............................................................................................2

2. Pharmacokinetics and early drug development.............................3

3. Pharmacokinetic analyses....................................................................6

4. Nonclinical pharmacokinetics...........................................................11

5. Early clinical studies with primary endpoints of safety.............12

6. Early clinical studies with primary PK endpoints.......................16

7. Summary...............................................................................................19

Chapter 2 Circadian Clock Gene Expression and Drug/Toxicant Interactions as Novel Targets of Chronopharmacology and

Chronotoxicology......................................................................................24

Abstract.................................................................................................24

1. Introduction..........................................................................................25

2. Circadian rhythms affect Phase-I, Phase-II, and transporter gene

expressions in the liver......................................................................26

3. Circadian rhythm disruption affects therapeutic effects and

toxicity of xenobiotics in the liver...................................................28

4. Drugs/toxicants could affect both central and peripheral circadian

clock gene expression.........................................................................31

5. Drugs affect circadian clock gene expression as a novel target of

chronopharmacology..........................................................................32

6. Toxicants affect circadian clock gene expression as a novel target

of chronotoxicology............................................................................36

7. Summary and perspectives...............................................................37

Acknowledgements.............................................................................38

Conflict of interest..............................................................................38

Chapter 3 Clinical Pharmacology of Drugs Used in the Treatment of Patients

with Peptic Ulcer.......................................................................................46

1. Primary (genuine) and secondary (associated with stress, sepsis,

stroke, pulmonary and liver diseases, burn, trauma) Peptic Ulcer

Diseases (PUD)....................................................................................46

2. Medical treatment with anticholinergic agents in patients with

gastric and duodenal ulcers..............................................................47

3. Clinical Pharmacology of anticholinergic agents in patients with

peptic ulcer disease (measurements of anticholinergic agents in

the sera, urine in patients with duodenal ulcer).........................49

4. Comparative clinical pharmacology of anticholinergic drugs...51

5. Clinical evidence of the existence of gastrointestinal protection

differs from the decrease of gastric acid secretion

(Gastric cytoprotection) ....................................................................52

6. Randomized, multiclinical, prospective and multicentric study of

treatment of chronic gastric ulcer patients with vitamin A.......54

7. Comparative clinical pharmacology of “cytoprotective” and

“anti-secretory” drugs (multiclinical, randomized, prospective

and multicentric studies) in patients with chronic gastric and

duodenal ulcers...................................................................................57

8. General conclusion(s) of clinical pharmacological studies in

patients with peptic ulcer..................................................................60

Chapter 4 Clinical Pharmacology and Therapeutic Drug Monitoring of

Immunosuppressive Agents...................................................................64

1. Introduction..........................................................................................64

2. Mechanism of action and side effects.............................................65

3. General principles of Therapeutic Drug Monitoring (TDM).....75

4. Monitoring of individual immunosuppressive agents................82

5. Advances in immunosuppression – Future trends......................92

6. Conclusions..........................................................................................93

Chapter 5 1,3-β-Glucans: Drug Delivery and Pharmacology .........................106

1. Introduction........................................................................................106

3. Applications in drug delivery........................................................110

4. Applications in immunotherapy....................................................116

5. Conclusion .........................................................................................120

Acknowledgement ...........................................................................120

Chapter 6 Drug Interactions, Pharmacogenomics and Cardiovascular

Complication............................................................................................129

1. Introduction........................................................................................129

2. Hypertensive drugs..........................................................................132

3. Calcium Channel Blockers (CCBs)................................................137

4. Anticoagulants...................................................................................138

5. Statins..................................................................................................141

6. Antiarrhythmic..................................................................................144

7. Antiplatelet agents............................................................................144

8. Conclusion..........................................................................................146

Appendix............................................................................................148

Chapter 7 Current Status of Pharmacogenetics in Antithrombotic Drug

Therapy ...................................................................................................166

1. Introduction........................................................................................166

2. Antithrombotic therapy ..................................................................167

3. Pharmacogenomics ..........................................................................170

4. Warfarin pharmacogenetics ...........................................................173

5. Implementation of warfarin pharmacogenetics .........................178

6. Antiplatelet therapies ......................................................................180

7. Aspirin ...............................................................................................181

8. Clopidogrel high-risk pharmacokinetics .....................................183

9. Implementation of clopidogrel pharmacogenetics ....................187

10. New generation antithrombotic drugs ........................................188

11. Conclusions .......................................................................................189

Citation......................................................................................................207

Index...........................................................................................................209

About Author

David Renwick obtained his Ph.D. in Pharmaceutical Science from Public State University, Marlborough. He has served as a Guest Lecturer at several universities across Asia & Europe. His research interests in pharmaceutical sciences encompass pharmacotherapy, pharmacogenetics and pharmacokinetics. Renwick has authored and edited a number of articles, journal papers and major book chapters in the field of pharmaceutical sciences. He has also attended numerous scientific conferences and symposiums; and has presented 7 papers on pharmaceutical science.