Principles of Clinical Pharmacology

Arthur J. Atkinson, Jr., M.D., M.A.C.P., is Adjunct Professor of Pharmacology at the Feinberg Medical School of Northwestern University. He has held leadership roles in clinical pharmacology for more than 50 years, working in both academia and the pharmaceutical industry, and for NIH. He founded and for 24 years directed a Clinical Pharmacology Center at Northwestern, rising to the rank of Professor of Pharmacology and Medicine. He was subsequently Corporate Vice President for Clinical Development and Medical Affairs at the Upjohn Company. Following the Upjohn-Pharmacia merger, he was recruited to be Senior Advisor in Clinical Pharmacology at the NIH Clinical Center. There, he initiated a clinical pharmacology course and served as lead editor for the previous three editions of Principles of Clinical Pharmacology, the required text for the course. Dr. Atkinson has been elected Master of the American College of Physicians and to membership in the American Association of Physicians. He received the Harry Gold Award from ASPET, the Oscar Hunter Award from ASCPT, and the Award in Excellence from the PhRMA Foundation.

1. Introduction

PART 1: PHARMACOKINETICS 2. Clinical pharmacokinetics 3. Compartmental analysis of drug distribution 4. Drug absorption and bioavailability 5. Effects of renal disease on pharmacokinetics 6. Kinetics of hemodialysis and hemofiltration 7. Effects of liver disease on pharmacokinetics 8. Noncompartmental vs. compartmental approaches to pharmacokinetic analysis 9. Distributed models of drug kinetics 10. Population pharmacokinetics

PART 2: DRUG METABOLISM AND TRANSPORT 11. Pathways of drug metabolism 12. Biochemical mechanisms of drug toxicity 13. Chemical assay of drugs and drug metabolites 14. Equilibrative and concentrative transport 15. Pharmacogenetics 16. Drug interactions

PART 3: ASSESSMENT OF DRUG EFFECTS 17. Physiological and laboratory markers of drug effect 18. Dose response and concentration response analysis 19. Kinetics of pharmacologic effect 20. Disease progression models

PART 4: OPTIMIZING AND EVALUATING PATIENT THERAPY 21. Sex differences in pharmacokinetics and pharmacodynamics 22. Drug therapy in pregnant and nursing women 23. Drug therapy in neonates and pediatric patients 24. Drug therapy in the elderly 25. Clinical analysis of adverse drug reactions 26. Quality assessment of drug therapy

PART 5: DRUG DISCOVERY AND DEVELOPMENT 27. Project management 28. Drug discovery 29. Pre-clinical development 30. Animal scale up 31. Phase I studies 32. PK and PD considerations in the development of biotechnology products and large molecules 33. Design of clinical development programs 34. Good design practices for clinical trials 35. Role of the FDA in guiding drug development

Appendix I. Table of Laplace Transforms II. Answers to Study Problems