Cytochrome P450 (CYP) is a super family of phase I enzyme in the biotransformation of xenobiotics and medications. Most medications undergo deactivation by CYP, and then are eliminated through either bile or kidneys from the body. CYP isozymes play a crucial role in drug interactions that may result in enhanced toxicity, reduced efficacy or onset of adverse reactions. On the other hand, many agents affecting CYP expression and activity may alter metabolic rate of different medications co-administrated. Therefore, the molecular basis, regulation by inducers or inhibitors, and pharmacologic reaction of specific CYP isozymes are the key issues of biochemical mechanisms, pharmaceutical development and safe use of various medications. This book is to meet the needs from basic molecular biochemists, pharmacologists, pharmacists, medical students, clinical practitioners and scientists, as well as broad readers who wish to understand how an herbal extract, medication or natural supplement is metabolized or transformed in the liver or other sites for deactivation and elimination. Special focuses are paid to herbal extracts and medications in the treatment of neuro-psychiatric or cardiovascular disorders, diabetes and viral hepatitis. Detailed dissection of drug interactions in a particular field intends to provide rationales for useful guidance of safe drug use in daily practice. The contributing authors are basic scientists, pharmacists, pharmacologists and on-service physicians in cardiovascular, neuro-psychiatric, gastroenterologic and hepatologic fields from Europe (Germany, France, Portugal), Australia, the US and China. Thus, the book is the collection of master pieces by well-known experts from various regions of the world, and represents the current understanding of CYP enzyme reaction and a contemporary coverage of possible drug interactions in involved fields. The featured chapters are scientific elucidation of basic biochemistry, pharmacology and clinical investigations in the interest of drug metabolism, interaction and safe use guidance in the single focus of this microsomal enzyme with multi-facet metabolic function. Jian Wu, M.D., Ph.D. Fudan University Shanghai Medical College, Shanghai, China

Preface ix

Chapter 1 Cytochrome P450: Electron Transfer and Sensors 1

Frieder W. Scheller, Aysu Yarmana, and Ulla Wollenberger

Chapter 2 Cytochrome P450-Mediated Toxicity of Therapeutic Drugs 13

Mariana Matias, Catarina Canario, Samuel Silvestre, Amilcar Falcao and Gilberto Alves

Chapter 3 Evaluation of Cytochrome P450 Enzymes in Drag Interactions 51

Xin Wang

Chapter 4 Cytochrome P450 Enzymes in Atherosclerosis 87

Iryna Voloshyna and Allison B. Reiss

Chapter 5 Drug Resistance of Nucleos(t)ide Analogues and Related Adverse Events in Chronic Hepatitis B 107

Li Zong

Chapter 6 Metabolism, Interaction and Use Guidelines of Anti-HBV and Anti-HCV Medications 121

Jinsheng Guo and Jian Wu

Chapter 7 Role of Cytochrome P450 Enzymes in Psychotropic Drag Metabolism and Clinical Implications 141

Irina Piatkov and Trudi Jones

Index 181

中国医科院医学信息研究所