NEW INSIGHTS INTO TOXICITY AND DRUG TESTING Edited by Sivakumar Gowder New Insights into Toxicity and Drug Testing http://dx.doi.org/10.5772/55886 Edited by Sivakumar Gowder Contributors Ifeoma Obidike, Azad Mohammed, Michaela Reddy, Harvey Clewell, Thierry Lave, Melvin Andersen, Ray Greek, Abdelmigid, Nasir Mohamad, Peter Ward, David La, J Eric McDuffie, Sandra Snook, Elsa Dias, Carina Menezes, Elisabete Valério, Jose M Fuentes, Jacob John Van Tonder, Mary Gulumian, Vanessa Steenkamp Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2013 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work Any republication, referencing or personal use of the work must explicitly identify the original source Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher No responsibility is accepted for the accuracy of information contained in the published chapters The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book Publishing Process Manager Ana Pantar Technical Editor InTech DTP team Cover InTech Design team First published January, 2013 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com New Insights into Toxicity and Drug Testing, Edited by Sivakumar Gowder p cm ISBN 978-953-51-0946-4 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface VII Section Toxicity Chapter Pre-Clinical Assessment of the Potential Intrinsic Hepatotoxicity of Candidate Drugs Jacob John van Tonder, Vanessa Steenkamp and Mary Gulumian Chapter The Kidney Vero-E6 Cell Line: A Suitable Model to Study the Toxicity of Microcystins 29 Carina Menezes, Elisabete Valério and Elsa Dias Chapter Why are Early Life Stages of Aquatic Organisms more Sensitive to Toxicants than Adults? 49 Azad Mohammed Chapter Screening of Herbal Medicines for Potential Toxicities 63 Obidike Ifeoma and Salawu Oluwakanyinsola Chapter New Trends in Genotoxicity Testing of Herbal Medicinal Plants 89 Hala M Abdelmigid Section Drug Testing and Development 121 Chapter Animal Models in Drug Development 123 Ray Greek Chapter Renal Transporters and Biomarkers in Safety Assessment 153 P.D Ward, D La and J.E McDuffie VI Contents Chapter Autophagy: A Possible Defense Mechanism in Parkinson's Disease? 177 Rosa A González-Polo, Rubén Gómez-Sánchez, Lydia SánchezErviti, José M Bravo-San Pedro, Elisa Pizarro-Estrella, Mireia NisoSantano and José M Fuentes Chapter Physiologically Based Pharmacokinetic Modeling: A Tool for Understanding ADMET Properties and Extrapolating to Human 197 Micaela B Reddy, Harvey J Clewell III, Thierry Lave and Melvin E Andersen Chapter 10 Plasma Methadone Level Monitoring in Methadone Maintenance Therapy: A Personalised Methadone Therapy 219 Nasir Mohamad, Roslanuddin Mohd Salehuddin, Basyirah Ghazali, Nor Hidayah Abu Bakar, Nurfadhlina Musa, Muslih Abdulkarim Ibrahim, Liyana Hazwani Mohd Adnan, Ahmad Rashidi and Rusli Ismail Preface In this book, the section on Toxicity reveals the emerging technologies (profiling technolo‐ gies, 3D cultures etc.) to evaluate hepatotoxicity of candidate drugs; suitability of kidney Vero cell line in evaluating toxicity of microcystins; suitability of aquatic larva to evaluate environmental toxicants and advanced level techniques (next generation sequencing etc.) to screen the safety of medicinal plants Chapters in the section on Drug testing and Develop‐ ment reveal reductionist approach of using animal models in drug development, especially in toxicity testing; the role of renal transporters in the safety assessment of drugs; role of au‐ tophagy in Parkinson’s diseases and the clinical importance of Methadone Maintenance Therapy In this section, there are also interesting discussions on the emerging role of phys‐ iologically based pharmacokinetic modeling in the pharmaceutical industry throughout the drug development This book is a significant resource for scientists and physicians who are directly dealing with drugs / medicines and human life It is my privilege to present this book to the scientific community I extend my gratitude towards my mother, my late father and my brothers for introducing me to higher education My thanks to higher authorities, and colleagues of Qassim Univer‐ sity for their motivation to carry out this project I am continuously indebted to my wife Anitha for her encouragement and technical support for this book project I also acknowl‐ edge the interest and commitment from the Senior Commissioning Editor of InTech Ms Ana Pantar and the Publishing Process Manager Ms Sandra Bakic whose patience and focus were of immense support in this project Finally, I express deep and sincere gratitude to all the authors for their valuable contributions and scholarly cooperation for timely comple‐ tion of this book Dr Sivakumar Joghi Thatha Gowder Qassim University – College of Pharmacy Kingdom of Saudi Arabia Section Toxicity 230 New Insights into Toxicity and Drug Testing Variables Methadone