APPLICATIONS OF MICRODIALYSIS IN PHARMACEUTICAL SCIENCE ffirs01.indd iffirs01.indd i 6/29/2011 3:11:19 PM6/29/2011 3:11:19 PM APPLICATIONS OF MICRODIALYSIS IN PHARMACEUTICAL SCIENCE Edited by TUNG-HU TSAI National Yang-Ming University Taipei, Taiwan A JOHN WILEY & SONS, INC., PUBLICATION ffirs02.indd iiiffirs02.indd iii 6/29/2011 3:11:20 PM6/29/2011 3:11:20 PM Copyright © 2011 by John Wiley & Sons, Inc. All rights reserved. Published by John Wiley & Sons, Inc., Hoboken, New Jersey. Published simultaneously in Canada. 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For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com. Library of Congress Cataloging-in-Publication Data: Applications of microdialysis in pharmaceutical science / [edited by] Tung-Hu Tsai. p. ; cm. Includes bibliographical references and index. ISBN 978-0-470-40928-2 (cloth : alk. paper) 1. Pharmaceutical chemistry. 2. Drug development. 3. Brain macrodialysis. I. Tsai, Tung-Hu. [DNLM: 1. Chemistry, Pharmaceutical–methods. 2. Microdialysis–methods. QV 744] RM301.25.A67 2011 615'.19–dc22 2011010963 Printed in Singapore oBook ISBN: 9781118011294 ePDF ISBN: 9781118011270 ePub ISBN: 9781118011287 10 9 8 7 6 5 4 3 2 1 ffirs03.indd ivffirs03.indd iv 6/29/2011 3:11:20 PM6/29/2011 3:11:20 PM CONTENTS CONTRIBUTORS xi 1 Introduction to Applications of Microdialysis in Pharmaceutical Science 1 Tung-Hu Tsai 2 Microdialysis in Drug Discovery 7 Christian Höcht 1. Introduction, 7 2. Phases of Drug Development, 8 3. Role of Biomarkers in Drug Development, 11 4. Role of Pharmacokinetic–Pharmacodynamic Modeling in Drug Development, 12 5. Role of Microdialysis in Drug Development, 15 6. Microdialysis Sampling in the Drug Development of Specifi c Therapeutic Groups, 20 7. Regulatory Aspects of Microdialysis Sampling in Drug Development, 29 8. Conclusions, 30 3 Analytical Considerations for Microdialysis Sampling 39 Pradyot Nandi, Courtney D. Kuhnline, and Susan M. Lunte 1. Introduction, 39 2. Analytical Methodologies, 49 3. Conclusions, 75 v ftoc.indd vftoc.indd v 6/29/2011 3:11:22 PM6/29/2011 3:11:22 PM vi CONTENTS 4 Monitoring Dopamine in the Mesocorticolimbic and Nigrostriatal Systems by Microdialysis: Relevance for Mood Disorders and Parkinson’s Disease 93 Giuseppe Di Giovanni, Massimo Pierucci, and Vincenzo Di Matteo 1. Introduction, 93 2. Pathophysiology of Serotonin–Dopamine Interaction: Implication for Mood Disorders, 94 3. Dopamine Depletion in the Nigrostriatal System: Parkinson’s Disease, 109 4. Conclusions, 120 5 Monitoring Neurotransmitter Amino Acids by Microdialysis: Pharmacodynamic Applications 151 Sandrine Parrot, Bernard Renaud, Luc Zimmer, and Luc Denoroy 1. Introduction, 151 2. Monitoring Neurotransmitter Amino Acids by Microdialysis, 152 3. Basic Research on Receptors, 162 4. Psychostimulants and Addictive Drugs, 168 5. Analgesia, 177 6. Ischemia–Anoxia, 182 7. Conclusions and Perspectives, 188 6 Microdialysis as a Tool to Unravel Neurobiological Mechanisms of Seizures and Antiepileptic Drug Action 207 Ilse Smolders, Ralph Clinckers, and Yvette Michotte 1. Introduction, 207 2. Microdialysis to Characterize Seizure-Related Neurobiological and Metabolic Changes in Animal Models and in Humans, 209 3. Microdialysis as a Chemoconvulsant Delivery Tool in Animal Seizure Models, 217 4. Microdialysis Used to Elucidate Mechanisms of Electrical Brain Stimulation and Neuronal Circuits Involved in Seizures, 218 5. Microdialysis Used to Unravel the Mechanisms of Action of Established Antiepileptic Drugs and New Therapeutic Strategies, 219 6. Microdialysis Studies in the Search for Mechanisms of Adverse Effects of Clinically Used Drugs, Drugs of Abuse, and Toxins, 224 7. Combining Microdialysis with Other Complementary Neurotechniques to Unravel Mechanisms of Seizures and Epilepsy, 226 ftoc.indd viftoc.indd vi 7/7/2011 5:25:20 PM7/7/2011 5:25:20 PM CONTENTS vii 8. The Advantage of Microdialysis Used to Sample Biophase Antiepileptic Drug Levels and to Monitor Neurotransmitters as Markers for Anticonvulsant Activity, 228 9. Microdialysis Used to Study Relationships Between Epilepsy and Its Comorbidities, 236 7 Microdialysis in Lung Tissue: Monitoring of Exogenous and Endogenous Compounds 255 Thomas Feurstein and Markus Zeitlinger 1. Introduction, 255 2. Special Aspects Associated with Lung Microdialysis Compared to Microdialysis in Other Tissues, 255 3. Insertion of Microdialysis Probes into Lung Tissue, 256 4. Insertion of Microdialysis Probes into the Bronchial System, 257 5. Types of Probes, 258 6. Endogenous Compounds, 258 7. Exogenous Drugs, 259 8. Animal Data, 260 9. Clinical Data, 262 10. Comparison of Pharmacokinetic Data in Lung Obtained by Microdialysis and Other Techniques, 264 11. Predictability of Lung Concentrations by Measurements in Other Tissues, 265 8 Microdialysis in the Hepatobiliary System: Monitoring Drug Metabolism, Hepatobiliary Excretion, and Enterohepatic Circulation 275 Yu-Tse Wu and Tung-Hu Tsai 1. Introduction, 275 2. Experimental Considerations of Pharmacokinetic Studies, 279 3. Pharmacokinetic and Hepatobiliary Excretion Studies Employing Microdialysis, 284 4. Conclusions, 287 9 Microdialysis Used to Measure the Metabolism of Glucose, Lactate, and Glycerol 295 Greg Nowak 1. Introduction, 295 2. Glucose, 299 3. Lactate, 301 4. Lactate/Pyruvate Ratio, 303 5. Glycerol, 303 ftoc.indd viiftoc.indd vii 6/29/2011 3:11:22 PM6/29/2011 3:11:22 PM viii CONTENTS 10 Clinical Microdialysis in Skin and Soft Tissues 313 Martina Sahre, Runa Naik, and Hartmut Derendorf 1. Introduction, 313 2. Tissue Bioavailability, 314 3. PK–PD Indices, 323 4. Topical Bioequivalence, 329 5. Endogenous Compounds, 330 6. Conclusions, 331 11 Microdialysis on Adipose Tissue: Monitoring Tissue Metabolism and Blood Flow in Humans 335 Gijs H. Goossens, Wim H. M. Saris, and Ellen E. Blaak 1. Introduction, 335 2. Principles and Practical Considerations in the Use of Microdialysis on Adipose Tissue, 336 3. Use of Microdialysis on Adipose Tissue in Humans, 342 4. Summary and Conclusions, 353 12 Microdialysis as a Monitoring System for Human Diabetes 359 Anna Ciechanowska, Jan M. Wojcicki, Iwona Maruniak-Chudek, Piotr Ladyzynski, and Janusz Krzymien 1. Introduction, 359 2. Monitoring Acute Complications of Diabetes, 362 13 Microdialysis Use in Tumors: Drug Disposition and Tumor Response 403 Qingyu Zhou and James M. Gallo 1. Introduction, 403 2. Microdialysis as a Sampling Technique in Oncology, 404 3. Experimental Considerations, 408 4. Examples of the Use of Microdialysis to Characterize Drug Disposition in Tumor, 414 5. Use of Microdialysis in the Evaluation of Tumor Response to Therapy, 423 6. Conclusions and Future Perspectives, 423 14 Microdialysis Versus Imaging Techniques for In Vivo Drug Distribution Measurements 431 Martin Brunner 1. Introduction, 431 2. Microdialysis, 432 3. Imaging Techniques, 434 4. Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy, 434 ftoc.indd viiiftoc.indd viii 6/29/2011 3:11:22 PM6/29/2011 3:11:22 PM CONTENTS ix 5. Positron–Emission Tomography, 435 6. Combination of Microdialysis and Imaging Techniques, 436 7. Summary and Conclusions, 438 15 In Vitro Applications of Microdialysis 445 Wen-Chuan Lee and Tung-Hu Tsai 1. Introduction, 445 2. Microdialysis Used in Culture Systems, 446 3. Microdialysis Used in Enzyme Kinetics, 453 4. Microdialysis Used in Protein Binding, 455 5. Conclusions, 456 16 Microdialysis in Drug–Drug Interaction 465 Mitsuhiro Wada, Rie Ikeda, and Kenichiro Nakashima 1. Introduction, 465 2. Pharmacokinetic Drug–Drug Interaction, 472 3. Pharmacodynamic Drug–Drug Interaction, 487 4. Conclusions, 501 17 Microdialysis in Environmental Monitoring 509 Manuel Miró and Wolfgang Frenzel 1. Introduction, 509 2. In Vivo and In Situ Sampling: Similarities and Differences, 510 3. Critical Parameters Infl uencing Relative Recoveries, 513 4. Detection Techniques, 518 5. Calibration Methods, 519 6. Environmental Applications of Microdialysis, 520 7. Conclusions and Future Trends, 524 INDEX 531 ftoc.indd ixftoc.indd ix 6/29/2011 8:14:06 PM6/29/2011 8:14:06 PM CONTRIBUTORS Ellen E. Blaak, Maastricht University Medical Centre, Maastricht, The Netherlands Martin Brunner, Medical University of Vienna, Vienna, Austria Anna Ciechanowska, Polish Academy of Sciences, Warsaw, Poland Ralph Clinckers, Vrije Universiteit Brussels, Brussels, Belgium Luc Denoroy, Universit é de Lyon and Lyon Neuroscience Research Center, BioRaN Team, Lyon, France; Universit é Lyon 1, Villeurbanne, France Hartmut Derendorf, University of Florida, Gainesville, Florida Giuseppe Di Giovanni, University of Malta, Msida, Malta; Cardiff University, Cardiff, UK Vincenzo Di Matteo, Istituto di Richerche Farmacologiche Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy Thomas Feurstein, Medical University of Vienna, Vienna, Austria Wolfgang Frenzel, Technical University of Berlin, Berlin, Germany James M. Gallo, Mount Sinai School of Medicine, New York, New York Gijs H. Goossens, Maastricht University Medical Centre, Maastricht, The Netherlands Christian H ö cht, Universidad de Buenos Aires, Buenos Aires, Argentina Rie Ikeda, Nagasaki University, Nagasaki, Japan Janusz Krzymien, Medical University of Warsaw, Warsaw, Poland xi flast.indd xiflast.indd xi 6/29/2011 8:14:06 PM6/29/2011 8:14:06 PM xii CONTRIBUTORS Courtney D. Kuhnline, University of Kansas, Lawrence, Kansas Piotr Ladyzynski, Polish Academy of Sciences, Warsaw, Poland Wen - Chuan Lee, National Yang - Ming University, Taipei, Taiwan Susan M. Lunte, University of Kansas, Lawrence, Kansas Iwona Maruniak - Chudek, Medical University of Silesia, Katowice, Poland Yvette Michotte, Vrije Universiteit Brussels, Brussels, Belgium Manuel Mir ó , University of the Balearic Islands, Palma de Mallorca, Illes Balears, Spain Runa Naik, University of Florida, Gainesville, Florida Kenichiro Nakashima, Nagasaki University, Nagasaki, Japan Pradyot Nandi, University of Kansas, Lawrence, Kansas Greg Nowak, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden Sandrine Parrot, Universit é de Lyon and Lyon Neuroscience Research Center, NeuroChem, Lyon, France; Universit é Lyon 1, Villeurbanne, France Massimo Pierucci, University of Malta, Msida, Malta Bernard Renaud, Universit é de Lyon and Lyon Neuroscience Research Center, NeuroChem, Lyon, France; Universit é Lyon 1, Villeurbanne, France Martina Sahre, University of Florida, Gainesville, Florida Wim H. M. Saris, Maastricht University Medical Centre, Maastricht, The Netherlands Ilse Smolders, Vrije Universiteit Brussels, Brussels, Belgium Tung - Hu Tsai, National Yang - Ming University and Taipei City Hospital, Taipei, Taiwan Mitsuhiro Wada, Nagasaki University, Nagasaki, Japan Jan M. Wojcicki, Polish Academy of Sciences, Warsaw, Poland Yu - Tse Wu, National Yang - Ming University, Taipei, Taiwan Markus Zeitlinger, Medical University of Vienna, Vienna, Austria Qingyu Zhou, Mount Sinai School of Medicine, New York, New York Luc Zimmer, Universit é de Lyon and Lyon Neuroscience Research Center, BioRaN Team, Lyon, France; Universit é Lyon 1, Villeurbanne, France flast.indd xiiflast.indd xii 7/7/2011 5:25:19 PM7/7/2011 5:25:19 PM [...]... estimation of accurate PK–PD models of new chemical entities is possible by means of microdialysis PET Microdialysis is also well suited for the determination of drug protein binding during early drug development The microdialysis technique allows the determination of in vivo protein binding using microdialysis sampling in blood and simultaneous blood sampling [33,34] The in vivo determination of protein binding... binding using the microdialysis method permits a more accurate determination of protein binding with regard to in vitro protocols, because it was found that in vitro determination systematically underestimated the unbound fraction [35] In addition, microdialysis permits the determination of the temporal course of protein binding in the same animal to determine saturation of the plasma protein binding... agonist of the c02.indd 23 7/11/2011 12:15:03 PM 24 MICRODIALYSIS IN DRUG DISCOVERY nicotinic acetylcholine receptor α4β2 subtype, in vivo microdialysis in freely moving rats showed that oral administration of varenicline caused moderate increases in dopamine release in the nucleus accumbens, inducing maximal response after 2 h of varenicline dosing [58] In addition, it was found that maximal dopamine... process In addition, as regards the role of PK–PD modeling during all stages of drug development and the ability of microdialysis for continuous monitoring of tissue extracellular levels of drugs and their effect on biochemical markers, this technique allows an early proof of concept of the activity of new chemical entities in the first stages of drug development, especially in preclinical models of efficacy... application of microdialysis in drug development (Table 5) As most cen- c02.indd 20 7/11/2011 12:15:03 PM 21 MICRODIALYSIS SAMPLING TABLE 5 Role of Microdialysis in Drug Development of Centrally Acting Drugs Therapeutic Group Utility of Microdialysis Sampling Antiepileptic drugs Estimation of hippocampal bioavailability Assessment of compromise of efflux transporters in brain distribution Assessment of neurochemical... essential in the preclinical phase of drug development, because these in vitro systems can speed up the processes of screening lead compounds, assessing metabolic stability, and evaluating permeation across membranes such as the gastrointestinal tract and the blood–brain barrier Microdialysis sampling of cell culture systems, enzyme kinetics, and proteinbinding assays are discussed in Chapter 15 Drug interaction... topic for clinical pharmacy, especially since the incidence of drug interactions is expected to increase with the increasing number of new drugs brought to the market Exploring the relevance and mechanisms of drug interactions will assist clinicians in avoiding these often serious events Herbal products, dietary supplements, and foods can also induce drug interactions The reduced concentration of a free-form... PK–PD relationships of lead compounds in animal models of efficacy, this technique allows an early determination of the proof of concept of new chemical entities during preclinical drug development and selection of the most adequate dosing interval for phase I clinical trials Although microdialysis could also contribute in early phases of clinical drug development, its applicability in human studies could... aspect of microdialysis technique is highly interesting for evaluation of the brain/plasma ratio in animal models of efficacy Moreover, regional distribution in brain parenchyma of central-acting drugs could be assessed by means of implantation of several probes in different central nuclei It is important to mention that imaging techniques also permit assessment of the time profile of tissue pharmacokinetics... 1 Aspects of Various Phases of Drug Development and the Utility of Microdialysis Sampling 467 335 Costs ($ millions) N.A N.A ++ +++++ N.A Applicability of Microdialysisa 10 MICRODIALYSIS IN DRUG DISCOVERY Another important objective of preclinical drug development is the establishment of the dosing interval of lead compounds to be used in early clinical trials At this point, development of mechanism-based . APPLICATIONS OF MICRODIALYSIS IN PHARMACEUTICAL SCIENCE ffirs01.indd iffirs01.indd i 6/29/2011 3:11:19 PM6/29/2011 3:11:19 PM APPLICATIONS OF MICRODIALYSIS. 1. Introduction, 445 2. Microdialysis Used in Culture Systems, 446 3. Microdialysis Used in Enzyme Kinetics, 453 4. Microdialysis Used in Protein Binding,