- Email: [email protected]
Chrono-drug-delivery focused on biological clock: intra- and inter-individual variability of molecular clock
Advanced Drug Delivery Reviews 62 (2010) 857–858
Contents lists available at ScienceDirect
Advanced Drug Delivery Reviews j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / a d d r
Preface
Chrono-drug-delivery focused on biological clock: intra- and inter-individual variability of molecular clock☆
This volume brings together the leading scientists in the fields of molecular chronobiology and chronopharmacology. Mammalians circadian pacemaker resides in SCN and influences a multitude of biological processes, including the sleep–wake rhythm. The circadian clock acts like a multifunction timer to regulate homeostatic systems such as sleep and activity, hormone levels, appetite, and other bodily functions with 24 h cycles. Biological rhythms not only impact the function of physiology, but the pathophysiology of diseases. Chronopharmacology is the investigative science that elucidates the biological rhythm dependencies of medications. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24 h rhythms of biochemical, physiological and behavioral processes under the control of circadian clock. Such chronopharmacological phenomena are influenced by not only the pharmacodynamics but also pharmacokinetics of medications. The knowledge of 24 h rhythm in the risk of disease plus evidence of 24 h rhythm dependencies of drug pharmacokinetics, effects, and safety constitutes the rationale for pharmacotherapy (chronotherapy). Chronotherapy is especially relevant in the following cases. The risk and/or intensity of the symptoms of disease vary predicably over time as exemplified by allergic rhinitis, arthritis, asthma, myocardial infarction, congestive heart failure, stroke, and peptic ulcer disease. Since many drugs vary in potency and/or toxicity associated with the rhythmicity of biochemical, physiological and behavioral processes, the intra-individual variability as well as inter-individual variability should be considered to aim at further improvement of rational pharmacotherapy. From viewpoints of pharmaceutics, the application of biological rhythm to pharmacotherapy may be accomplished by the appropriate timing of conventionally formulated tablets and capsules, and the special drug-delivery system to synchronize drug concentrations to rhythms in disease activity. New technology for delivering medications precisely in a time-modulated fashion by bedside or ambulatory pumps is developing to manage human diseases. Thus, the major goal of this theme issue — Chrono-drug-delivery focused on biological clock: Intra- and inter-individual variability of molecular clock, — is to bring together the two complementary fields of molecular chronobiology and drug-delivery system. Clock genes are identified as the genes that ultimately control a vast array of circadian rhythms in physiology and behavior. Clock gene
☆ This preface is part of the Advanced Drug Delivery Reviews theme issue on “Chronodrug-delivery focused on biological clock: Intra- and inter-individual variability of molecular clock”. 0169-409X/$ – see front matter © 2010 Published by Elsevier B.V. doi:10.1016/j.addr.2010.05.007
regulates several diseases such as cancer, metabolic syndrome and sleep etc. CLOCK mutation affects the expression of rhythmic genes in wild-type mice, but also affects that of non-rhythmic genes. On the other hand, the changes of the drug pharmacodynamic and pharmacokinetic parameters are influenced by not only interindividual variability but also intra-individual variability of medications. Identification of a rhythmic marker for selecting dosing time will lead to improved progress and diffusion of chronopharmacotherapy. The mechanisms underlying chronopharmacological findings should be clarified from the viewpoint of clock genes. On the other hand, several drugs have an effect on molecular clock. Thus, the knowledge of intra- and inter-individual variability of molecular clock should be applied for the clinical practice. The monitoring of rhythm, overcome of rhythm disruption and manipulation of rhythm from viewpoints of molecular clock are essential to improve progress and diffusion of chronopharmacotherapy. Such approach should be achieved by the new challenges in drug-delivery system that match the circadian rhythm. Recent strategy on pharmacotherapy has been focused on gene delivery and antibody delivery targeting specific molecular for some disease. Clock genes should be also one of the important candidates. I have invited the leading scientists of several fields of medicine and pharmacology to contribute in-depth reviews and annotated comments regarding drug-delivery opportunities of those medical conditions that are logical targets for the successful application of new drug-delivery systems and devices to improve outcomes by chronotherapeutic strategies. After an introduction to the field of molecular chronobiology, chronopharmacology, and candidate systems for chronotherapeutics by the guest editor, subsequent articles address the topics of 1) Chronotherapeutic strategy: rhythm monitoring, manipulation and disruption, 2) Mammalian circadian clock system: molecular mechanisms for pharmaceutical and medical sciences, 3) Chronopharmacological strategies: intraand inter-individual variability of molecular clock, 4) Chronopharmaceutical drug-delivery systems: hurdles, hype or hope? 5) Circadian rhythms in gene expression: relationships to physiology, disease, drug disposition and drug action, 6) The adjustment and manipulation of biological rhythms by light, nutrition, and abused drugs, 7) Disruption of the circadian system by environmental factors: effects of hypoxia, magnetic fields and general anesthetic agents, 8) Asthma: chronopharmacotherapy and the molecular clock, 9) Cardiovascular disease: chronopharmacotherapy and the molecular clock, 10) Chronobiological aspects of nutrition, metabolic syndrome and obesity, and 11) Chronotherapy and the
858
Preface
molecular clock: clinical implications in oncology. The content of these articles clearly makes apparent many potential new applications of existing drug-delivery systems and devices, and it serves also as the basis for future developments. The aim of those reviews are to provide an overview of the regulatory system of biological rhythm from viewpoints of clock genes and the possibility of pharmacotherapy based on the intra- and inter-individual variability of clock genes.
Shigehiro Ohdo (Theme Editor) Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan E-mail address: [email protected]
Contents lists available at ScienceDirect
Advanced Drug Delivery Reviews j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / a d d r
Preface
Chrono-drug-delivery focused on biological clock: intra- and inter-individual variability of molecular clock☆
This volume brings together the leading scientists in the fields of molecular chronobiology and chronopharmacology. Mammalians circadian pacemaker resides in SCN and influences a multitude of biological processes, including the sleep–wake rhythm. The circadian clock acts like a multifunction timer to regulate homeostatic systems such as sleep and activity, hormone levels, appetite, and other bodily functions with 24 h cycles. Biological rhythms not only impact the function of physiology, but the pathophysiology of diseases. Chronopharmacology is the investigative science that elucidates the biological rhythm dependencies of medications. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24 h rhythms of biochemical, physiological and behavioral processes under the control of circadian clock. Such chronopharmacological phenomena are influenced by not only the pharmacodynamics but also pharmacokinetics of medications. The knowledge of 24 h rhythm in the risk of disease plus evidence of 24 h rhythm dependencies of drug pharmacokinetics, effects, and safety constitutes the rationale for pharmacotherapy (chronotherapy). Chronotherapy is especially relevant in the following cases. The risk and/or intensity of the symptoms of disease vary predicably over time as exemplified by allergic rhinitis, arthritis, asthma, myocardial infarction, congestive heart failure, stroke, and peptic ulcer disease. Since many drugs vary in potency and/or toxicity associated with the rhythmicity of biochemical, physiological and behavioral processes, the intra-individual variability as well as inter-individual variability should be considered to aim at further improvement of rational pharmacotherapy. From viewpoints of pharmaceutics, the application of biological rhythm to pharmacotherapy may be accomplished by the appropriate timing of conventionally formulated tablets and capsules, and the special drug-delivery system to synchronize drug concentrations to rhythms in disease activity. New technology for delivering medications precisely in a time-modulated fashion by bedside or ambulatory pumps is developing to manage human diseases. Thus, the major goal of this theme issue — Chrono-drug-delivery focused on biological clock: Intra- and inter-individual variability of molecular clock, — is to bring together the two complementary fields of molecular chronobiology and drug-delivery system. Clock genes are identified as the genes that ultimately control a vast array of circadian rhythms in physiology and behavior. Clock gene
☆ This preface is part of the Advanced Drug Delivery Reviews theme issue on “Chronodrug-delivery focused on biological clock: Intra- and inter-individual variability of molecular clock”. 0169-409X/$ – see front matter © 2010 Published by Elsevier B.V. doi:10.1016/j.addr.2010.05.007
regulates several diseases such as cancer, metabolic syndrome and sleep etc. CLOCK mutation affects the expression of rhythmic genes in wild-type mice, but also affects that of non-rhythmic genes. On the other hand, the changes of the drug pharmacodynamic and pharmacokinetic parameters are influenced by not only interindividual variability but also intra-individual variability of medications. Identification of a rhythmic marker for selecting dosing time will lead to improved progress and diffusion of chronopharmacotherapy. The mechanisms underlying chronopharmacological findings should be clarified from the viewpoint of clock genes. On the other hand, several drugs have an effect on molecular clock. Thus, the knowledge of intra- and inter-individual variability of molecular clock should be applied for the clinical practice. The monitoring of rhythm, overcome of rhythm disruption and manipulation of rhythm from viewpoints of molecular clock are essential to improve progress and diffusion of chronopharmacotherapy. Such approach should be achieved by the new challenges in drug-delivery system that match the circadian rhythm. Recent strategy on pharmacotherapy has been focused on gene delivery and antibody delivery targeting specific molecular for some disease. Clock genes should be also one of the important candidates. I have invited the leading scientists of several fields of medicine and pharmacology to contribute in-depth reviews and annotated comments regarding drug-delivery opportunities of those medical conditions that are logical targets for the successful application of new drug-delivery systems and devices to improve outcomes by chronotherapeutic strategies. After an introduction to the field of molecular chronobiology, chronopharmacology, and candidate systems for chronotherapeutics by the guest editor, subsequent articles address the topics of 1) Chronotherapeutic strategy: rhythm monitoring, manipulation and disruption, 2) Mammalian circadian clock system: molecular mechanisms for pharmaceutical and medical sciences, 3) Chronopharmacological strategies: intraand inter-individual variability of molecular clock, 4) Chronopharmaceutical drug-delivery systems: hurdles, hype or hope? 5) Circadian rhythms in gene expression: relationships to physiology, disease, drug disposition and drug action, 6) The adjustment and manipulation of biological rhythms by light, nutrition, and abused drugs, 7) Disruption of the circadian system by environmental factors: effects of hypoxia, magnetic fields and general anesthetic agents, 8) Asthma: chronopharmacotherapy and the molecular clock, 9) Cardiovascular disease: chronopharmacotherapy and the molecular clock, 10) Chronobiological aspects of nutrition, metabolic syndrome and obesity, and 11) Chronotherapy and the
858
Preface
molecular clock: clinical implications in oncology. The content of these articles clearly makes apparent many potential new applications of existing drug-delivery systems and devices, and it serves also as the basis for future developments. The aim of those reviews are to provide an overview of the regulatory system of biological rhythm from viewpoints of clock genes and the possibility of pharmacotherapy based on the intra- and inter-individual variability of clock genes.
Shigehiro Ohdo (Theme Editor) Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan E-mail address: [email protected]