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Chronobiology, drug-delivery, and chronotherapeutics
Available online at www.sciencedirect.com
Advanced Drug Delivery Reviews 59 (2007) 823 – 824 www.elsevier.com/locate/addr
Preface
Chronobiology, drug-delivery, and chronotherapeutics ☆
This volume brings together the leading scientists in the fields of medical chronobiology and chronopharmacology. Chronobiology is the study of biological rhythms and the mechanisms that drive them. Chronopharmacology is the study of the manner in which the endogenous body rhythms of diverse period – from the short-period pulsatile, to the intermediate-period circadian (24-hour), and to the longerperiod menstrual and annual ones – affect the pharmacokinetics and dynamics of medications as a function of the time when they are ingested, injected, infused, or applied by other routes. Finally, chronotherapeutics is the delivery of medications in the right concentration to the right targeted tissues at the right time to meet biological rhythm-determined needs, e.g., rhythms in the mechanisms of disease, symptom intensity, and/ or patient tolerance, to optimize desired and minimize and avert adverse effects. For nearly three decades, medical chronobiologists have been regularly meeting with peers at international congresses of chronobiology and chronopharmacology to report important findings relating to predictable-intime 24-hour variation in the pathophysiology and symptom intensity of acute and chronic human diseases and to dosingtime differences in the kinetics and dynamics of medications. For decades drug-delivery and pharmaceutical scientists have been meeting with peers at national and international drugdelivery and pharmaceutical science congresses to present new advances in drug-delivery technology, systems, and devices. Medical chronobiologists have been searching for systems to make possible better and safer therapeutics based on the principles and findings of chronobiology, and drug-delivery scientists have been searching for new applications of already existing as well as new systems and technology to make possible better and safer therapeutics. Over the years, the crosstalk between the scientists of these two fields has been limited to but one New York Academy of Sciences congress held in 1991, more than 15 years ago. Since then, there have been tremendous advances in the knowledge of medical chronobiology and in drug-delivery systems and technology. Thus,
☆
This preface is part of Advanced Drug Delivery Reviews theme issue on “Chronobiology, Drug Delivery, and Chronotherapeutics". 0169-409X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.addr.2007.08.004
the major goal of this theme issue – Chronobiology, drug delivery, and chronotherapeutics – is to bring together the two complementary fields of medical chronobiology and drugdelivery engineering. Many chronic and acute medical conditions exhibit prominent circadian patterns of symptom manifestation and severity. Among the many examples are allergic rhinitis, bronchial asthma, and peptic ulcer disease; all tend to worsen overnight. The symptoms of rheumatoid arthritis are worse in the morning, while those of osteoarthritis are worse at night. The risk of many cardiovascular events, like angina pectoris, myocardial infarction, and thrombotic and hemorrhagic stroke, is greatest in the morning. Abnormally high blood pressure, i.e., hypertension, which is not a disease but a major risk factor for cardiac and vascular disease, displays different circadian patterns in different patient groups. The pattern seen in normotension and simple, uncomplicated essential hypertension is one of elevated pressure during daytime activity and reduced pressure, by 10 to 20%, during nighttime sleep. However, the pattern is different in secondary hypertension (high blood pressure occurring secondary to another coexisting medical condition, e.g., diabetes and renal diseases); the 24-hour pattern in this situation is characterized by a blunted decline or even a rise in blood pressure to a higher level during nighttime sleep than found during daytime activity. Thus, the treatment of hypertension not only includes the usual clinical goal of reducing mean blood pressure level, but also the normalization of the entire blood pressure circadian pattern. The predictable day–night variation in the symptoms of chronic medical conditions, risk of severe life-threatening cardiovascular events, and in medical conditions that are predisposing to serious disease presents the opportunity for a new, i.e., chronotherapeutic, treatment strategy that involves the delivery of medications so they are synchronized in time to biological need that varies according to the chronobiology of the targeted tissues. Thus, future applications of drug-delivery systems ought to be based on release-response to high and low concentrations of analytes/markers of disease activity as an innovative means of realizing optimal chronotherapeutic systems. We 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
824
Preface 59 (2007) 823–824
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 general and medial chronobiology, chronopharmacolgy, and candidate systems for chronotherapeutics by the guest editors, subsequent articles address the topics of: (i) allergy and asthma, (ii) pain and arthritis, (iii) aminogylcoside antibiotics, (iv) blood pressure rhythms, (v) hypertension, (vi) cardiac arrhythmias, (vii) ischemic heart disease, (viii) hemostasis, (ix) endocrine system, (x) clocks for rhythmic delivery of cancer medications, (xi) cell cycle automaton model for cancer chronotherapy, and (xii) modeling oxaliplatin drug-delivery to circadian rhythms in drug metabolism and host tolerance. 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.
Michael H. Smolensky (Theme Editor) Division of Environmental and Occupational Health Sciences, School of Public Health, The University of Texas Health Science Center at Houston, USA E-mail address: [email protected]. Nicholas A. Peppas (Theme Editor) Departments of Chemical Engineering, Biomedical Engineering, and College of Pharmacy The University of Texas at Austin, USA E-mail address: [email protected].
Advanced Drug Delivery Reviews 59 (2007) 823 – 824 www.elsevier.com/locate/addr
Preface
Chronobiology, drug-delivery, and chronotherapeutics ☆
This volume brings together the leading scientists in the fields of medical chronobiology and chronopharmacology. Chronobiology is the study of biological rhythms and the mechanisms that drive them. Chronopharmacology is the study of the manner in which the endogenous body rhythms of diverse period – from the short-period pulsatile, to the intermediate-period circadian (24-hour), and to the longerperiod menstrual and annual ones – affect the pharmacokinetics and dynamics of medications as a function of the time when they are ingested, injected, infused, or applied by other routes. Finally, chronotherapeutics is the delivery of medications in the right concentration to the right targeted tissues at the right time to meet biological rhythm-determined needs, e.g., rhythms in the mechanisms of disease, symptom intensity, and/ or patient tolerance, to optimize desired and minimize and avert adverse effects. For nearly three decades, medical chronobiologists have been regularly meeting with peers at international congresses of chronobiology and chronopharmacology to report important findings relating to predictable-intime 24-hour variation in the pathophysiology and symptom intensity of acute and chronic human diseases and to dosingtime differences in the kinetics and dynamics of medications. For decades drug-delivery and pharmaceutical scientists have been meeting with peers at national and international drugdelivery and pharmaceutical science congresses to present new advances in drug-delivery technology, systems, and devices. Medical chronobiologists have been searching for systems to make possible better and safer therapeutics based on the principles and findings of chronobiology, and drug-delivery scientists have been searching for new applications of already existing as well as new systems and technology to make possible better and safer therapeutics. Over the years, the crosstalk between the scientists of these two fields has been limited to but one New York Academy of Sciences congress held in 1991, more than 15 years ago. Since then, there have been tremendous advances in the knowledge of medical chronobiology and in drug-delivery systems and technology. Thus,
☆
This preface is part of Advanced Drug Delivery Reviews theme issue on “Chronobiology, Drug Delivery, and Chronotherapeutics". 0169-409X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.addr.2007.08.004
the major goal of this theme issue – Chronobiology, drug delivery, and chronotherapeutics – is to bring together the two complementary fields of medical chronobiology and drugdelivery engineering. Many chronic and acute medical conditions exhibit prominent circadian patterns of symptom manifestation and severity. Among the many examples are allergic rhinitis, bronchial asthma, and peptic ulcer disease; all tend to worsen overnight. The symptoms of rheumatoid arthritis are worse in the morning, while those of osteoarthritis are worse at night. The risk of many cardiovascular events, like angina pectoris, myocardial infarction, and thrombotic and hemorrhagic stroke, is greatest in the morning. Abnormally high blood pressure, i.e., hypertension, which is not a disease but a major risk factor for cardiac and vascular disease, displays different circadian patterns in different patient groups. The pattern seen in normotension and simple, uncomplicated essential hypertension is one of elevated pressure during daytime activity and reduced pressure, by 10 to 20%, during nighttime sleep. However, the pattern is different in secondary hypertension (high blood pressure occurring secondary to another coexisting medical condition, e.g., diabetes and renal diseases); the 24-hour pattern in this situation is characterized by a blunted decline or even a rise in blood pressure to a higher level during nighttime sleep than found during daytime activity. Thus, the treatment of hypertension not only includes the usual clinical goal of reducing mean blood pressure level, but also the normalization of the entire blood pressure circadian pattern. The predictable day–night variation in the symptoms of chronic medical conditions, risk of severe life-threatening cardiovascular events, and in medical conditions that are predisposing to serious disease presents the opportunity for a new, i.e., chronotherapeutic, treatment strategy that involves the delivery of medications so they are synchronized in time to biological need that varies according to the chronobiology of the targeted tissues. Thus, future applications of drug-delivery systems ought to be based on release-response to high and low concentrations of analytes/markers of disease activity as an innovative means of realizing optimal chronotherapeutic systems. We 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
824
Preface 59 (2007) 823–824
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 general and medial chronobiology, chronopharmacolgy, and candidate systems for chronotherapeutics by the guest editors, subsequent articles address the topics of: (i) allergy and asthma, (ii) pain and arthritis, (iii) aminogylcoside antibiotics, (iv) blood pressure rhythms, (v) hypertension, (vi) cardiac arrhythmias, (vii) ischemic heart disease, (viii) hemostasis, (ix) endocrine system, (x) clocks for rhythmic delivery of cancer medications, (xi) cell cycle automaton model for cancer chronotherapy, and (xii) modeling oxaliplatin drug-delivery to circadian rhythms in drug metabolism and host tolerance. 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.
Michael H. Smolensky (Theme Editor) Division of Environmental and Occupational Health Sciences, School of Public Health, The University of Texas Health Science Center at Houston, USA E-mail address: [email protected]. Nicholas A. Peppas (Theme Editor) Departments of Chemical Engineering, Biomedical Engineering, and College of Pharmacy The University of Texas at Austin, USA E-mail address: [email protected].