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The human biorhythm is closely related to the blood pressure level and the effect of the antihypertensive treatment of hypertension. The human circadian biorhythm changes the therapeutic effect of antihypertensive drugs by affecting the pharmacokinetics and pharmacodynamics; at the same time, following the human blood pressure rhythm in the treatment of hypertension can reduce the risk of target organ damage and cardiovascular and cerebrovascular events. Therefore, in the treatment of hypertension, the administration time and drug dosage should be adjusted according to the pharmacochronology to obtain the best curative effect and minimal side effects, and reduce the occurrence of adverse reactions and complications.
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Chronopharmacology aims at the use of biological rhythms in the clinical treatment to enhance both effectiveness and tolerance and minimizes the side effects of a drug by determining the best biological time for its administration. It involves bot h the investigation of drug effects as a function of biologic timing and the investigation of drug effects upon rhythm characteristics. Rhythmicity has been detected in several physiological variables such as pulse, temperature, blood pressure and hormonal secretions like diurnal variation insulin effects on blood glucose. The goal of chronopharmacology is to optimize the therapeutic effect and control or reduce the adverse effects without altering the functioning of the drug in the body. Auto-induction, auto- inhibition and food effects are considered to be the reasons of chronopharmacology. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24 hrs rhythm of biological, physiological and behavioral processes under the control of the circadian clock. Now a day, the chronopharmacological principle is used in the therapy of various diseases such as angina, hypertension, asthma, peptic ulcer, diabetes, migraine, etc. This article aims to introduce chronopharmacology, their terminologies, causes and need of it, biological clock and biological rhythms in various biological systems and the dependence of diseases on biological rhythms.
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OBJECTIVE:To provide reference for further promoting the clinical application of chronopharmacology and rational drug use.METHODS:The self-designed questionnairea was used to conduct on-site investigation among participants from 40 hospitals in Anhui province by dint of a meeting.The survey data were analyzed statistically.RESULTS:Totally 170 questionnaires were distributed,and 166 were retrieved,the total response rate was 97.65％.93.37％ of the interviewed pharmacists were aware of the circadian rhythms,and 87.35％ were aware of the circadian rhythms of more than two kinds;interviewed pharmacists expressed better awareness of indicators like gastric acid secretion (75.30％),blood pressure (67.47％) and growth hormone (66.87％) etc.while their awareness of other diseases like anaphylactic rhinitis (66.87％),gastric ulcer (50.60％) and migraine (50.00％) remained to improve.All the interviewed pharmacists recognized the better therapeutic efficacy (84.34％) and lower side effect (81.33％) of chronopharmacology-referred medication;chronopharmacology characteristics of glucocorticoid drugs were best known (34.34％),followed by antihypertensive drugs (25.30％).CONCLUSIONS:Pharmacists in Anhui province have certain knowledge of chronopharmacology such as biological rhythms,biological process or indicators,biological rhythms of disease and advantage of chronopharmacology-referred medication.It indicates that there has been a foundation for popularizing the concept of chronopharmacology in clinical medication in China;but not often contacted physiological processes or indexes,the understanding of biological rhythm of uncommon diseases are still insufficient,and the understanding of chronopharmacology characteristics of various drugs are far from ideal.
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La cronobiología es la disciplina que ha estudiado la organización temporal de los procesos que ocurren en los seres vivos, los mecanismos que las originan y sus alteraciones. En 1832, Agustín de Candolle demostró que bajo condiciones constantes el período de los ciclos de movimientos de las plantas duraba unas 24 horas, con lo que añadió una evidencia de la naturaleza endógena de los ritmos biológicos. En los mamíferos, se ha estimado que aproximadamente el 10 por ciento del genoma está bajo un control circadiano. Desde la década de los años 70´s se observó que la respuesta inmune dependía de la hora del día en la cual se analizaba y que la susceptibilidad a las infecciones dependía también de la hora en la cual el organismo fuera infectado. Recientemente se ha establecido una relación entre el ciclo circadiano y la respuesta inmune. Este trabajo trata las ventajas del conocimiento del ritmo circadiana de los mecanismos inmunitarios y la importancia del uso de la cronoterapia sobre los osciladores de las células del sistema inmune en los trastornos inmunitarios, lo cual pudiera evitar complicaciones en los pacientes(AU)
Chronobiology is the science that studies temporary organization of the processes that happen in organisms, the mechanisms that originate them and its disorders. Austin of Candolle demonstrated that under constant conditions the period of the cycles of the plants' movements it lasted some 24 hour, adding an evidence of the endogenous nature of the biological rhythms in 1832. In mammals, has been considered approximately 10 percent of genome under circadian control. Since decade of 70´s, was observed that immune response depends of day´s hours in which it was analyzed, and the susceptibility to infections also depends of the hour in which an organism is infected. It has begun to establish relationship between circadian cycle and immune response recently. This work intends to give us the advantages of the knowledge of circadian rhythms of immune mechanisms and the importance of the chronotherapy´s use on the oscillators of the immune system´s cells in immunity dysfunctions and it would avoid complications in the patients(AU)
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Humans , Chronobiology Discipline/methods , Immune System , Chronotherapy/methodsABSTRACT
Resumen Los grandes avances científicos en diversas áreas biomédicas, así como sus demandas de conocimiento y dedicación, han alejado al investigador de la cama del paciente y, por su parte, el clínico poco a poco se trasforma en un técnico en atención médica, y deja de lado el conocimiento científico. Es así como nace la necesidad de unir la investigación básica y la clínica, es decir, trasladar los hallazgos del laboratorio a la medicina clínica. La medicina traslacional surge para darle continuidad a la medicina basada en evidencias, obtenidas en los laboratorios. Sin embargo, la investigación biomédica básica no se limita a la metabolómica, la proteómica, la terapia génica o a la nanotecnología, por mencionar algunas líneas de investigación; existen otras mucho más sencillas, pero no por esto menos importantes. El estudio de los ritmos biológicos es un claro ejemplo donde se ha logrado establecer el puente de transmisión y aplicación de la ciencia básica a la aplicación a problemas de salud. La cronomedicina propone un mejor entendimiento y manipulación de la fisiología, utilizando sus variaciones circadianas como parte del diagnóstico y tratamiento de algunas patologías.
Abstract The major scientific advances in various biomedical areas as well as its demands for knowledge and dedication have moved away the researcher from of the patient's bedside, and the clinician is gradually been transformed into a technician in medical care, leaving aside the scientific knowledge. Therefore the need to join the basic research and the clinic arose and to translate the findings of the laboratory to clinical medicine was born. The translational medicine appeared to give continuity to the evidence-based medicine obtained in the laboratory. However the basic biomedical research is not limited to metabolomics, proteomics, gene therapy or nanotechnology, just to mention a few research lines, some of these are much easier but are not less important. The study of biological rhythms is a clear example of successfully setting up the bridge between transmission and the application of basic science applied to health problems. The chronomedicine proposes a better understanding and manipulation of the physiology, using circadian variations as part of the diagnosis and treatment of certain pathologies.
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Chronopharmacology aims at the use of biological rhythms in the clinical treatment so as to enhance both effectiveness and tolerance and minimize the side effects of a drug by determining the best biological time for its administration. Chronopharmacology is useful to solve problems of drug optimization. In the human organs, the metabolic fate of a pharmacologic agent as well is not constant as a function of time. Thus, the chronobiological approach of drug administration involves a lesser risk of errors than the conventional homeostatic approach. Chronopharmacology is now used as a routine to treat various disorders like hypertension, angina, cancer and various psychotic disorders. The newer drug delivery systems that are designed with the chronopharmacological approach hold great scope for delivering better patient care in terms of efficacy, tolerance and safety parameters of the drug. This review aims at introducing chronopharmacology, the role of the regulatory system of biological clock in pharmacotherapy and the benefits it has conferred in various clinical conditions.
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Biological Clocks/physiology , Circadian Clocks/drug effects , Circadian Rhythm/drug effects , Drug Chronotherapy , Humans , PharmacologyABSTRACT
Objective To investigate the regularity of chronopharmacology of bruceolic oil emulsion ( BOE) in treating H22 tumor-bearing mice. Methods The KM mice model bearing H22 hepatocellular carcinoma was established. And then the model mice were divided into groups according to the condition of illumination and medicine intervention. After treatment for 10 days, the tumor-growth inhibitory rate, viscera indexes, and hepatic and renal function indexes were observed. Results Tumor mass and ratio of tumor mass to body mass were decreased in medication groups under the normal and disordered illumination. The tumor mass and ratio in mice treated with BOE before dark phase of normal illumination and disordered illumination, and during the dark phase of disordered illumination differed from those of the model group at the corresponding illumination phase (P<0.05) . Under normal illumination, BOE-treated mice at 10 pm of dark phase had lower liver index but higher thymus index than the model group (P < 0.05) . Under disordered illumination, BOE-treated mice at 7 am of dark phase had higher spleen index than the model group ( P < 0.05) . Conclusion BOE exerts certain inhibition of H22 hepatocellular carcinoma under both normal illumination and disordered illumination, and the effect will be better when medication is given in dark phase period.
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Under physiological conditions, many vital functions of the body are controlled by transient release of bioactive substances at a specific time and site. Based on the circadian rhythm character of disease and chronotherapeutic conceptions, pulsatile delivery system has been designed to achieve optimal therapeutic effect and reduce the toxic and side-effect. In recent years, more and more studies are focused on the pulsatile multiparticulate drug delivery system. Pulsatile multiparticulate system possesses many benefits, such as no risk of dose dumping, predictable gastric emptying, flexible release patterns and increased bioavailability. Based on these premises, the aim of this review is to summarize the major design methods of pulsatile multiparticulate and the research progress.
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Under physiological conditions, many vital functions of the body are controlled by transient release of bioactive substances at a specific time and site. Based on the circadian rhythm character of disease and chronotherapeutic conceptions, pulsatile delivery system has been designed to achieve optimal therapeutic effect and reduce the toxic and side-effect. In recent years, more and more studies are focused on the pulsatile multiparticulate drug delivery system. Pulsatile multiparticulate system possesses many benefits, such as no risk of dose dumping, predictable gastric emptying, flexible release patterns and increased bioavailability. Based on these premises, the aim of this review is to summarize the major design methods of pulsatile multiparticulate and the research progress.
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OBJECTIVE To investigate the effect of the dosing time on the pharmacokinetics oferlotinib.METHODS Female C57BL mice were contained under standardized 12h light/dark circadianconditions (lights on at 7:00,off at 19:00)for 3 weeks and randomly assigned into six groups.Erlotinibhydrochloride was orally administrated to the mice in each group at 8:00,12:00,16:00,20:00,24:00and 4:00,respectively.Blood was drawn from the eyeballs of the mice at 12 different time points aftereach administration.The plasma concentration of erlotinib was determined through a high-performanceliquid-chromatographic assay and the parameters were calculated by WinNonlin. RESULTSThe area under curre (AUC)and mean residence time (MRT)of these groups were apparently differ-ent.AUC0 ~24 h and MRT0 ~24 h were the lowest in the 20:00 administration group as compared to othergroups (P<0.01 ).Tmax of the 20:00,24:00 and 4:00 groups was apparently higher than that of the8:00 and 12:00 groups (P<0.01 ).The clearance of the light phase groups was lower than that of thedark phase groups (P<0.01 ),with the highest in the 20:00 group.The peak value of cmax appeared inthe 12:00 group and the lowest in the 20:00 group (P<0.01 ).CONCLUSION Circadian rhythm playsa critical role in pharmacokinetics of erlotinib in mice.
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Objective To explore the influence of different administration time on antidepressant effect of seven clinical common antidepressants. Methods Male mice were randomly divided into eight groups:venlafaxine (75 mg/kg), sertraline (20 mg/kg), fluoxetine (20 mg/kg), doxepin (15 mg/kg), mirtazapine (15 mg/kg), citalopram (40 mg/kg), trazodo?ne (50 mg/kg) and control (saline) groups. Each group contained 36 mice. Drugs were administered to 6 mice per group 30 min before forced swimming test at the 6 time points (9:00, 13:00 and 17:00 as light phase and 21:00, 1:00 and 5:00 as dark phase). Forced swimming test was applied to determine the influence of dosing time on anti-immobility effect of seven antidepressants at each time point. Results Immobility time in venlafaxine group and sertraline group significant?ly decreased compared with that of control group at all time points(all P<0.05). Moreover, anti-immobility effects of ven?lafaxine, fluoxetine, mirtazapine and doxepin were better during the dark phase than during the light phase (all P<0.05). In addition, immobility time in sertraline group decreased at the late part of dark phase (5:00) and the early part of light phase (9:00) compared with other phases (P<0.05). Conclusions Most antidepressants show 24-h rhythm dependent an?ti-immobility effects, but rhythmic patterns are not completely consistent among different antidepressants. Further study is needed to explore the chronopharmacological mechanism and clinical applications of these antidepressants.
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Circadian rhythm is a global phenomenon, the control mechanisms of which are manifested at every level of biological organization, from genes and intracellular mechanisms to networks of cell populations, and to all central neuronal systems at the organismic level. In pharmacotherapy, the pharmacokinetic parameters such as drug absorption and distribution, drug metabolism, and renal elimination show diurnal variations. The symptoms and signs in diseases like asthma, myocardiac infarction, angina pectoris, hypertension and stroke also show diurnal fluctuations. These observations require drug treatment considering the circadian rhythm of body function and disease. Circadian time has to be taken into account as an important variable influencing a drug's pharmacokinetics and/or its effects or side effects in clinical practice.
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Absorption , Angina Pectoris , Asthma , Circadian Rhythm , Clinical Medicine , Drug Therapy , Hypertension , Infarction , Metabolism , Neurons , Pharmacokinetics , StrokeABSTRACT
0.05) but the incidence of toxicities in Group B was higher than in the other two groups. CONCLUSION:Comparatively speaking,Gemcitabine administered at 8 ∶ 00 was proved to be safer and more effective as compared with the other two groups in the treatment of NSCLC.