CHRONOPHARMACOLOGY: THE BIOLOGICAL CLOCK

CHRONOPHARMACOLOGY: THE BIOLOGICAL CLOCK

Salman Kapadia, Vanita Kanase ^*, Shalaka Kadam, Priya Gupta and Vishwavibhushitam Yadav

Department of Pharmacology, Oriental College of Pharmacy, Sanpada, Navi Mumbai - 400705, Maharashtra, India.

ABSTRACT: Chronopharmacology is the science that is of different types in the pharmacological activities of different treatment over organic timings and endogenous balance. Chronotherapeutics is the science which increases the creativity and security of prescriptions by balancing their fixations during the 24 h synchronizing with regular routine determinants of disease. Chronopharmacokinetics again manages time and predictable changes in pharmacokinetic parameters of medicines. For example manages the examination of the fleeting changes in the assimilation, dissemination, digestion, and disposal because of the time of planning of the treatment. Circadian rhythms are especially notable in drugs. Biologic rhythms are the endogenic nature of circadian. Chronopharmaceutics is depicted as a part of pharmaceutics gave to the plan and evaluation of medication prescribing structure that discharges a bioactive specialist at a musicality that preferably coordinates the natural prerequisite of given disease treatment. The fresher treatment conveyance structure that is structured with the chronopharmacological approach holds incredibly long for conveying better patient consideration regarding viability, resistance, and wellbeing parameters of the medication.

Chronopharmacology, Chrono-biology, Chronopharmacokinetics, Chronopharmacotherapy, Circadian rhythm

INTRODUCTION: Chronopharmacology is the discipline that states how the effect of treatment changes with time and endogenous regularity. The objective is to improve our comprehension of intermittent and consequently predictable changes in both wanted impacts Chrono adequacy and Chrono resistance of prescriptions ¹. Chronopharmaceutics is a part of pharmaceutics (science and innovation of medication measurement shapes) intended to the plan and assessment of drugs movement structure that discharges a bioactive specialist at a mood that in a perfect world matches the organic necessity for a given disorders treatment or counteractive action continuously.

Chronopharmaceutics Drug Delivery System utilizes the essential ideas of human chronobiology and the beat reliance on certain sickness states and the pharmacodynamics of prescriptions ². Chrono-pharmacokinetics is characterized as dosing time dependent on what is more, unsurprising rhythm varieties in parameters used to describe the pharmacokinetics of therapy ³. Chronopharma-cokinetics of a particular medication may comprise changes from a mono-to a multi-compartmental model as a component of drug dosing time ⁴.

Chronopharmacokinetics of medications have been approved for some, species including people, with both intense and mild organization even for continued discharge arrangements having a half-life (t½) up to 84 h ⁵. Chronotherapeutics is the control worried about the movement of medications as per the inborn exercises of sickness over a specific timeframe on the grounds that the biochemical, physiological, and neurotic varieties over a 24 h period in people have happened ⁶. The science managing with the occurrence of organic rhythmicity in living life form is called chronobiology. The branch controlling the pharmacological parts of chronobiology is named as Chronopharmacology, which might be subdivided into chronotherapy, chronopharma-cokinetics, and Chrono poisonous quality ⁷. Chronotherapeutics includes a treatment strategy wherein in-vivo medication accessibility is coordinated to coordinate rhythms of sickness so as to improve remedial results and prevent symptoms. It depends on the idea that there is an independent connection between top to through rhythm movement in disorders indications and hazards factors, pharmacologic affectability and pharmacokinetics of numerous medications take in to account predictable organization time sub-ordinate variety in the pharmacokinetics of medicates just as the weakness because of transient association of physiochemical process and capacity of body as circadian and others rhythms ⁸.

Circadian Rhythm: Circadian rhythm, likewise called a natural mood, is characterized as motions in the natural, physiological, and social capacity of a creature with a periodicity of 24 h. Circadian rhythms are endogenous in nature and are known to persevere under free-running conditions. Infections, for example, hypertension, dead myocardial tissue (MI), congestive heart disappointment, and stroke, pursue the body's circadian rhythm ⁹. It might likewise be significant in impacting the reactions to different meds. The malady event is free of time of day, month, or year. Therefore, the time when meds are directed is anything but a key concentration for medicinal services experts in conclusion or recommending ¹⁰. Comprehension of the atomic control of circadian rhythms and resulting flagging pathways has taken into consideration new restorative medication focuses on being recognized. Thus, a superior comprehension of how to all the more effectually and securely uses current medications ¹¹. A consistent combination of medicines is an accepted method for accomplishing steadiness in helpful impact and medication wellbeing ¹².

Clinical investigations demonstrate that the extent of the anticipated in-time (musical) contrasts can be incredible to the point that it tends to be a solid determinant of time during 24 h, serious sullen and mortal occasions happen and when the indications and indications of numerous unending ailments flare. Thus, circadian time must be considered as a significant variable affecting a medication's pharmacokinetics and its belongings or symptoms ¹³.

Biologic rhythms are the endogenous nature of circadian. The absence of outer synchronizers prompts free-running rhythms. The time of free-running rhythms is longer or shorter than 24 h and is a trademark for every species. Our inner timekeepers are hereditarily determined ¹⁴. Circadian checks are available in many creatures and negotiate the transaction between the earth; furthermore, physiologic procedures ¹⁵. Typically, rhythms modify physiologic reactions to foreseen boosts times. Interruption of circadian rhythms worsens a few endless sicknesses. The "focal" circadian pacemaker is in the suprachiasmatic core in the nerve center and is in charge of organic rhythms managed by the light / dull cycle (LDC). Fringe tissues show circadian motions that are facilitated by the focal pacemaker ¹⁶.

Most, if not all, light-touchy creatures, including warm-blooded animals, have an ace circadian clock that manages physiological and social procedures in arrangement with the 24-h day. Late advances in understanding the atomic control of circadian rhythms and ensuing flagging pathways have taken into account new remedial focuses to be recognized as the ability of how to all the more viably use of recent medications. Notwithstanding assuming a key job in typical physiology and conduct, distortions in the circadian mood are related to the pathophysiology of sicknesses, including diabetes, cardiovascular ailment, mental scatters, and different immune system maladies/inflammation ^17-21.

Circadian Immune Regulation: A second unmistakable pharmacological focus with solid circadian guidelines is the resistant framework. Be that as it may, late research demonstrates that cell-self-sufficient timekeepers inside insusceptible cells themselves direct variety in an extensive number of circadian safe parameters. For instance, the reaction of T-cells to encourage shifts in circadian design ²² and macrophages; thus, revive insusceptible reactions in similarly diurnal design with their own rhythm. ²³

The outcomes of the inescapable circadian guideline of invulnerable capacity are various and run a long ways past the previously mentioned diurnal variety in infective weakness. For instance, an articulated circadian movement of blood coagulating has been known for quite some time and is upheld by circadian variety in components going from platelet total and bond ²⁴ to genuine articulation of clotting components like PAI^{-1 25}. Circadian clock likewise direct course of numerous invulnerable cells, for example, hematopoietic immature microorganisms ²⁶ At long last, circadian resistant guideline brings about diurnal varieties in related insusceptible parameters like aggravation, which assumes a solid job in circadian variety in numerous infections ²⁷.

Chronopharmacotherapy in Various Diseases:

Cardiovascular Disease: Various parts of the human body locate step by step, and these kinds of variation cause the development in both infection state and in plasma steady center ²⁸. Cardiovascular capacities, for example, pulse and circulatory strain, show 24 h variety. The frequency of cardiovascular disorder, for example, intense myocardial localized necrosis, strokes, and arrhythmia likewise show clear diurnal movement since a large portion of these can activate deadly or serious results. It is critical to clarify the exact system of the beginning of these infections ²⁹. The distinctions in examples of sickness among day and night for the cardiovascular issue, for example, hypertension, angina, heart assault, abrupt cardiovascular passing, and stroke, have been recorded.

The Chronotherapeutics approach gives progressively exact assurance of when patients are at most noteworthy hazards and in most noteworthy need of treatment. For instance – it has regularly been discovered that the pulse of hypertensive patient increments quickly in the first part of the day in the wake of enlivening, commonly tops in the center to late time, diminishes at night, and is most reduced while the patient rests around evening time. It might likewise be essential to perceive that the danger of heart assault gives off an impression of being most prominent during the early morning hours in the wake of enlivening. For example, hair-like opposition and vascular reactivity are higher toward the beginning of the day and diminishes later in the day. Platelet suitability is expanded, and fibrinolytic movement is died in the first part of the day, prompting a condition of relative hypercoagulability of the blood. Heartbeat is minimal during medication, and it rises during the early morning time. Numerous antihypertensive medications do not control the early morning pulse when given once every day promptly toward the beginning of the day

Common onset Time of Cardiovascular System:

Asthma: It is portrayed by airway route aggravation coming about in hyperresponsiveness of lower respiratory tract to different natural upgrades. Airway route opposition increments dynamically during the evening in the patient. Asthma is a very famous sickness wherein the wide circadian variety happens regarding time. There is an expanded rate of asthma during the early-morning h. The manifestations of asthma happen 50 to multiple times more during the evening.

The fuel of asthma during the night speaks to the changing status of natural working because of circadian rhythms in bronchial patency; airway routes are hyperactive to acetylcholine, histamine, and house residue and plasma cortisol, epinephrine, histamine, and cyclic AMP. When day by day dosing of breathed in glucocorticosteroid ciclesonide, supported discharge theophylline, transdermal tulobuterol fix observed to be powerful if there should arise an occurrence of nighttime asthma ³⁰.

Cancer: Human and creature studies recommend that chemotherapy might be increasingly powerful and less harmful if malignancy medications are directed cautiously at chosen times that exploit tumor cell cycles while less poisonous to ordinary tissue. The rhythm circadian changes in the tumor bloodstream and malignant growth development are significant both when tumors are little and becoming most quickly and when they are bigger and developing all the more gradually.

Circadian chemotherapy timing genuinely influences sedative effect examples and seriousness, most extreme infected portion, normal portion power, tumor reaction standard, and the outlast of a sufferer with malignant swelling.

The pharmacologic and pharmacokinetic properties of the medication, rhythm changes in DNA and RNA blend, RNA translational action and mitotic movement may impact tumor cell vulnerably. The disease chronogenetic treatment is observed to be powerful in tumour concealment in-vivo. For instance, it has been demonstrated that CLOCK qualities direct affectability of the anticancer medication cyclophosphamide ^{31, 32}.

Peptic Ulcer: Huge numbers of the elements of the gastrointestinal tract are liable to circadian rhythms: corrosive gastric discharge is more during the evening. While gastric, little inside motility and gastric exhausting are all slower around evening time. Concealment of night time erosive is a significant factor in duodenal ulcer treatment. Along these lines, for dynamic duodenal ulcer, when every day at sleep time is the prescribed dose routine for H₂ adversaries. Sleep time H₂‐receptor bar uses Chronotherapy rhythm issues of supported or significant decrease of 24‐h intragastric sharpness, including the risk of enteric contamination ³³.

Diabetes: In sort, I diabetes the circadian musicality of insulin, and its development is of physiologic interest and clinical superiority. In this way, insulin is discharged in pulsatile style; however, once in a while; it is periodic. Insulin can exhibit its circadian rhythm of 8-30 min, which can display its perfect activity.

The modulators of insulin discharge and activity are emitted in a circadian example and attract the method of insulin discharge. So contrast among most extreme and least plasma insulin fixation has transient rhythmicity, and complex optional circadian musicality is variable early-morning and late-evening insulin obstruction ³⁴.

Chronopharmacology of Arthritis: Rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and gout exhibit profound circadian rhythm in manifestations and intensity of symptoms.

Rheumatoid Joint Inflammation (RA): It is a continuous blazing immune system issue with indications of solidness, swelling, and trauma of at least one joint. The severity of these is multiple times more somewhere in the range from 08:00 to 11:00 am. Long-acting NSAIDs like flurbiprofen, ketoprofen, indomethacin at sleep time guarantee satisfactory control of morning indications of RA. Ibuprofen, non-acetylated salicylates, and various other nonsteroidal anti-inflammatory drugs (NSAIDs) are utilized in rheumatoid joint pain (RA) patients to diminish joint aggravation and improve work. Proportionate dosages of ibuprofen and of non-acetylated salicylates are similarly mitigating in RA ³⁵.

Pain is Increasingly Extreme Between 2 p.m. What's More, 8 pm: The torment for some timeframe fluctuates from individual to person. If when the agony is more around night time, evening segment is endorsed at this point in case injury is most horrible in the night, morning bit is proposed. Individualized chronotherapy is fundamental, as once per day ketoprofen, indomethacin is prescribed to time of day when trauma is most exceedingly terrible. Strong scattering of ketoprofen was observed to be increasingly powerful in the hindering movement of RA. The defensive impact of ketoprofen and its strong scattering was fundamentally higher when these were regulated at 0800 h ³⁶.

Need for Chronopharmacotherapy: Chrono-pharmacology is required to screen treatment in order to restrain the term of treatment, particularly in situations where patients are as of now having bargained renal, heart, and hepatic or some other capacity of the body. Any sort of collection of medications in these organs causes more noteworthy harmfulness, which may be prompted to reduce the capacity of the organ. In this manner, chronopharmacotherapy turns into a significant piece of the treatment of a few infections, especially those affecting focused on body parts ³⁷. As per the 1996 American restorative affiliation survey, more thought of chronotherapy in clinical preliminaries is exceptionally invited by the entire medicinal network. The aftereffect of the review demonstrated that 75 percent of the specialists are agreeable to the patient's circadian or day by day rhythm arranged treatment ³⁸.

From the different examinations, it is shaped that numerous cardiovascular occasions, including myocardial dead tissue, stroke, and unexpected passing, happen during the underlying long periods of morning movement between 6 am, which is more, 12 noon afternoon. Furthermore, this is a lot higher during this period than other planning during the day. Circulatory strain demonstrates a sharp top in the early morning, significantly agreeing with the crest for cardiovascular occasions and a stretched out during the night ³⁹. In the meantime, pulse increments in the late morning or early evening ⁴⁰. In our investigation, most extreme doctors were recommending the drug as chronopharmacologically it can profit the patient however to the extent PPIs (Proton pump inhibitors) were concerned doctor endorsed them before breakfast as opposed to endorsing it at sleep time. This demonstrates the chronopharmacological approach is yet to be implemented in the clinical practice.

Chronopharmacokinetics:

Absorption: In people, for orally directed medications, assimilation was demonstrated to be influenced by circadian rhythm as corrosive gastric emission and gastric pH, gastric motility, exhausting gastric time, and gastrointestinal bloodstream change as indicated by the season of day ^{41, 42}. These progressions may affect the time-subordinate distinction of medication assimilation. Then again, exhausting gastric time is another significant factor in the retention of medications. Gastric eradication rates were thought about between 8:00 am to 8:00 pm in male subjects, and it was discovered that gastric discharging (t½) for the night supper was essentially longer for solids yet not for fluids contrasted and those of the morning meal ⁴³.

The expansion in night meal gastric discharging time may likewise cause a postponement in achieving top plasma fixations for a few medications. Such varieties might be identified with the physicochemical properties of a medication, since most lipophilic medications appear to be consumed quicker in the first part of the day when contrasted with night ^{44, 45}. The systems basic the chronokinetics of lipophilic medications include a quicker gastric discharging time and higher gastrointestinal perfusion in the first part of the day ⁴⁶.

Distribution: In natural liquids and tissues, circadian changes identified with medication dispersion are appeared to change as per the time of day ⁴⁷. Bloodstream relies upon a few administrative elements, including the thoughtful and parasympathetic frameworks whose exercises are known to be circadian time-dependent with a dominating diurnal impact of the thoughtful structure ⁴⁸. Therefore, daytime increments and evening diminish the bloodstream, and nearby tissue bloodstreams may clarify a conceivable contrast in medication appropriation relying upon dosing time ^{49, 50}.

Most human plasma protein fixations, including egg whites and a1-glycoprotein, collapse down to their least during the evening time, increment by day, and reach to most around early afternoon. Subsequently, everyday varieties have been accounted for medication protein authoritative. Touitou et al., (1986) have demonstrated that in youthful solid grown-up subjects, the circadian abundance of plasma protein was fairly little (8-15%) contrasted and that of sound old subjects (normal age ~ 75 yr).

A noteworthy night time fall was watched for the last mentioned (circadian adequacy of 20%), an outcome which recommends that the free part of medications typically bound to plasma proteins increments during the nighttime rest as a component of maturing ⁵¹. The impacts of circadian rhythm on the plasma protein authoritative of medications were first shown for cortisol, which spans to its most noteworthy level around early afternoon.

Moreover, the engineered analogs for cortisol were indicated to be impacted by circadian mood ^{52, 53}. P-glycoprotein, the result of the multidrug opposition (MDO) quality which adds to renal, biliary and intestinal disposal of medications, and the intestinal H(+) / peptide co-transporter 1 (PEPT1) assume significant jobs as a supplement and medication transporter work as a xenobiotic transporter and display 24 h variety ^{54, 55}. From a toxicological perspective, drugs with a little volume of dissemination and additionally high protein-restricting limit and medications which have a tight remedial record might be influenced by the progressions in circadian rhythm and wrong dosing of such medications in evening time may cause direct lethality.

Metabolism: Hepatic medicines digestion appears to rely upon liver xenobiotic-using protein movement or potentially hepatic bloodstream ^{56, 57}. Circadian rhythm can influence the bloodstream in the liver and, in this way, can influence the liberty of a few medications, including propranolol ⁵⁸. In well-evolved creatures, a large portion of the xenobiotics is utilized in, for the most part, in the liver. Be that as it may, there is moreover extrahepatic metabolism in the cerebrum, kidney, lung, and different tissues. Xenobiotic digestion is made out of three gatherings of proteins with unmistakable capacities. The stage I gathering contains the microsomal cytochrome P450 (CYP450) catalysts. Stage II, or conjugating compounds, involves sulfotransferases (SULT), UDP-glucuronotransferases (UGT), NAD (P) H quinine oxidoreductases (NQO), epoxide hydrolases (EPH), glutathione-S-transferases (GST) and N-acetyltransferases (NAT). Conjugation gives the lipophilic mixes to be hydrophilic enough in this way control and encourage their discharge into bile, feces, and additionally urine.

After stage II reactions, the xenobiotic conjugates can apply to organize III reactions ^{59, 60, 61}. Few kinds of oxidative reactions catalyzed by the CYP450 compounds been accounted for substrates, for example, aminopyrine, paranitroanisole, hexobarbital and 4-dimethy-aminobenzene, aniline, benzphetamine, benzpyrene and imipramine ^{62, 63}. It appears that medication digestion coming because of oxidative microsomal responses achieves its crest during the action range and it's most minimal during the relaxation period. On the contrary, sulfate conjugations are a lot faster during rest than during the action period ⁶⁴.

Excretion: The circadian planning framework assumes a key job in the progressions of the lethality of medications by affecting their digestion systems in the liver and digestive system, notwithstanding their discharge by means of bile stream and urine. Rodents with endless biliary waste under an unbending lighting plan (light on at 6 am and off at 6 pm) displayed a noteworthy circadian rhythm of bile stream, biliary obsession, and evacuative amount of bile salts, cholesterol and phospholipids ⁶⁵. Then again, the discharge rates of these polyamines were found to be most elevated toward the beginning of the day in sound volunteer subjects ⁶⁶. A gigantic decrease in the rate and level of ciprofloxacin release following 10 pm association was distinguished ⁶⁷. The excretion of 17-oxosteroids was likewise indicated to be impacted by circadian clock ⁶⁸.

Advantages of Chronopharmacotherapy:

1. It counteracts an overdosing of any class of medication.
2. It makes the use of the medication progressively proper, and in this manner, the estimation of a medication is expanded.
3. It decreases the symptoms of medication and aides in minding out the treatment for just a specific or constrained timeframe ⁶⁹.

Disadvantages of Chronopharmacotherapy:

1. It builds up a non 24 h rest wake disorder after the treatment as the individual doses for more than 24 h during the treatment. It's not exactly normal, but rather, the level of hazard is not known.
2. An individual may likewise be denied of rest now and then.
3. The individual turns out to be less profitable during chronotherapy and remaining alert till the other timetable may be a bit awkward.
4. The patient should take a break from the busy schedule calendar as its time taking treatment.
5. Therapeutic supervision is compulsory for this treatment, and customary counseling of rest pros is prescribed.
6. Individual needs to keep himself wakeful till the following rest plan so he needs to get himself occupied with the goal that he remains alert till the other calendar.
7. Individuals experiencing treatment may feel curiously hot or cold now and then.
8. Patient needs to counsel the specialist routinely to prevent reactions ^{70, 71}.

Ideal Characteristics of Chronopharmaco-therapy:

1. It is non-toxic inside affirmed cut-off points of utilization.
2. It should have a real‐time and explicit activating biomarker for a given ailment state.
3. It ought to have a criticism control framework (for example, self-regulated an adaptative capacity to circadian mood and individual patient to separate between conscious – rest status).
4. It is Biocompatible and biodegradable, particularly for the parenteral organization.
5. It is Simple to fabricate at the financial expense.
6. It is Simple to control into patients so as to upgrade consistency to measurement routine ⁷².

CONCLUSION: The importance of this article is to educate scholars, physicians, pharmaceutical researchers, and other experts about the seriousness of organic timekeepers and Chronopharmacology to human wellbeing and infection additionally inspire the agent to grow new devices for the treatment of various maladies. The regularly growing field of chrono-pharmacology has opened numerous entryways in innovative work for structuring better approaches to adjust and oversee the treatment for different illnesses. So, as to make an interpretation of research information into clinical application, noteworthy advancement in the portrayal of circadian varieties in protein articulation and action in people is totally vital.

In this manner, the information of chrono-pharmacology isn't constrained to the scholars, pharmacologists and researchers yet in addition to clinicians so that there is the better conveyance of patient consideration.

ACKNOWLEDGEMENT: The author thanks his guide Dr. (Mrs.) Vanita Kanase for constantly supporting and every colleague who supported during the work.

CONFLICTS OF INTEREST: No conflicts of interest between any of the authors.

REFERENCES:

1. http://www.annualreviews.org/doi/abs/10.1146/annurev.pa.32.040192.000411?journalCode=pharmtox.
2. Patel G: Specialized chronotherapeutic drug delivery systems, Pharmainfo.net
3. Ohdo S, Koyanagi S, Matsunaga N and Hamdan A: Molecular basis of chronopharmaceutics. J Pharm Sci 2011; 100: 3560-76.
4. Baraldo M: The influence of circadian rhythms on the kinetics of drugs in humans. Expert Opin Drug Metab Toxicol 2008; 4: 175-92.
5. Ohdo S, Koyanagi S, Matsunaga N and Hamdan A: Molecular basis of chronopharmaceutics. J Pharm Sci 2011; 100: 3560-76.
6. Sarasija S and Hota A: Colon-specific drug delivery systems. Ind J Pharm Sci 2002; 62(1):1-8.
7. Pandit V and Suresh S: Emerging role of biorhythms in optimizing treatment of disease. Indian. J Novel Drug Delivery 2009; 1: 2-10.
8. Devdhawala MG and Seth AK: Current status of Chronopharmatherapeutic drug delivery system: an overview. J Chem Res 2010; 2(3): 312-28.
9. Mehul DG and Avinash SK: Current status of chrono-therapeutic drug delivery system: an overview. J Chem Pharm Res 2010; 2: 312-28.
10. Smolensky MH, Lemmer B and Reinberg AE: Chronobiology and chronotherapy of allergic rhinitis and bronchial asthma. Adv Drug Deliv Rev 2007; 59: 852-82.
11. Ohdo S: Biological clock and chronopharmacology. Nihon Shinkei Seishin Yakurigaku Zasshi 2007; 27: 95-02.
12. Reinberg A: Clinical chronopharmacology. Concepts, kinetics, application. Br J Clin Pharmacol 1991; 32: 255.
13. Smolensky MH, Peppas NA: Chronobiology, drug delivery and chronotherapeutics. Adv Drug Deliv Rev 2007; 59: 828-51.
14. Fujimura A Tateishi T, Ohashi K and Ebihara A: Differences of chronopharmacokinetic profiles between propranolol and atenolol in hypertensive patients. J Clin Pharmacol 1993: 756-61.
15. Hogenesch JB and Herzog ED: Intracellular and intercellular processes determine robustness of the circadian clock. FEBS Lett 2011; 585: 1427-34
16. Mohawk JA, Green CB and Takahashi JS: Central and peripheral circadian clocks in mammals. Annu Rev Neurosci 2012; 35: 445-62.
17. Rybak YE, McNeely HE, Mackenzie BE, Jain UR and Levitan RD: Compr Psychiatry 2007; 48: 562.
18. Levi F and Schibler U: Annu Rev Pharmacol Toxicol 2007; 47: 593.
19. Solt LA, Wang Y, Banerjee S, Hughes T, Kojetin DJ, Lundasen T, Shin Y, Liu J, Cameron MD, Noel R, Yoo S-H, Takahashi JS, Butler AA, Kamenecka TM and Burris TP: Nature 2012; 485: 62.
20. Ohdo S: Biol Pharm Bull 2010; 33: 159.
21. Sprouse J: Expert Opin Ther Targets 2004; 8: 25.
22. Fortier EE, Rooney J, Dardente H, Hardy MP, Labrecque N and Cermakian N: Circadian variation of the response of T cells to antigen. J of Immunology 2011; 187: 6291-00.
23. Keller M, Mazuch J, Abraham U, Eom GD and Herzog ED: A circadian clock in macrophages controls inflammatory immune responses. proceedings of the National Acad of Sci of the USA 2009; 106: 21407-12.
24. Fujimura A, Ohashi K and Ebihara A: Daily variations in platelet aggregation and adhesion in healthy subjects. Life Sciences 1992; 50: 1043-7.
25. Kluft C, Jie AF, Rijken DC and Verheijen JH: Daytime fluctuations in blood of tissue-type plasminogen activator (t-PA) and its fast-acting inhibitor (PAI-1). Thrombosis and Haemostasis 1988; 59: 329-32.
26. Mendez-Ferrer S, Lucas D, Battista M and Frenette PS: Haematopoietic stem cell release is regulated by circadian oscillations. Nature 2008; 452: 442-7.
27. Scheiermann C, Kunisaki Y and Frenette PS: Circadian control of the immune system. nature reviews. Immunology 2013; 13: 190-8.
28. Singh R, Sharma PK and Malviya R: Review on chronopharmaceutices - a new remedy in the treatment of various diseases. Euro J Biological Sci 2010; 2(3): 67-76.
29. Patel B, Prajapati P and Patel C: Chronopharmacolgy and chronopharmaceutical of cardiovascular disease. Res J Pharma Bio Chem Sci 2011; 2(2): 740-483.
30. Martin RJ and Banks-Schlegel S: Chronobiology of asthma. Am J Respir Crit Care Med 1998; 158: 1002-07.
31. Hori K, Zhang QH, Li HC, Saito S and Sato Y: Timing of cancer chemotherapy based on circadian variations in tumor tissue blood flow. Int J Cancer 1996; 65: 360-64.
32. Levi V: Circadian chronotherapy for human cancers. Lancet Oncol 2001; 2: 307-15.
33. Humphries TJ, Root JK and Hufnagel K: Successful drug specific chronotherapy with the H2 blocker famotidine in the symptomatic relief of gastro-esophageal reflux disease. Ann New York Acad Sci 1991; 517-18.
34. Cincotta AH and Meier AH: Circadian rhythms of lipogenic and hypoglycaemic responses to insulin in the golden hamster. J Endocrinol 1984; 103: 141-46.
35. Satyanarayana V and Krishnan P: Chronopharmacology: tailoring therapy to endogenous rhythms. Journal of International Medicine and Dentistry 2015; 2 (1): 03-16.
36. Menet JS, Rodriguez J, Abruzzi KC and Rosbash M: Nascent-Seq reveals novel features of mouse circadian transcriptional regulation. eLife 2012; 1:e00011.
37. Koppiseti VS and Sunalatha SH: Chronopharmacologly and chronopharmacotherapy-a guide to better health. Res J Pharma Bio and Chem Sci 2011; 2: 266-28.
38. Sharma D and Malhotra, P: Chronopharmacology and drug prescribing pattern of physicians in a tertiary care hospital of North India. International Journal of Basic & Clinical Pharmacology 2018; 7(3), 499-502.
39. Lago A, Geffner D, Tembl J, Landete L, Valero C and Baquero M: Circadian variation in acute ischemic stroke: a hospital-based study. Stroke; A Journal of Cerebral Circulation 1998; 29: 1873-5.
40. David SHG: Pharmacology of cardiovascular chrono-therapeutics agents. AJH 2001; 14: 296-01.
41. Lee YC, Wang HP, Lin LY, Chuang KJ, Chiu HM and Wu MS: Circadian change of cardiac autonomic function in correlation with intra-esophageal pH. J Gastroenterol Hepatol 2006; 21: 1302-8.
42. Konturek PC, Brzozowski T and Konturek SJ: Gut clock: Implication of circadian rhythms in the gastrointestinal tract. J Physiol Pharmacol 2011; 62: 139-50.
43. Hershcovici T, Jha LK, Cui H, Powers J and Fass R: Night-time intra-oesophageal bile and acid: A comparison between gastrooesophageal reflux disease patients who failed and those who were treated successfully with a proton pump inhibitor. Ali Pharma Ther 2011; 33: 837-44.
44. Baraldo M: The influence of circadian rhythms on the kinetics of drugs in humans. Expert Opin Drug Metab Toxicol 2008; 4: 175-92.
45. Fischer TW, Greif C, Fluhr JW, Wigger-Alberti W and Elsner P: Percutaneous penetration of topically applied melatonin in a cream and an alcoholic solution. Skin Pharmacol Physiol 2004; 17: 190-4.
46. Konturek PC, Brzozowski T and Konturek SJ: Gut clock: implication of circadian rhythms in the gastrointestinal tract. J Physiol Pharmacol 2011; 62: 139-50.
47. Labrecque G and Bélanger PM: Biological rhythms in the absorption, distribution, metabolism and excretion of drugs. Pharmacol Ther 1991; 52: 95-07.
48. Anderson NH, Devlin AM, Graham D, Morton JJ, Hamilton CA and Reid JL: Telemetry for cardiovascular monitoring in a pharmacological study: new approaches to data analysis. Hypertension 1999; 33: 248-55.
49. Stow LR and Gumz ML: The circadian clock in the kidney. J Am Soc Nephrol 2011; 22: 598-04.
50. Innominato PF, Lévi FA and Bjarnason GA: Chronotherapy and the molecular clock: Clinical implications in oncology. Adv Drug Deliv Rev 2010; 62: 979-01.
51. Touitou Y, Touitou C, Bogdan A, Reinberg A, Auzeby A and Beck H: Differences between young and elderly subjects in seasonal and circadian variations of total plasma proteins and blood volume as reflected by hemoglobin, hematocrit and erythrocyte counts. Clin Chem 1986; 32: 801-4.
52. Stow LR and Gumz ML: The circadian clock in the kidney. J Am Soc Nephrol 2011; 22: 598-04.
53. Innominato PF, Lévi FA and Bjarnason GA: Chronotherapy and the molecular clock: Clinical implications in oncology. Adv Drug Deliv Rev 2010; 62: 979-01.
54. Ando H, Yanagihara H, Sugimoto K, Hayashi Y, Tsuruoka S and Takamura T: Daily rhythms of P-glycoprotein expression in mice. Chronobiol Int 2005; 22: 655-65.
55. Murakami Y, Higashi Y, Matsunaga N, Koyanagi S and Ohdo S: Circadian clock- controlled intestinal expression of the multidrug-resistance gene mdr1a in mice. Gastroenterology 2008; 135: 1636-44.
56. Ohdo S: Changes in toxicity and effectiveness with timing of drug administration: Implications for drug safety. Drug Saf 2003; 26: 999-010.
57. Smolensky MH: Circadian rhythms in medicine. CNS Spectra 2001; 6: 467-74, 479-82.
58. Alvarez D, de las Heras M, Abecasis R, Terg R, Gerona S and Albornoz L: Daily variation in portal blood flow and the effect of propranolol administration in a randomized study of patients with cirrhosis. Hepato 1997; 25: 548-50.
59. Xu C, Li CY and Kong AN: Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharm Res 2005; 28: 249-68.
60. Homolya L, Váradi A and Sarkadi B: Multidrug resistance associated proteins: export pumps for conjugates with glutathione, glucuronate or sulfate. Bio 2003; 17: 103-14.
61. König J, Nies AT, Cui Y and Keppler D: Conjugate export pumps of the multidrug resistance protein (MRP) family: Localization, substrate specificity and MRP2-mediated drug resistance. Bioc Biophys Acta 1999; 1461: 377-94.
62. Bass J and Takahashi JS: Circadian integration of metabolism and energetics. Science 2010; 33: 1349-54.
63. Bellet MM and Sassone-Corsi P: Mammalian circadian clock and metabolism - the epigenetic link. J Cell Sci 2010; 123: 3837-48.
64. Hoffman DA, Wallace SM and Verbeeck RK: Circadian rhythm of serum sulfate levels in man and acetaminophen pharmacokinetics. Eur J Clin Pharmacol 1990; 39: 143-8.
65. Lo Sasso G, Petruzzelli M and Moschetta A: A translational view on the biliary lipid secretory network. Biochim Biophys Acta 2008; 1781: 79-96.
66. Pöyhönen MJ, Uusitalo UM, Kari A, Takala JA, Alakuijala LA and Eloranta TO: Urinary excretion of polyamines: Importance of circadian rhythm, age, sex, menstrual cycle, weight and creatinine excretion. Am J Clin Nutr 1990; 52: 746-51.
67. Rao VV, Rambhau D, Rao BR and Srinivasu P: Circadian variation in urinary excretion of ciprofloxacin after a single-dose oral administration at 1000 and 2200 hours in human subjects. Antimicrob Agents Chemother 1997; 41: 1802-4.
68. Ghiciuc CM, Cozma-Dima CL, Pasquali V, Renzi P, Simeoni S and Lupusoru CE: Awakening responses and diurnal fluctuations of salivary cortisol, DHEA-S and a-amylase in healthy male subjects. Neuro Endocrinol Lett 2011; 32: 475-80.
69. Rajkumar LA and Kumar SV: Evaluation of chronosensitivity and Chronopharmacology of some centrally acting potential drugs in albino Wistar rats. Scholars Research Library 2010; 1(4): 52-56
70. Martin RJ and Banks-Schlegel S: Chronobiology of asthma, Am J Respir Crit Care Med. 1998; 158: 1002- 07.
71. Muller JE, Tofler GH and Stone PH: Circadian variation and triggers of onset of acute cardiovascular disease. Circulation 1989; 79: 733-43.
72. Singh S, Singh S, Singh Y, Gupta D, Saxena P, Gupta S, Singh A and Srivastva A: Chronopharmacology: recent advancements in the treatment of diabetes mellitus through chronotherapy. International Journal of Pharmacy and Pharmaceutical Sciences 2017; 9: 87-99.
    

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    How to cite this article:

    Kapadia S, Kanase V, Kadam S, Gupta P and Yadav V: Chronopharmacology: the biological clock. Int J Pharm Sci & Res 2020; 11(5): 2018-26. doi: 10.13040/IJPSR.0975-8232.11(5).2018-26.

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