54 teja krishna 23.09.2010

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    CHRONO

    PHARMACOKINETICSUnder the guidance ofProf. T.E.GOPALA KRISHNA MURTHY. M.Pharm .,Ph.D

    Dept. Of Pharmaceutics

    By

    M. Teja Krishna

    07101R0054

    Bapatla College of Pharmacy

    23.09.2010

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    DEFINITION

    Chrono pharmacokinetics deals with the study

    of temporal changes in

    Distribution

    Absorption

    Metabolism

    Elimination

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    RELATED TERMS

    Chronokinetics of drug:

    Rhythmic chang s in its harmac inetics.

    Chronethesy :

    Changes in the s scepti ility r sensitivity f a targetsystem.

    Chrono biology:

    Science that studies the bi l gical rhythms.

    Chronotherapeutics:

    Applicati n of chronobiological principle to the treatment

    ofdiseases.

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    BODY RHYTHMS

    NATURE OF

    RHYTHMDURATION EXAMPLE

    Ultradian rhythms

    Shorter than day with a length

    from thousands of the second

    ( like impulse in the neuron) to

    the rhythm of about 0 min one

    sleeping cycle

    Impulse in neuron, from

    REM sleep to deep sleep.

    Circadian rhythmsWhich lasts about one day

    Sleep walking rhythm, the

    body temperature

    Infradian rhythmsLonger than day

    Menstrual cycle, yearly

    rhythm, bird migration.

    4

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    NEED FOR CHRONOKINETIC STUDY

    If Pharmacodynamics & Pharmacokinetics parameters on

    depend biological rhythms.

    When the symptoms of disease are clearly circadian rhythms. When ever the incidence of adverse effects is influenced by the

    circadian rhythms.

    If the maximum therapeutic efficiency is dependent up on

    circadian rhythms.

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    EFFECT ON LIVING ORGANISMS

    Circadian rhythms are endogenously generated

    in various species.

    Dr s ili m l st r

    N r s r

    Mouse

    Golden hamster

    6

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    INFLUENCE ON BIOCHEMICAL &

    PHYSIOLOGICAL CHANGES

    Sleep activity cycle (10: 0 pm 6: 0 am)

    Basal gastric acid secretion, WBC count are peak at latenight.

    Serum cholesterol & triglycerides concentration are highest

    early in the evening. Haemoglobin & Insulin levels are greatest in the afternoon.

    Intra ocular pressure is highest in between pm & 4 pm andlowest in the evening.

    B.P increases in the morning after night sleep; peaks in the

    afternoon and early in the evening; slowly decreasesreaching minimum during time sleep.

    Membrane nerve cell permeability to ions- the cell K+ conc.and K+ efflux from cells is low around pm.

    7

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    ON A.D.M.E PARAMETERS

    ABSORPTION:

    Gastric acid secretion & PH.

    Gastric motility Gastric emptying time.

    Gastro intestinal blood flow

    8

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    DISTRIBUTION:

    Body size and composition.

    Blood flow to various organs. Drug protein binding.

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    METABOLISM:

    Liver enzyme activity.

    Hepatic blood flow.

    10

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    EXCRETION:

    Glomerular filtration

    Renal blood flow. Urinary PH.

    Tubular reabsorption.

    11

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    CIRCADIAN TIME STRUCTURE

    1

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    CHRONOKINETIC BASED THERAPY

    Ami lyc si s:Peak renal toxicity when injected in the middle of the rest period.

    Renal toxicity is reduced by giving drug as single daily injection atday time.

    Cef trixime:Total clearance maximum during the activity period and minimum atrest period.

    Ci r f l x c i :Amount eliminated in urine was greater when the drug was

    administered at 10:00 hr than when it is given at :00 hr.

    Am icilli :Biliary & renal clearance were significantly higher during the active

    cycle of rats than during the sleep cycle.

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    Benzodi zepines:

    The elimination of half life of Midazolam was found to be

    shortest at 14:00 hr and its longest at :00 hr.

    Ket mine, Propofol nd H logenated agents:Action longer during the night than during the day.

    Halot ane:

    Greatest efficiency of Halothane occurred between 4:00

    and 06:00 hr

    15

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    DrugHour administration to achieve maximum

    theraphy

    NSAIDS:

    Ketoprofen

    Indomethicin

    Morning

    Anti-migrane drugs:

    SumatriptanMorning

    Immunosuppresants:

    Cyclosporin

    Resting period

    Opiod analgesics:

    Tramadol Evening

    Anti-Cancer drugs:

    5-Fluro Uracil

    Cisplatin

    Anthracyclins

    Etopside

    nd part of night

    15:00 to 18:00

    Early morning

    End of night 16

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    CONCLUSION

    Selection and dosage timing of medication.

    Right time of dose for the right person.

    Maximum drug availability at peak hours. Optimisation.

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    REFERENCE

    S Nayak.U.Y, Shavi.G.V, Nayak.Y, Averinen.R.K, Mutalik.S, Reddy.S.M,

    Chronotherapeutic drug delivery in blood pressure .A programable drug

    delivery system, Journal of control release Jun 00 ; 1 6( ):1 5( )

    Smolensky, Micheal H , Peppas, Nicholas a ,Chronobiology, drug delivery

    and Chronotherapeutics ,Advanced drug delivery review, Aug 007;5 ( -10);8 8-851

    Roy. Pallab ,Shahiwala. Aliasgar, Multiparticulate formulation approach to

    pulsalite drug delivery ; Current perspectives , Journal of control release ;

    official Journal of release society ,Mar 00 ; 1 4( ) ;74-80

    ajrcem.ats journals.org, Indian pharmacopoeia 1 6, Ministry of Health and Family Welfare, The

    Controller Of Publications, New Delhi, 1 6, 67

    18

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    1

    THANK

    YOU