54 teja krishna 23.09.2010
TRANSCRIPT
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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.
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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
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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.
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ON A.D.M.E PARAMETERS
ABSORPTION:
Gastric acid secretion & PH.
Gastric motility Gastric emptying time.
Gastro intestinal blood flow
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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.
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EXCRETION:
Glomerular filtration
Renal blood flow. Urinary PH.
Tubular reabsorption.
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CIRCADIAN TIME STRUCTURE
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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
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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
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THANK
YOU