chronopharmacokinetics
DESCRIPTION
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IMPLICATIONS OF
CHRONOPHARMACOKINETICS
FOR DRUG DELIVERY
PRESENTED
BYS.SHILPA
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Deals with the study of the temporal changes in the absorption, distribution, metabolism and elimination due to time of administration
CHRONOPHARMACOKINETICS
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WHY STUDY CHRONO- P’KINETICS??
PK- PD VARY WITH TIME
Gastric motility: is double in day time than in night
Plasma protein concentrations are higher in day than in night
Hepatic blood flow has been shown to be greatest at 8 am and Metabolism to be reduced during the night
DRUG TOXICITY CAN BE AVOIDED/ MINIMIZED BY ADMINISTERING AT A PARTICULAR TIME
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CYCLIC VARIATIONS OVER TIME
Ultradian rhythms : <20 hrs
Circadian rhythms : 20-28
Infradian rhythms : >28 hrs Circaseptan : 7 days
Circamensual : 30 days
Circa-annual rhythms : 1 year
BODY RHYTHMS
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CIRCADIAN RHYTHM
“Circa” means around &“diem” means day
Eyes > retina > SCN
SCN passes the information to pineal gland >> melatonin hormone
Exposure of light can change endogenous circadian pace time of light, duration wavelength, intensity, which determine circadian patterns of body
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EXAMPLES OF CIRCADIAN RYTHM WBC count peak at late night
Haemoglobin and insulin are highest in the afternoon
BP increases in morning after night sleep, peaks afternoon & decreases during sleep
SLEEP CYCLE
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CHRONOPHARMACEUTICAL DRUG DELIVERY SYSTEMS
OROS TECHNOLOGY
Osmotic‐controlled Release Oraldelivery System
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CROSS SECTION OF DIFFUCAPS
DIFFUCAPS TECHNOLOGY
CHRONOPHARMACEUTICAL DRUG DELIVERY SYSTEMS
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(A)INTACT UNIT (B)EROSION OF THE TIME DELAY INSERT
PLUGS(C)DRUG RELEASE
EGALET TECHNOLOGY
CHRONOPHARMACEUTICAL DRUG DELIVERY SYSTEMS
• Offers a delayed release
• System consists of an
impermeable shell
With two lag plugs,
active drug is
sandwiched between
the plugs.
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APPLICATIONS
ASTHMA Chronotherapy for asthma is aimed at getting maximal effect from bronchodilator medications during early morning hours.
e.g. Theophylline
GASTROINTESTINAL DISEASES Chronotherapy of peptic ulcers with evening once daily dosing of H2 receptor antagonist.e.g. Ranitidine
ARTHRITIS For osteo arthritis Drug will be given in the noon. For Rheumatoid arthritis Drug will be effective when taken after the evening meale.g. Ibuprofen
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APPLICATIONS
CARDIOVASCULAR DISEASE Diseases such as hypertension, heart attack mostly occurs in the morning.
BP at its lowest during sleep cycle and rises steeply during early morning awakening period. CANCER Cancer drugs administer should be timed to cycles of tumour cells making them more effective against cancer and less toxic to normal tissues.
Blood flow to tumours and tumour growth rate are greater during activity phase than rest phase
By treatment at midnight more tumour cells kill could be achieved with same dose of active cytotoxic therapy.
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CONCLUSION
Importance of biological rhythms in the treatment of diseases
Selection of the appropriate chronopharmaceutical technology should take
into considerations the application range, the ease of manufacturing, the
cost-effectiveness, and the flexibility in the pharmacokinetic profile.
Improve patient outcome and optimize disease management in the future.
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