IMPLICATIONS OF

CHRONOPHARMACOKINETICS

FOR DRUG DELIVERY

PRESENTED

BYS.SHILPA

Deals with the study of the temporal changes in the absorption, distribution, metabolism and elimination due to time of administration

CHRONOPHARMACOKINETICS

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

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

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

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

CHRONOPHARMACEUTICAL DRUG DELIVERY SYSTEMS

OROS TECHNOLOGY

Osmotic‐controlled Release Oraldelivery System

CROSS SECTION OF DIFFUCAPS

DIFFUCAPS TECHNOLOGY

CHRONOPHARMACEUTICAL DRUG DELIVERY SYSTEMS

(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.

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

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.

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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THANK YOU