IMPLICATIONS OFCHRONOPHARMACOKINETICSFOR DRUG DELIVERYS.SHILPA
Deals with the study of thetemporal changes in theabsorption, distribution, metabolism and elimination due totime of administrationCHRONOPHARMACOKINETICS
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 andMetabolism to be reduced during the night DRUG TOXICITY CAN BE AVOIDED/ MINIMIZED BY ADMINISTERINGAT A PARTICULAR TIME
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 endogenouscircadian pace time of light, durationwavelength, intensity, which determine circadianpatterns 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 sleepSLEEP CYCLE
CHRONOPHARMACEUTICAL DRUG DELIVERY SYSTEMSOROS TECHNOLOGYOsmotic‐controlled Release Oraldelivery System
CROSS SECTION OFDIFFUCAPSDIFFUCAPS TECHNOLOGYCHRONOPHARMACEUTICAL DRUG DELIVERY SYSTEMS
(A) INTACT UNIT(B) EROSION OF THE TIME DELAY INSERT PLUGS(C) DRUG RELEASEEGALET TECHNOLOGYCHRONOPHARMACEUTICAL DRUG DELIVERY SYSTEMS• Offers a delayed release• System consists of animpermeable shellWith two lag plugs,active drug issandwiched betweenthe plugs.
APPLICATIONS ASTHMA Chronotherapy for asthma is aimed at getting maximal effect frombronchodilator medications during early morning hours.e.g. Theophylline GASTROINTESTINAL DISEASES Chronotherapy of peptic ulcers with evening once daily dosing of H2 receptorantagonist.e.g. Ranitidine ARTHRITIS For osteo arthritis Drug will be given in the noon. For Rheumatoid arthritis Drug will be effective when taken after theevening 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 morningawakening period. CANCER Cancer drugs administer should be timed to cycles of tumour cells makingthem more effective against cancer and less toxic to normal tissues. Blood flow to tumours and tumour growth rate are greater duringactivity phase than rest phase By treatment at midnight more tumour cells kill could be achieved withsame dose of active cytotoxic therapy.
CONCLUSION Importance of biological rhythms in the treatment of diseases Selection of the appropriate chronopharmaceutical technology should take intoconsiderations 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.