chrono pharmacokinetics

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By: lakshman1021 (2 week(s) ago)

Kindly help in this regard

 

By: lakshman1021 (2 week(s) ago)

Dear Venkateswarlu, I need some information on Chronopharmacokinetics. lakshman1021@gmail.com

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chronopharmacokinetics: 

chronopharmacokinetics Submitted to ANU as a part of 1 st M- Pharm curriculum By I. Venkateswarlu Y10MPH10017 Submitted to G.V. Rami Reddy , M- Pharm ( PhD) Dept of Pharmaceutics A S N Pharmacy college Tenali

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Introduction Need of chronokinetic studies Body rhythms Circadian rhythms of drug pharmacokinetics Drugs undergo chronokinetics Applications Conclusion CONTENTS

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INTRODUCTION CHRONOPHARMACOKINETICS- it involves the study of temporal changes in drug absorption , distribution,metabolism and excretion with respect to time of administration. CHRONOBIOLOGY- science that studies the biological rhythms. CHRONOTHERAPEUTICS- application of chronobiological principles to the treatment of diseases.

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NEED OF CHRONOKINETIC STUDIES Daily variation in pharmacokinetics Narrow therapeutic range Circadian phase dependent diseases

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BODY RHYTHMS- these are the biological process that show cyclic variation over time. TYPES OF BODY RHYTHMS CIRCADIAN RHYTHMS - which lasts for about one day, like sleep-waking rhythm the body temperature ULTRADIAN RHYTHMS - shorter than a day seconds(like heart beat) INFRADIAN RHYTHMS - longer than a day monthly rhythm-menstrual cycle yearly rhythm-bird migration

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CIRCADIAN DEPENDENCE OF DRUG PHARMACOKINETICS ABSORPTION - is altered by circadian changes in gastric empting time gastrointestinal blood flow gastric acid secretion and pH Most lipophilic drugs seems to be absorbed faster when the drug is taken in the morning compared with the evening. Ex: Absorption of valproic acid larger in the morning than in the evening.

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DISTRIBUTION - it is altered by circadian changes in body size and composition blood flow to various organs drug protein binding Peak plasma concentrat ion of plasma proteins like albumin occurs early in the afternoon,while troughs are found during the night. Ex : maximum binding of antineoplastics like cisplatin to plasma proteins is in afternoon and minimum in the morning.

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METABOLISM - it is altered by circadian changes in liver enzyme activity hepatic blood flow For drugs with low extraction ratio depends on liver enzyme activity. For drugs with high extraction ratio depends on hepatic blood flow.

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EXCRETION - is altered by circadian changes in gromerular filtration renal blood flow uninary PH tubular reabsorption All lower during the resting period than in activity period. Ex: acidic drugs like sodium salicylate excreted quickly after evening than morning administration.

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DRUGS THAT UNDERGO CHRONOKINETICS Antibiotics - Aminoglycosides Amikacin General anaesthetics - Benjodiazepines Halothane NSAIDS - Indomethacin Ketoprofen Anticancer drugs - 5-Flurouracil Cisplatin

Circadian rhythms and severity of clinical diseases: 

Circadian rhythms and severity of clinical diseases diseases osteoarthritis Rheumatoid arthritis Peptic ulcer Bronchial asthma Circadian rhythmicity symptoms worse in middle or later of the day Most intense on awakening Symptoms worse in the early (sleep) am Exacerbations more common during sleep

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Time cycle when the diseases show their maximum effect Human circadian time structure

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Application: Asthma: Normal lung functions undergoes circadian changes and reaches a low point in the early morning hours. Chronotherapy for asthma is aimed at getting maximal effect from bronchodilator medications during early morning hours. ex: theophylline preparation taken once a day in the evening →blood level reaches peak

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Gastrointestinal disease: Gastric acid secretion is highest at night. Chronotherapy of peptic ulcers with evening once daily dosing of H2 receptor antagonist (ex: ranitidine) Arthritis: For osteo arthritis→ ibuprofen given in the noon The same drug will be effective when taken after the evening meal for rheumatoid arthritis.

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Cardiovascular disease: Diseases such as hypertension, heartattack and stroke mostly occurs early in the morning. BP at its lowest during sleep cycle and rises steeply during early morning awakening period. Cancer: Chronobiological cycles for normal cells and tumour cells may be different. Cancer drugs administer should be timed to cycles of tumour cells making them more effective against cancer and less toxic to normal tissues.

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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 s phase active cytotoxic therapy.

Conclusion: 

Conclusion the future of kinetic studies of important and dangerous drugs as anticancer agents depend on chronopharmacokinetics since we are hopeful to find a specific time of day in which these agents are more effective and less toxic.

REFERENCES: 

REFERENCES Leon shargel.applied bio-pharmaceutics and pharmacokinetics, 240, 828P. V.Venkateswarulu.bio -pharmaceutics and pharmacokinetics, 306P. C.V.S.Subrahmanyam,Biopharmaceutics and pharmacokinetics, 499-503P.

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Asian journal of pharmaceutics, volume 5, Jan-March 2011. file:///C:/Documents%20and%20Settings/Administrator/Desktop/Chronopharmacokinetic.pdf . www.pubmed.com. www. Sciencedirect . Com .

Q: 

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THANK YOU