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THE PHARMA REVIEW (MARCH - APRIL 2013)

Chronopharmacokinetic Studies - A Tool to Optimize Dosage Regimen and Reduce Adverse Effects

Jagtar Singh1, Yash Paul1 & Bhupinder Singh2

Introduction: Conventional strategies of designing drug delivery systems have been based on homeostatic theory i.e. the assumption that biological physiology is constant over time. But existence of circadian rhythm for almost all body functions viz. heart rate, blood pressure, body temperature; hormonal concentrations, gastric secretions, renal functions, etc. have been supported by Chronobiological studies. The findings of these studies have lead to the origin of a novel concept - Chronopharmacokinetics that correlates temporal changes in drug absorption, distribution, metabolism and excretion with the moment of its administration. Recently introducing the time of administration as a variant in pharmacokinetic research has become increasingly common. Studies have established that in general drugs show higher bioavailability when administered in the morning than when taken in the evening. On the other hand physiological functions and pathological states, which owe circadian rhythm, are also suggestive of Chronopharmacotherapy in which drug dosing regimen is synchronized with the biological rhythms for enhancing therapeutic efficacy and reducing the incidences of adverse effects. The available findings of different studies conducted by different groups, with gentamicin, tobramycin, amikacin, ceftriaxone, ciprofloxacin, propranolol, oxprenolol, nifedipine, verapamil, sumatriptan, ketoprofen, Indomethacin etc. revealed daily variations in the drugs' kinetics and are suggestive of the dose-response relationship which is always dependent on the time of day at which dose is administered. Thus drug Chronopharmacokinetic knowledge is clinically relevant and is an important consideration during drug therapy.

 

 

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