Pharmacokinetics and Biodistribution Studies of Selected Racemic Drugs

Abstract

Regulatory considerations and aspect of chirality started in the early 1990s Regulatory agencies require clinical efficacy and safety data of each enantiomeric form before giving approval Latest data reveal that 75percentage of drugs approved after the year 2000 are pure enantiomers It is well known that asymmetry plays an important role in most of the biological processes As the physiological environment is chiral therefore enantiomeric molecules are expected to differ in their pharmacokinetic profile and pharmacological behavior However to study such separation of enantiomers is very important Chiral separation of enantiomers helps in understanding the pharmacological profiles of racemates and enantiomers There is an increase in the demand of chiral separation methods in industries as racemates are being replaced by single enantiomeric forms The method development for enantiomeric separation is challenging and time consuming Chiral separation and analysis enhances the clarity of the pharmacological and toxicological data obtained and can also help in controlling the quality of synthesized drugs This thesis deals with the enantiomeric separation and stereospecific disposition of two important pharmaceutical drugs with respect to their pharmacokinetics and biodistribution The first drug ketorolac is a nonselective COX inhibitor in the family of heterocyclic acetic acid derivatives Ketorolac is an isostere of ketoprofen The second drug chosen was venlafaxine which is an antidepressant of SNRI category Both drugs are available as racemates and are important and widely used The objective of the present study was to understand the pharmacokinetics and biodistribution behavior of above drugs after developing simple reliable rapid and sensitive analytical and bioanalytical methods As venlafaxine is converted to Odesmethylvenlafaxine in system therefore it is also studied along with venlafaxine.