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ANANBIOANAL - 2010
Pharmaceutical R & D Summit
doi:10.4172/2155-9872.1000006
Role of Drug Metabolism and Pharmacokinetic Studies in Drug
Discovery and Development
Chandra Prakash
Senior Director, Dept. of Drug Metabolism and Pharmacokinetics Biogen Idec, Cambridge, USA
T
he drug development process is scientifically complex, time consuming and
expansive. Recent data indicate that the discovery and development of a
new drug costs around 1.0 billion dollars and takes 12-15 years for the drug to
reach the marketplace. In addition, 90% of all drugs in clinical development fail to
make to the market. Efforts are being made to reduce attrition of drug candidates
during the various stages of drug discovery and development, and to bring safer
drugs to the market. The major reasons for the attrition and serious side effects
are sub-optimal drug metabolism and pharmacokinetic (DMPK) profile, poor clinical
efficacy and the formation of reactive metabolites. Given the inherent inefficiency
of the development, it is essential to optimize/minimize such factors early in drug
discovery process. This has led to greater integration of DMPK functions into early
stages of drug discovery process and in addition to potency and selectivity; drug
candidates are selected on the basis of DMPK properties, e.g. low clearance,
good oral bioavailability, optimum half-life, and an acceptable metabolism profile in
preclinical species and humans. This presentation will summarize the in vivo/in vitro
techniques used for rapid determination of the DMPK profiles including absorption,
metabolic stability, metabolite structures, cytochrome P450 inhibition/induction, and
pharmacokinetics and role of these studies in the selection of the drug candidates
for further development. Knowledge of metabolic profiles of these candidates in
an early stage of drug discovery is essential to select compounds with favorable
pharmacokinetic credentials and to aid medicinal chemists for rational drug design.
ANALBIOANAL-2010
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