Drug Disposition Overview - Pharmacology and at UCSD

BIOM/PHAR 255 Winter 2013 Halpert - Jan. 17, 2013
Importance and General Principles
of Drug Metabolism
Drug Therapy: The challenges
1. Non-responders
Only 30-60 % of patients respond to the
common drugs.
2. Serious adverse drug reactions (ADRs):
5-7 % of all hospital admissions
2 days prolonged hospital visit
$2,500 per patient, $100 billion in USA per year
100,000 deaths annually in US
2 of 22
Drug Metabolism in Clinical
Practice
• Goals
– Understand factors that
affect metabolism of a
drug
– Predict metabolism of
the drug in an individual
– Design rational therapy
regimen that is safe and
effective.
• Need to know
– Which enzymes
(isoforms) metabolize
the drug
– How each enzyme is
affected by genetic
and environmental
factors (including other
drugs)
– The relative
therapeutic efficacies
and toxicities of drug
and metabolites
Reasons for termination of drug candidates in
development in 2000
Attrition due to PK/bioavailability decreased from 40% to 8% between 1991 and
2000 in large measure due to incorporation of these concepts in early drug
discovery. Guengerich, F.P. (2007). Chem Res.
Toxicol. 20:344-369.