Drug Disposition Overview - Pharmacology and at UCSD
Drug Disposition Overview - Pharmacology and at UCSD
Drug Disposition Overview - Pharmacology and at UCSD
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BIOM/PHAR 255 Winter 2013 Halpert - Jan. 17, 2013<br />
Consequences of genetically impaired<br />
metabolism (similar to chemical inhibition)<br />
•When drug is inactiv<strong>at</strong>ed by<br />
metabolism: Higher blood levels<br />
= increased therapeutic effect<br />
<strong>and</strong> risk for side effects.<br />
•When drug is activ<strong>at</strong>ed by<br />
metabolism: Higher blood levels<br />
of unchanged prodrug <strong>and</strong> lower<br />
levels of active metabolite =<br />
decreased therapeutic effect.<br />
Single dose<br />
Poor metabolizer<br />
(PM)<br />
Time<br />
Mult iple dosage<br />
PM, t 1 / 2 = 2 4 h<br />
Cm ean = 2 8 m / L<br />
EM, t1/ 2 = 6 h<br />
C mean = 7 .5<br />
mg/ L<br />
Time<br />
Extensive<br />
m e t aboliz e r<br />
(EM)<br />
Molecular Mechanisms th<strong>at</strong> Alter CYP Function<br />
Log (plasma conc.)<br />
TiPS, 20: 342, 1999<br />
14 of 22<br />
Gene Dosage Effect (similar to induction)<br />
Nortriptyline<br />
antidepressant<br />
CYP2D6 genes<br />
Major P450 Alleles<br />
10-hydroxynortriptyline<br />
TiPS, 20: 342, 1999<br />
TiPS, 20: 342, 1999
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