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 />
Conversion of a Hydrophobic <strong>Drug</strong> to a<br />
W<strong>at</strong>er-Soluble Metabolite<br />
Phenytoin<br />
O<br />
H<br />
N<br />
NH<br />
O<br />
CYP<br />
HO<br />
4-Hydroxy<br />
phenytoin<br />
O<br />
W<strong>at</strong>er solubility<br />
H<br />
N<br />
NH<br />
O<br />
UGT<br />
COOH<br />
O<br />
O<br />
HO OH<br />
General P<strong>at</strong>hways of <strong>Drug</strong> Metabolism<br />
REACTION ENZYME<br />
Hydrolysis<br />
Reduction<br />
Oxid<strong>at</strong>ion<br />
Esterase, peptidase, epoxide hydrolase<br />
Azo <strong>and</strong> nitro reduction<br />
Carbonyl, disulfide, sulfoxide, quinone<br />
Alchohol <strong>and</strong> aldehyde dehydrogenase<br />
Xanthine <strong>and</strong> diamine oxidase<br />
Monomine oxidase<br />
Prostagl<strong>and</strong>in H synthase<br />
Flavin-monooxygenases<br />
Cytochrome P450s<br />
Conjug<strong>at</strong>ion Glucuronide, sulf<strong>at</strong>e, glut<strong>at</strong>hione, acyl<strong>at</strong>ion,<br />
methyl<strong>at</strong>ion<br />
4-Hydroxy-phenytoin<br />
Β-D-glucuronide<br />
OH<br />
O<br />
H<br />
N<br />
Expose or<br />
Introduce.<br />
-OH<br />
-NH 2<br />
-SH<br />
-COOH<br />
NH<br />
Synthetic<br />
O<br />
4 of 22<br />
Phase I:<br />
Purpose of phase I <strong>and</strong> phase II<br />
metabolism<br />
Detoxify<br />
Enhance excretion<br />
RH --> ROH (more w<strong>at</strong>er<br />
soluble <strong>and</strong> prepares for<br />
phase II)<br />
Phase II = Conjug<strong>at</strong>ion:<br />
Enhance excretion<br />
Detoxify (e.g. GSH)<br />
Acts on parent drug<br />
Acts on phase I<br />
metabolite<br />
Cytochrome<br />
P450<br />
Cytochromes P450<br />
Excretion<br />
Xenobiotic<br />
Phase I<br />
Metabolism<br />
Excretion<br />
Phase II<br />
Metabolism<br />
Glucuronides<br />
Sulf<strong>at</strong>es<br />
GSH-conjug<strong>at</strong>es<br />
Other conjug<strong>at</strong>es<br />
Excretion
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