(log ppb) HPRT VF (x 10
(log ppb) HPRT VF (x 10
(log ppb) HPRT VF (x 10
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Drug-Drug Metabolism Interaction<br />
• Drugs are primarily detoxified by enzymatic reactions; enzymes<br />
therefore control the rate of their metabolism<br />
• There are thousands of drugs, but only dozens of enzymes – so<br />
there will be a great deal of substrate overlap<br />
• Example: Ketoconazole (common antifungal) inhibits hydroxylation<br />
activity of CYP3A4, thereby prolonging action of dozens of other<br />
3A4 ligands (APAP, diazepam, warfarin, steroids, verapimil),<br />
• Example: Flavones in grapefruit juice induce CYP3A4, shortening<br />
these drugs’ actions<br />
• Example: Phenobarbital and rifampin induce CYP3A4 and therefore<br />
ethinylestradiol metabolism; causing a decrease in its contraceptive<br />
effect
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