Absorption, Distribution, Metabolism and Elimination: Part II

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Absorption, Distribution, Metabolism and
Elimination Part II

• Joseph Graziano, Ph.D.

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Aspirin Metabolism
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Organs Involved in Drug Biotransformation

• Liver
• Gastrointestinal mucosa
• Lung
• Skin
• Placenta

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1.Oxidation a. Aromatic hydroxylation
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b. Aliphatic hydroxylation
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d. Oxidative O-dealkylation
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e. S-oxidation
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4. Conjugationa. Glycine
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b. Glucuronic acid
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d. Acetylation
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Examples of Characteristic Inducers of the Major
P450 Gene Families

• CYP 1A2
• CYP 2C19
• CYP 2C9
• CYP 2D6
• CYP 2E1
• CYP 3A4, 5, 7

• Tobacco
• Prednisone
• Rifampin
• Dexamethasone?
• Ethanol
• Barbiturates

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Examples of Inhibitors of the Major P450 Gene
Families

• CYP 1A2
• CYP 2C19
• CYP 2C9
• CYP 2D6
• CYP 2E1
• CYP 3A4, 5, 7

• Cimetidine
• Ketoconazole
• Isoniazid
• Cimetidine
• Water Cress
• Cimetidine, grapefruit juice

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Erythromycin (an antibiotic) and Verapamil ( a
calcium channel blocker) are also important
inhibitors of P-450
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