absorption, distribution, metabolism and elimination: part ii joseph graziano, ph.d
TRANSCRIPT
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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.Oxidationa. 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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