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BBS2_FT_K4
Objektif Pembelajaran
1. Defenisi biotransformasi
2. Fase I biotransformasi
3. Fase II biotransformasi
4. Enzim yang terlibat
5. Sitokrom P450 dan isoform
6. Faktor genetik dalam biotransformasi obat
Pendahuluan
Xenobiotics- substances foreign to body
Eksresi Metabolisme
(Biotransformasi)
4
Defenisi biotransformasi
L-dopa Dopamine
Inactive Terfenadine is Converted to its Active Metabolite Fexofenadine
activation of prodrug
terfenadine
fexofenadine
Some Xenobiotics Are Metabolized to Carcinogenic Agents
carcinogenesis
• 3,4 Benzopyrene
• Aflatoxin
• N-Acetylaminoflluorene
bioactivation
Bioactivation of acetaminophen; under certain conditions, the electrophile N-acetylbenzoquinoneimine reacts with tissue
macromolecules, causing liver necrosis.
Thalidomide is a Teratogen
– cytochrome P-450
– aldehyde and alcohol dehydrogenase
– deaminases
– esterases
– amidases
– epoxide hydratases
Enzymes catalyzing phase II biotransformation reactions
Consequences
Precipitate toxicity of the object drug. can
be therapeutically beneficial.
Eg:
aversion of alcohol with disulfiram
Valproate
Ketoconazole
Cimetidine
Ciprofloxacin
Erythromycin
INH
Consequences
Drug- drug interactions
Can lead to toxicity. Eg: Alcoholics more
prone to hepatotoxicity of paracetamol due to↑
production of NABQI
Therapeutic benefit. Eg: To treat neonatal
jaundice
Decreased duration of action. Eg: OCP (oral
contraceptive pills) failure
Griseofulvin
Phenytoin, Primidone
Rifampicin
Smoking
Carbamazepine
Phenobarbitone
First Pass Metabolism
Presystemic metabolism/ First pass effect
Metabolism of a drug during its passage from the
site of absorption into the systemic circulation.
↓ed BA
↓ed therapeutic response
SITES
Gut wall
Gut lumen
Liver (major site)
Lungs
Skin
FACTORS AFFECTING BIOAVAILABILITY
100 80 60
60 20
Drug extracted
first-past
• Fraction absorbed is 0.8
• The hepatic extraction ratio : 0.75