About Drug metabolism: Chemoinformatics

2.  Drug metabolism is a biochemical modification
of pharmaceutical substances by living
organisms usually through specialized enzymatic
activity.

3. Drug Metabolism does-
metabolism of drugs into more hydrophilic
metabolites
Generates more polar (water soluble), inactive
metabolites.

4. Site of Biotransformation
Rough Endoplasmic Reticulum and cytosol
Enzymes concentratedly localized in Hepatocytes in
Liver.
Other organs with significant metabolic capacity are
GI tract, kidneys and lungs.

5. Stages of drug metabolism
 Absorption
 Distribution
 Metabolism
 Elimination

6. Metabolism
Phase I – functionalization reactions
Phase II – conjugation reactions

7. Phase I Metabolism
(Includes:oxidation,reduction,hydrolysis,
hydration and isomerization )
 Cytochrome P450
 Converts the parent drug to a more polar
metabolites

8. Cytochrome P450 Nomencleature
 17 families (CYPs) –
sequences > 40% identical (identified by numeric
number)
CYP1, CYP2
 further into subfamilies –
sequences >55% identical (identified by a letter)
CYP1A, CYP2D
 different isoforms – (identified by another numeric
number)
CYP2D6, CYP3A4

9.  Occurs mostly in cytosol.
 Covalent bonding is formed between a functional
group metabolite and an endogenous substrate.
 Highly polar – rapidly excreted in urine.
 Usually inactive
except : morphine 6-glucuronide
Phase II (conjugation reactions)
True detoxification of drugs

10. Factors affecting Drug Metabolism
Environmental Factors:
Induction
Inhibition
Disease Factors
Age and Sex
Genetic Variation

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