This document discusses drug metabolism and phase I reactions. It defines drug metabolism as enzymatic chemical reactions that convert drugs into metabolites within the body. Drug metabolism is divided into two phases: phase I and phase II reactions. Phase I reactions introduce or expose functional groups through oxidation, reduction, and hydrolysis, making the drug more polar and susceptible to phase II reactions. Some examples of phase I reactions discussed are aromatic hydroxylation, oxidation of olefins, benzylic carbons, carbon atoms next to carbonyl groups, and aliphatic carbons. Reduction and hydrolytic reactions during phase I are also summarized.

1. PART II
Dr. P. PARTHIBAN
Professor
Vellalar College of Pharmacy

2. Points to be discussed
 Definition
 Phase –I reactions

3. Drug metabolism is defined as
 Enzymatic chemical reactions that are responsible
for the conversion of drugs into metabolites with in
body.
(OR)
 The biochemical modification of one chemical
form to another, occurring usually through
specialized enzymatic systems.

4.  Drug metabolism has been divided into two
categories
Phase I (Funtionalization Reaction)
Phase II (Conjugation reaction)
Phase I
 They are enzyme biotransformation reaction, in which
drug may undergo a wide varity of oxidation,
reduction and hydrolysis resulting in introduction or
unmasking of functional group
↓ which is
↑ce the polarity of the molecule and serve as a centre
for the second phase of metabolic reaction. It is called
as funtionalization reaction.

5.  These biotransformations are also called as
synthetic reaction, opposite to synthetic phase II
reactions.
 Functional groups -OH (Hydroxyl), -SH (Thiol),
-COOH (Carboxyl), -NH2 (Amino) are called as
xenobiotics
↓ to yield
a more water soluble chemical entity.

6. PHASE - I

7. I. OXIDATIVE REACTION
(LOSS OF ELECTRON FROM A SUBSTANCE IN A REACTION)
 Oxidation is a common reaction in xenobiotic.
 Oxidation reaction increases the hydrophilic of the xenobiotics by
introducing the polar functional group (OH).
 The reaction catalysed by a group of membrane BOUND MONO
OXYGENASE (Cytochrome 450)
 The enzyme require both molecular OXYGEN (O2) & the reducing agent
NADPH to effect reaction.
RH + O2 + NADPH + H+→ ROH + H2O + NADP+

8. OXIDATION OF AROMATIC CARBON ATOM
 Aromatic hydroxylation refers to mixed function
oxidation of aromatic compounds to their
corresponding phenols.
 The reaction proceeds via formation of reactive
intermediate Arene oxide or Arene epoxide, which
results in multiple reactions.
NHCOCH3 NHCOCH3
OHAcetanilide
R
R
OH
R R
o
Arene oxide

9. Oxidation of Olefines
Oxidation of non aromatic C-C double bond is analogue to
aromatic hydroxylation; it proceeds via epoxide to yield 1,2
dihydrodiol. The epoxide is not very reactive like aromatic
epoxide

10. Oxidation of Benzylic carbon
 Carbon atom attached directly to the aromatic ring (Benzylic
carbon) is hydroxylated to corresponding carbinols or alcoholic
metabolite. Primary alcohol metabolite is further oxidized to
aldehyde and further to carboxylic acid and secondary carbinol
gets converted to ketone by alcohol and aldehyde
dehydrogenase respectively.

11. Oxidation of Allylic carbon
 Carbon atom adjacent to Olefinic double bonds
undergoes hydroxylation similar to benzylic carbon.

12. Oxidation of carbon atom α to Carbonyl and Imines
 The mixed function oxidase also oxidizes carbon
atom adjacent to carbonyl and imino functionalities

13. Oxidation of
Aliphatic Carbon
Atom
Oxidation of Alicylic carbon
atom
Others oxidation reactions
such as,
 Oxidation involving
C-N system
(Amines reaction)
 Oxidation of carbon-
sulfur system
 Oxidation of Alcohol
and Aldehyde

14. II. Reduction reactions
 Important role in metabolism of many compounds containing
carbonyl, nitro and Azo group.
 Bio-reduction of carbonyl group results in alcohol whereas
nitro and Azo group give rise to amino group.
 The amino and Hydroxyl group are more susceptible to
conjugate.
Reduction of Aldehyde and ketons

15. Reduction of Azo and Nitro compound

16. III. Hydrolytic reactions
Hydrolysis of Esters and Amides
Hydrolysis of Amide

17. Thank you