This document discusses xenobiotics, biotransformation, and drug metabolism. It defines xenobiotics as chemicals foreign to the body, like pollutants and drugs, that enter through inhalation. Biotransformation involves the liver converting drugs into more water-soluble metabolites through Phase I and Phase II reactions to allow for excretion. Phase I involves oxidation, reduction, and hydrolysis. Phase II conjugates metabolites with compounds like glucuronic acid, sulfate, acetyl groups, or glutathione to further increase water solubility for renal or biliary excretion. The major site of biotransformation is the liver, which terminates drug action and facilitates removal from the body.

1. Dr. Haji Bahadar
Assistant Professor, KMU-IPMS

2. Introduction
 What are xenobiotics?
We inhale air containg hydrocorbons chemicals (both
good and bad), and drugs (both good and bad). These
substances are called xenobiotics. Examples;
Environmental pollutants, Agrochemicals etc.
 Once inside the body, they are transported to the liver,
where enzymes start the process of breaking them down
and finally disposed of.
 Def;:a chemical compound (as a drug, pesticide, or carcinogen) that is
foreign to a living organism.

3. Definition of biotransformation
 Biotransformation: Chemical alteration of a drug,
within the body.
 Biotransformation is the conversion of drug molecules to
more water-soluble metabolites.
General outcomes of biotransformation are
 Drug Inactive metabolite(s) Paracetamol
 Drug Active metabolite(s)
Diazepam converts to Desmethyl diazepam
Allopurinol converts to Alloxanthine
 Prodrug Drug

4. Prodrug???
A prodrug means a compound that, after
administration, is metabolized (i.e., converted within
the body) into a pharmacologically active drug.
Example: Levodopa is converted to the active dopamine
by DOPA decarboxylase
Enalapril is bioactivated by esterase to the active
enalaprilat

5. The sites of biotransformation
 Predominantly, the liver

6.  Biotransformation is a major mechanism for drug
elimination from the body
 During metabolism metabolites that are more polar
than the parent drug are produced.
 Metabolism usually terminates the pharmacologic
action of the parent drug .
Note:
The kidneys cannot efficiently excrete highly fat-
soluble drugs that readily cross cell membranes
because they are reabsorbed in the last stages of
filtration. These compounds must first be
metabolized in the liver to more water-soluble
compounds and then removed.

7. Biotransformation Classification
 There are two broad types of biotransformation, called
phase I and phase II reactions.
1. Phase I reactions: In phase I reactions
modification of the drug molecule occurs via
oxidation, reduction, or hydrolysis.
Oxidation: addition of oxygen or removal of
hydrogen.
RNH2 O RNHOH

8.  Hydrolysis: Chemical reaction of a compound
with water .
 Ester + water Esterases Alcohol & Acid
 Reduction: addition of hydrogen or removal of
oxygen .
 A.NITRO Reduction- RNo2 RNH2

9. Phase II reactions
 In phase II reactions, there is conjugation of metabolites
with endogenous compounds in order to increase the water
solubility of metabolites.
Types:
1. Glucuronidation: reaction of drug molecules with
Glucuronic acid. Enzyme involved: glucuronyl
transferase (bilirubin, androgens, estrogens,
mineralocorticoids, glucocorticoids, morphine and
chloramphenicol)
2. Sulfation: Conjugation of a sulfo group. Example:
Sulfation of minoxidil
Enzyme: sulfotransferase

10. 3. Acetylation: Acetylation is the process where an
acetyl functional group is transferred (Isoniazid)
4. Methylation: methylation is the process where a
methyl functional group is transferred. Enzyme
involved: methyl transferase .
5. Glutathione (GSH) conjugation: conjugation with
glutathione. Enzyme involved is Glutathione S-
transfrerases.
Glutathione is a highly important antioxidant in the
human body.

11. Paracetamol metabolism

12. Advantages of biotransformation
 Termination of drug action - (↓ Toxicity)
 Reduced lipophilicity.
 Renal / biliary excretion ↑ - (↓Renal
reabsorption)

13. ELIMINATION
 Removal of the drug from the body is called
elimination. The major modes of drug elimination are:
● Biotransformation to inactive metabolites
● Excretion via the kidney