This document discusses biotransformation, or the metabolism, of drugs in the body. It defines biotransformation as the chemical conversion of drugs from one form to another. The major organs involved in drug metabolism are the liver, lungs, kidneys, intestine, and placenta. The enzymes responsible for drug metabolism are divided into microsomal and non-microsomal enzymes. Drug metabolism occurs in two phases - phase I involves processes like oxidation and hydrolysis, while phase II involves conjugation reactions like glucuronidation and sulfation. Factors like the drug's physicochemical properties, genetic factors, age, and diet can influence a drug's metabolism in the body.

1. PRESENTED BY:
Gayatri sati
B.Pharm (VII sem)
D.V.C.P. Lalpur (Rudrapur)

2. Biotransformation
• Biotransformation of drugs is defined as the chemical
conversion of one form to another.
• The term is used synonymously with METABOLISM.
• METABOLISM:
• It is a general term used for chemical transformation of
xenobiotics and endogenous nutrients ( e.g.-Protein,
carbohydrate and fats) within or outside the body.

3. Need for drug biotransformation
XENOBIOTICS:
All chemical substances that are not nutrients for the
body and enter the body though, ingestion, inhalation or
absorption are called as XENOBIOTICs (Greek;
Xeons=foreign) or EXOGENOUS COMPOUNDS.

4. Xenobiotic
Highly
lipophilic
Lipophilic Polar Hydrophilic

5. Functionof biotransformation
Pharmacological inactivation
Toxicological activation/ Bio activation
Pharmacological activation
Active Inactive
Phenytoin P-Hydroxy phenytoin
Amphetamine Phenyl acetone
Activation Reactive intermediates
Isoniazid Tissue acylating intermediate
Paracetamol Imidoquinone of N- hydroxylated metabolite
Inactive(Pro drug) Active
Aspirin Salicylic acid
Phenacetin Paracetamol

6. No change in pharmacological activity
Change in pharmacological activity
Active Active
Digitoxin Digoxin
Diazepam Temazepam
Iproniazid (Antidepressant) Isoniazid (Antituberculer)
Diazepam (Tranquilizer) Oxazepam (Anticonvulsant)

7. Drug metabolizing organs
Decreasing order of drug metabolising ability of various
organs is-
Liver>Lungs>Kidney>Intestine>Placenta>Adrenals>Skin
Brain, Testes, muscles, spleen etc. also metabolise drugs but
to a small extent.

8. Drug Metabolizing enzyme
The enzymes are broadly divided into two categories:-
1) Microsomal enzyme
2) Non-microsomal enzyme
Microsomal enzyme:-
A group of enzymes associated with a certain particulate
fraction of liver homogenate.
These are a mixed function oxidase system or mono-
oygenases.
These requires NADPH and oxygen.
The 2 most impotent microsomal enzyme.
a) NADPH cyctochrome P450 Reductase,
b) Cut.P450

9. Non Microsomal enzyme:
These are present in the cytoplasm and mitochondria of
hepatic cells as well as in other tissues including plasma.
Enzymes occurring in organelles/ sites other than
endoplasmic reticulum are called Non-microsomal enzymes.

10. Phases of biotransformation
Phase I Reaction:-
1) Oxidative reaction
2) Reductive reaction
3) Hydrolytic reaction
Phase II Reaction:-
1) Sulfate conjugation
2) Glucuronide conjugation
3) Glutathione conjugation
4) Amino acid conjugation

11. Oxidation Reactions
 Process of addition of oxygen or removal of hydrogen from a
drug molecule.
Hydroxylation
• Phenytoin Hydroxyphenytoin
Dealkylation
• Codeine Morphine
S-oxidation
• Cimetidine Cimetidine sulfoxide
Deamination
• Amphetamine Benzylmethylketone

12. Reduction reactions
 Addition of hydrogen or removal of oxygen from a drug
molecule.
 Nitro Reduction:
Chloramphenicol arylamine
 Keto Reduction:
Cortisone hydrocortisone

13. Hydrolysis
 Process where a drug molecule is split by the addition of a
molecule of water.
 Both microsomal and non microsomal enzymes maybe
involved.
 E.g.: Acetylcholine+H2O Choline+ acetic acid

14. Phase II reaction
Glucuronide conjugation

15. Glutathione conjugation

16. Sulfate conjugation

17. Factors affecting metabolism of drugs
• Physiochemical properties of the drug
Molecular size
pKạ acid/base characteristics
Lipophilicity
Steric characteristics
• Chemical factor
Enzyme induction
Enzyme inhibition

18. • Biological factor
Species difference
Genetic differences
Sex differences
Age differences
Diet

19. References
1. Brahmankar D.M,Jaiswal Sunil; Biopharmaceutics and
pharmacokinetics-A treatise, third edition
2017(reprint),published by vallabh prakashan Delhi page
no.140-194.
2. Kulkarni S.K., Pawar, shedbalkar; Biopharmaceutics and
pharmacokinetics, first edition 2012(reprint), published by
CBS publishers new Delhi. Page no.94-131
3. Paradkar Anant, Bakliwal Sunil, Biopharmaceutics and
pharmacokinetics, fourth edition 2013,published by nirali
parkashan Delhi, page no.4.1-4.14
4. https://en.m.wikipedia.org>wiki>biotransformation