biotransformation of drug(metabolism) for b.pharma,m.pharma students.

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