The document discusses biotransformation, which is the chemical alteration of drugs in the body. The body treats drugs as foreign substances and converts them into more polar, water soluble compounds through biotransformation so they can be excreted through the kidneys. Biotransformation occurs primarily in the liver and involves two phases - phase I reactions change the drug through processes like oxidation and phase II involves conjugating the drug to make it inactive so it can be excreted. Factors like other drugs, food, and an individual's characteristics can impact the biotransformation of drugs through inhibition or induction of the enzymes involved.

1. Biotransformation
Dr. Jervin Mano

5. Introduction
 Body treats most drugs as foreign substances and tries to
inactivate them and eliminate them.
 They convert the drugs into more polar , water soluble
compounds so that they can be easily excreted through the
kidneys.

6. Biotransformation of drugs
Chemical alteration of the drug in the body
Drugs may be
 Excreted unchanged
 Metabolized by enzymes
 Spontaneously changed

7. CONSEQUENCES
 Inactivation
 Paracetamol
 Lidocaine
 Propranolol
 Active metabolite from an active drug
 Codeine, Morphine
 Activation of an inactive drug
 Prodrug :- Initially inactive converted in body to active form
 Advantages – Stable, better bioavailability, less toxic
 Levodopa Dopamine

8. Sites of biotransformation-
Liver
Plasma, kidney, lung, gut wall

9. Types of biotransformation reaction
Phase I
 Non synthetic/Degradative
 changes drugs and creates site
for phase II
 Metabolite:- Active/Inactive
 Types:-
 Oxidation
 Reduction
 Hydrolysis
 Cyclization
 Decyclization
Phase II
 Synthetic/ Conjugation
 group added to existing (or phase I
formed) conjugation site
 Metabolite:- Inactive
 Types:-
 Glucuronide conjugation
 Sulphate conjugation
 Glutathione conjugation
 Glycine conjugation
 Methylation, Acetylation

10. ENZYMES FOR BIOTRANSFORMATION
Microsomal enzymes
Present in smooth surfaced ER of liver
Mixed functn enzymes & cyt P-450
Involved in phase I reactions & glucuronide
conjugation(Phase II)
Non-microsomal enzymes
Present in plasma, cytoplasm,mitochondria
Involved in all phase II reactions except
glucuronide

11. Non enzymatic biotranformation
 Hoffman’s elimination
 Metabolised spontaneously in the plasma
 Eg ;- Atracurium

12. Inhibitors and inducers of microsomal enzymes
INHIBITORS
Inhibits Cytochrome P450-> Inhibits metabolism of certain
drugs
Eg. Cimetidine, ketoconazole, ciprofloxacin
INDUCERS
Synthesis of microsomal enzymes enhanced by certain drugs
-> Speeds up metabolism of drugs
Eg: barbiturates, carbamazepine , Alcohol, Cigarette smoke.

13. Factors affecting biotransformation
Race (CYP2C9; warfarin (bleeding) phenytoin (ataxia) Losartan
(less cleared but less activated as well); also fast and slow
isoniazid acetylators
Age (reduced in aged patients & children)
Sex (women slower ethanol metabolizers)
Species
Clinical or physiological condition
Other drug administration (induction or inhibition)
Food
charcoal grill ++CYP1A
grapefruit juice --CYP3A
 First-pass metabolism

14. Summary
 Definition of biotransformation
 Primary site of metabolism
 Prodrug
 Types of biotransformation reactions
 First pass metabolism
 Enzyme inducers
 Hoffman’s elimination