biopharmaceutics and pharmacokinetics, drug biotranformation

1. DRUG BIOTRANSFORMATION
DEPT. OF PHARMACEUTICS
SREE DATTHA INSTITUTE OF PHARMACY,
SHERIGUDA, IBRAHIMPATNAM, HYDERABAD, 501510.
SREE DATTHA INSTITUTE OF PHARMACY
Under the guidance of:
Asst.prof. Naga Chandrika, M. Pharm
Submitted by:
K. Anusha Reddy
16U21R0011
B. Pharmacy IV Year
1

2. CONTENTS:
• DEFINITION
• NEED FOR DRUG BIOTRANSFORMATION
• FUNCTIONS
• DRUG METABOLISING ORGANS
• DRUG METABOLISING ENZYMES
• TYPES
• FACTORS AFFECTING BIOTRNSFORMATION OF DRUGS
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3. DEFINITION:
◦ It is defined as the chemical conversion of one form to another form of drugs.
◦ Chemical alteration of drugs in the body.
◦ Non polar lipid soluble compounds are made polar lipid insoluble, so that they are
easily excreted.
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4. NEED FOR DRUG
BIOTRANSFORMATION:
◦ Drug biotransformation generally eliminates the xenobiotics from the body.
◦ When we take food it gets metabolized and excreted ,for effective metabolism or
absorption the drug should be lipophilic and non-ionic.
◦ Whereas lipid soluble substance are passively reabsorbed from the renal tubules into
the blood after glomerular filtration. thus if such phenomenon continues drugs
would accumulate in the body and cause toxic reactions.
◦ However to prevent from such consequences the drug should be transformed into
hydrophilic and ionic form that can be easily excreted through kidneys.
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5. FUNCTIONS:
A) DRUG INACTIVATION: It results in formation of metabolites with little or no
pharmacological activity.
Example: Conversion of phenytoin to p-hydroxy phenytoin .
B) ACTIVE DRUG TO ACTIVE METABOLITE: It results in formation of
metabolites with high tissue reactivity .
Example: Phenacetin - Paracetamol
Phenylbutazone - Oxyphenbutazone.
C) INACTIVE DRUG(PRODRUG) – ACTIVE DRUG: Prodrugs re inactive
drugs which need biotransformation to form active metabolites.
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6. DRUG METABOLISING ORGANS:
LIVER is the primary site for the metabolizing of almost all drugs because of its
richness of processing a large variety of enzymes in large amounts.
Metabolism by organs other than liver is of minor importance since lower level
of metabolizing enzymes are present in such tissues.
The decreasing order of drug metabolizing ability of various organs is:
LIVER > LUNGS > KIDNEYS > INTESTINE > PLACENTA
>ADRENALS > SKIN.
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7. DRUG METABOLISING
ENZYMES:
A number of enzymes in animals are capable of metabolizing drugs .the
enzymes are located mainly in the liver , but may also be present in other organs
like lungs, kidneys, intestine, brain, plasma etc.
Majority of drugs are acted upon by relatively non-specific enzymes which are
directed to types of molecules rather than to specific drugs.
It is divided into two types:
MICROSOMAL ENZYMES
NON – MICROSOMAL ENZYMES
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8. MICROSOMAL ENZYMES:
The endoplasmic reticulum of liver and other tissues contain a large variety of
enzymes together called microsomal enzymes.
They catalyze glucuronide conjugation ,most oxidative reactions and
hydrolytic reactions.
NON- MICROSOMAL ENZYMES:
Enzymes occurring in organelles other than endoplasmic reticulum are called
non – microsomal enzymes..
They catalyze a number of reductive and hydrolytic reactions and all conjugative
reactions other than glucuronidation.
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9. TYPES:
◦ PHASE 1 REACTIONS / NON SYNTHETIC / FUNCTIONALIZATION:
A functional group is generated.
Metabolite – active or inactive.
◦ PHASE 2 REACTIONS / SYNTHETIC / CONJUGATION:
An endogenous radical is conjugated.
Metabolite is usually inactive.
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10. FACTORS AFFECTING
BIOTRANSFORMATION:
◦ CHEMICAL
◦ BIOLOGICAL
◦ ALTERED PHYSIOLOGICAL
◦ TEMPORAL
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11. CHEMICAL FACTORS:
◦ ENZYME INDUCTION
◦ ENZYME INHIBITION
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12. ENZYME INDUCTION:
◦ It is a process in which a drug induces or enhances the expression of an
enzyme.
◦ RIFAMPACIN if taken by female patients taking contraceptives causes
decreased therapeutic effect , leading to pregnancy.
◦ PHENOBARBITONE if administered to patients taking warfarin may cause
therapeutic failure, leading to increased bleeding tendency.
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13. ENZYME INHIBITION:
Decrease in the drug metabolizing ability of enzymes. When enzyme inhibitor
attaches less metabolism occurs.
Example:
◦ SULFONAMIDES decrease the metabolism of phenytoin so that its blood
levels become toxic.
◦ CIMITIDINE decrease the metabolism of propanol leading to enhanced
bradycardia.
◦ ORAL CONTRACEPTIVES inhibit metabolism of antipyrine.
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14. BIOLOGICAL FACTORS:
AGE:
In elderly most processes slow down which leads to decreased metabolism.
Shrinkage of organs occurs as well along with decreased liver functions and
decreased blood flow through the liver. All these factors the metabolism.
The drug doses should be decreased in the elderly.
DIET:
The enzyme content and activity is altered by a number of dietary components.
Low protein in diet decreases and high protein content in diet increases the drug
metabolizing activity.
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15. ALTERED PHYSIOLOGICAL
FACTORS:
◦ PREGNANCY
◦ DISEASE STATES
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16. PREGNANCY: During pregnancy metabolism of some drugs is increased while that
of others is decreased due to presence of steroid hormone.
Diseased states:
◦ LIVER DISEASE such as hepatic carcinoma, cirrhosis, etc. reduce the hepatic
drug metabolizing ability and thus increase the half lives of almost all drugs .
◦ IN RENAL DISEASE conjugation of salicylates, oxidation of vitamin D and
hydrolysis of procaine are impaired.
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17. TEMPORAL FACTOR:
◦ Diurnal variations and variations in enzyme activity with life cycle is
CIRCADIAN RHYTHM.
◦ Enzyme action is maximum during early morning and minimum in late
afternoon which is probably due to high levels of coticosterone.
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18. Reference:
BOOK:BIOPHARMACEUTICS AND PHARMACOKINITICS
AUTHOR:D.M.BRAHMAKAR
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19. Thank You.
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