I am a pharmacist. These slides describe topic elimination of drug. I hope pharmacy department students get more benefits about it.

1. Dr.
Muhammad
Usman
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Dr. Muhammad Usman
Elimination of Drugs

2. Drug Elimination
Dr.
Muhammad
Usman
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Drug
Elimination
Metabolism
Liver
Excretion
Kidney
Lungs
Skin
GI
Mucosa
Microbial
Flora
Kidney

3. Dr.
Muhammad
Usman
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Drug Elimination
Factors affecting drug
Elimination
Renal
Disease
Hepatic
Disease
Drug
Interactions
Drugs that are eliminated by metabolism (Phenytoin,
Theophyllin, Lidocain etc) demonstrate high Inter-Individual
Variability (IIV) in elimination half life.
Drugs that are eliminated through kidney demonstrate less
Inter-Individual Variability (IIV) on elimination half life.

4. • The elimination rate constant (k) is the sum of the first-order rate
constant for metabolism (km) and the first-order rate constant for
excretion (ke).
Generally, the excretion rate constant (ke) is easily evaluated for
drugs that are primarily renally excreted.
• Nonrenal drug elimination is usually assumed to be due for the
most part to hepatic metabolism,
• As metabolism can occur in any organ or tissue that contains
metabolic enzymes. Therefore, the rate constant for metabolism
(km) is difficult to measure directly and is usually obtained from
the difference between k and ke.
Dr.
Muhammad
Usman
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First order elimination

5. • The hepatic biotransformation enzymes play an important role
in the elimination of drugs that are not easily cleared through
the kidney
• For most biotransformation reactions, the metabolite of the
drug is more polar than the parent compound.
• The conversion of a drug to a more polar metabolite enables
the drug to be eliminated more quickly than if the drug
remained lipid soluble.
• A more polar metabolite does not cross cell membranes easily,
is filtered through the glomerulus, is not readily reabsorbed,
and is more rapidly excreted in the urine.
Dr.
Muhammad
Usman
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Drug Biotransformation
Reactions

6. Dr.
Muhammad
Usman
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Drug Biotransformation
Reactions

7. Pathways of
Biotransformation
reactions
Phase-I
(Asynthetic)
Phase-II
(Synthetic)
Dr.
Muhammad
Usman
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Drug Biotransformation
Reactions
Oxidation
Reduction
Hydrolysis
Acetylation
Sulfonation
Methylation
Glucoronidation
Conjugation
The drugs that resemble natural biochemical
molecules are able to utilize the metabolic
pathways for normal body compounds
e.g Isoproterenol by COMT
Amphetamin by MAO

8. Dr.
Muhammad
Usman
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Phase-I Reactions
Usually, phase-I biotransformation reactions occur first and
introduce or expose a functional group on the drug molecules.
Examples
Phenylbutazone Oxyphenylbutazone
Oxidation
Demethylation
Morphine
Codeine
Acetyl Salicylic acid Salicylic acid Acetic acid
Hydrolysis
Hydrolysis
Benzocaine PABA Benzene

9. Dr.
Muhammad
Usman
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Phase-II Reactions
Once a polar constituent is revealed or placed into the molecule, a
phase II or conjugation reaction may occur.
Examples
Glycine Conjugation
Salicylic acid Glycine
Salicyluric acid
Salicylic acid Glucuronic acid Salicylglucuronic acid
Glucuronidation
Glycine
Benzoic acid Acetyl Co-A Benzoyl Co-A
Benzoyl Co-A Hippuric acid
Acetylation
Glycine Conjugation