Drug metabolism is simply making the drug more water soluble for excretion. Excretion of drug simply means that removing of drug from our body by means of urine, faeces, exhaled air, saliva, sweat, milk, etc.

As mostly the drug is lipid soluble, we have to make it water soluble to eliminate it from our body, so our body carries out some biological reactions with that drugs and make it water soluble.

The whole is a part of Absorption, Distribution, Metabolism and Excretion are the part of Pharmacokinetics.

What you get below?

  1. Drug Metabolism/Biotransformation
  2. Metabolism of drug leads to?
  3. Pro-drugs
  4. Types of Metabolism
  5. Inhibition of drug metabolism
  6. Microsomal enzyme induction
  7. First pass metabolism
  8. Excretion of Drug
  9. Excretion in the form of?
  10. Clinical significance of Excretion
  11. Conclusion
  12. Frequently Asked Questions (FAQs)


Biotransformation or drug metabolism is defined as it is the chemical alteration of the drug in the body by transforming it from non-polar (lipid soluble) to polar (water soluble), so that it can be excreted easily.

Mostly all the lipid soluble drug undergo metabolism. Most hydrophilic drugs such as Neostigmine, Streptomicin, etc are excreted without biotransformation.

As this is our body’s defense mechanism that toxic matter are turned to their inactive form and are eliminated readily.

This biotransformation or drug metabolism occurs in certain organs such as majorly liver and others may be kidney, intestine, plasma, lungs.

Metabolism of drug leads to?

  1. Inactivation.
  2. Active metabolites from active drug.
  3. Activation of inactive drug.
Active drug to Inactive metabolite
Active drug to Active metabolite
Inactive drug to Active metabolite   


Pro-drugs are those drugs which are inactive when administered but turns active when metabolism.

Example is when L-dopa is administered it is in inactive state but when metabolized it turns to dopamine which is in active state.


Pro-drugsActive metabolite
Prednisole Prednisolone

Types of Metabolism

Non-synthetic reaction:

1. Oxidation:

Oxidation reaction is simply addition of oxygen/negatively charged radical or removal of hydrogen/ positively charged radical. This reaction of biotransformation is the most common amongst all the other.

Oxidation reaction involves many reactions such as hydroxylation; oxygenation, N or O-dealkylation, oxidative deamination. In some cases initially additions of oxygen the compounds like superoxide, epoxide, etc are form but further they form a stable metabolite.

These reactions are generally carries out using the biological catalyst or enzyme mono-oxygenases in liver, which further involves Cytochrome P-450 enzyme to carry out the metabolism.

Examples of the drugs which undergo oxidation are Barbiturates, Benzodiazepines, Paracetamol, Hydantoins, Theophylines and many others.

2. Reduction:

Reduction reaction is simply addition of hydrogen/ positively charged radical or removal of oxygen/negatively charged radical. In this reaction Cytochrome P-450 enzyme works in opposite manner.

Examples of the drugs which undergo reduction are alcohols, aldehydes, quinines like warfarin, halothane, chloralhydrate, chloramphenicol, etc.

3. Hydrolysis:

Hydrolysis is a reaction in which there is cleavage of bond between molecules in the presence of water.

In our body certain enzymes like amidase and peptidase are present who cleaves Amides and peptides in the presence of water. Hydrolysis reaction takes place in Liver, Intestine, Plasma, and some tissues.

Examples of the drugs which undergo hydrolysis are oxytocin, aspirin, pethidine.

4. Cyclization:

In this reaction the straight chain compound is converted to ring structure, this process is known as cyclization.

5. Decyclization:

In this reaction the ring structured compound is converted to straight chain compound, this process is known as decyclization.

Synthetic reaction:

       REACTION        REACTION OF           EXAMPLE
Glucuronide conjugationCompounds containing carboxylic acid and hydroxyl group Aspirin, Phenacetin, Morphine, Chloramphenicol.
Acetylation Compounds containing amino or hydrazine group Isoniazide, Sulfonamide, Hydralazine.
MethylationCompounds containing amines and phenolsMethionene, Adrenaline, Histamine, Nicotinic acid.
Sulfate conjugationCompounds containing phenols and steroidsChloramphenicol, Adrenal and sex steroids.
Glycine conjugationCompounds containing Salicylates and carboxylic acids.Salicyaltes
Glutathione conjugationCompounds containing Quinone or EpoxideParacetamol
Ribonucleoside/ Nucleotide synthesisCompounds containing Purine and pyrimidine activationPurines and pyrimidines.

Inhibition of drug metabolism

Inhibition of drug metabolism means when two drugs utilizes same enzyme for its metabolism, the drug containing more affinity will inhibit the metabolism of another drug containing less affinity.

Drugs that inhibit the enzymes are:

FluoxetineHIV protease inhibitorsltraconazoleKetoconazole
MAO inhibitorsOmeprazoleRitonavirVerapamil

Microsomal enzyme induction

Microsomal enzyme induction is a process by which a drug increases the synthesis of the Microsomal enzymes. This process increases the metabolism of the same drug or the other drug having affinity to same enzyme.

Clinical significance of Microsomal enzyme induction:

  1. Increase the intensity of drug that has became active after metabolism.
  2. Decrease the intensity of drug that has became inactive after metabolism.
  3. Proper adjustment of dose is necessary.
  4. Tolerance develops.
  5. Can be in use during drug poisoning.

First pass metabolism

In case of some drugs, the part of drug biotransforms, before entering into systemic circulation, this process of metabolism of known as first pass metabolism. This process generally occurs in Liver.


Now as the drug is metabolized meaning the drug has become polar or water soluble, it is ready to be excreted. This process is elimination of waste matter from our body.

This process is actually a defence mechanism because as the drug is foreign material it may produce toxicity if it remains in our body for longer time, so it should be excreted from our body as soon as possible after its work has been completed.

Excretion in the form of ?

1. Urine:

Kidney is the main organ of our excretory system, is does the work of eliminating the water soluble material from urine. The main composition of urine is urea other composition is metabolites that forms in our body.

2. Faeces:

The larger molecules which can’t be excreted through urine, is created from faeces.

The bile derivatives are the main excretory material in faeces. Liver produces bile which works as breaking down the fats or oil soluble material.

The larger molecules which are greater than molecular weight of 300 are excreted through bile.

What kind of drugs is eliminated through faeces?

  1. Drugs that diffuses back from blood to intestine.
  2. Drugs that excretes from bile.
  3. Medicines that are acts in intestine like neomycin, after the action it is excreted into the faeces.
  4. The unabsorbed fraction of drug.

Certain drugs that are excretes directly in colon of human excretory system are Heavy metals, Anthracene purgatives.

3. Exhaled air:

Gases like general anesthetics or any other gases which are inhaled from nose are excreted from exhaled air only. The volatile liquids like paraldehyde, alcohols, are excreted through exhaled air from lungs.

This elimination is independent of lipid or water solubility. What matters is partial pressure of blood and pressure in lungs.

4. Saliva and Sweat:

This method of elimination is least important because only traces of waste are excreted from this route. The ions like lithium, iodide, thiocyanate and heavy metals are eliminated in traces.

5. Milk:

Excretion by milk is only seen in lactating mother, the waste material from mother body travels into milk by passive diffusion.

It may be not important to mother, but it is dangerous to the child because it feeds on the milk initially. Milk has ph 7 which is lower than plasma.

Renal Excretion

Renal excretion includes many processes such as Glomerular filtration, Tubular reabsorption, Tubular secretion, and Excretion. As kidney is responsible for eliminating all the water soluble material from our body, renal excretion is phenomenon related to kidney itself. (Mostly Excretion is after Drug metabolism).

This system is not well developed during birth; it starts developing as the age proceeds. As a result, duration of action is longer in neonates or children as compared to adults. 

The principle of this renal excretion is to eliminate the poisonous substance from human body. Rate of eliminating is mostly dependent on concentration of drug. Tubular secretion of drug is active process.

Clinical significance of Excretion:

  1. In case of renal disease, excretion by faeces is done.
  2. Heavy materials can be excreted.
  3. Drugs acting near intestine can be excreted.
  4. Kinetics of drug elimination can be studied.
  5. Toxic materials can be eliminated.
  6. Unused drug can be eliminated.
  7. Excess amount of water can be excreted.
  8. Poisoning from drug can be prevented.


Pharmacokinetics processes include Absorption, Distribution, Metabolism, and excretion of drug. All these processes we have studied now and in previous blog.

Metabolism of drug is conversion of drug into excitable form. After metabolism drugs are converted into active or inactive state.

Metabolism activates the pro-drugs. Pro-drug enhances the activity of the actual drug by giving more bioavailability because it gets converted to active drug after metabolism.

Phase 1 metabolism produces active metabolites, phase 2 metabolism produce inactive metabolites.

Enzyme induction and inhibition decreases or increases the drug metabolism. Rate of elimination depends on concentration of drug to be eliminated.

Frequently Asked Questions (FAQs)

1. When metabolism is high?

Metabolism becomes high when enzyme inhibitor is administered with the drug.

2. When metabolism slows down?

Metabolism slows down when enzyme inducer is administered with the drug.

3. When metabolism works?

Metabolism works when there is any lipid soluble material is administered in the body.

4. Are metabolism boosters safe?

A metabolism booster means enzyme inducers. They are safe relative to cases but should be administered only when a registered medical practitioner prescribes it.

5. Why metabolism is important?

Metabolism is important to make the toxic drug inactive.

6. Can metabolism burn fat?

Metabolism don’t directly burn fat, it induces the fat burning.

7. Excretion of drug depends on?

Excretion depends on water retention and concentration of drug.

8. What is the work of bile in excretion?

Bile is the fluid produced by liver, the work of the bile is to breakdown the fats or lipids or oil soluble material. Further the broken fat is excreted through faeces.



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