Pharmacokinetics l Absorption, Distribution, Metabolism and Excretion l Study Pharma

Pharmacokinetics:
It is the quantitative study of drug movement in the body which involves the drug absorption, distribution, metabolism and excretion.
In simple manner: What the body does to the drug.
All the pharmacokinetics processes involve the transport of drug across the biological membrane.

Biological membrane:
This is a bilayer lipid membrane which capable of the lateral movement of drug. Drug transported acorss the membrane by
1. Passive diffusion and filtration     2. Specialized transport

1. Passive diffusion:
By the passive diffusion, drug diffuses across the biological membrane in the direction of concentration gradient means from high drug concentration region to low drug concentration region.
Advantages:
- No specialized transport mechanism required.
- Drug easily across the cell membrane.
Disadvantages:
- Only lipid soluble drug follow by this mechanism.
Filtration:
Lipid insoluble drug cross the biological membrane by the aqueous pores or paracellular spaces in the membrane is called filtration.

2. Specialized transport:
All the cell membrane express a transmembrane protein which serve as carrier or transporter which combines with their substrates (drugs) and transport the substrate on the other side of the biological membrane where transporter dissociate from the substrate and return back to its original state.
Specialized transport categories into:-
1. Facilitated diffusion     2. Active transport

Distribution:

Once the drug gained access to blood stream or circulation, it get distributed itself in the plasma or tissues.
The extent of distribution of drug is depends on various factors :-
- lipid solubility
- pka value of drug
- differential regional blood flow
- presence of specific tissue transporters
And the concentration gradient shift from plasma to tissue.

Volume of distribution or Apparent volume of distribution:
Assuming that the body is a single homogeneous compartment which act as to distributes the drug immediately or uniformly.

V = drug administered by i.v/ plasma concentration of drug

Reduction:

This reaction involves the addition of hydrogen / positively charged radical or removal of oxygen / negatively charged radical.

Involvement of cytochrome P450 enzyme which working opposite to oxidation.

Hydrolysis:
The reaction proceed in the presence of water to form metabolites.

Cyclization:
The reaction involves the formation of ring structure from straight chain compound and form metabolites.

Decyclization:
The reaction involves the opening of ring structure form into straight chain compound to form metabolites.

Biotransformation means the chemical alteration of drug in the body. Formation of inactive metabolite from active drug form.

- Convert the lipid soluble (non-polar) form into lipid insoluble (polar) form and excreted out from the body.
Biotransformation are categories into:-
1. Active drug -> Inactive metabolite
2. Active drug -> Active metabolite
3. Inactive drug -> Active metabolite

1. Active drug -> Inactive metabolite:
Active Drug form undergoes metabolism to form inactive metabolites which excreted out from the body.
Example:
Paracetamol, Ibuprofen, lidocaine etc.

2. Active drug -> Active metabolite:
Active Drug form undergoes metabolism to form active metabolites which again reabsorb through renal tubules into the circulation.
Example:
Digitoxin to Digoxin
Codiene to Morphine
Amitriptyline to Nortriptyline

3. Inactive drug -> Active metabolite:
Inactive Drug form undergoes metabolism to form active metabolites which again reabsorb through renal tubules into the circulation. Such types of drugs are called ' Pro drug's.
Example:
Levodopa to Dopamine
Proguanil to Cycloguanil
Prednisone to Prednisolone

Phase 2 reaction:
1. Glucuronide conjugation
Compound which contains hydroxyl or carboxylic acid are easily conjugated by glucuronic acid which derived from glucose.
The reaction carried out by UDP-glucuronosyl transfers (UGTs). Glucuronidation increases the molecular weight of drug and excreted in Nile.

2. Acetylation
Compound which contains amino or hydrazine groups undergo acetylation with the help of acetyl CoA.
The reaction carried out by N-acetyl transfers (NATs).

3. Methylation
Compound which contains amines or phenol groups undergo methylation by the methyl transferases (MTs)

4. Sulfate conjugation
Compound which contains phenol or steroid are sulfates by sulfotransferases (SULTs).

5. Glycine conjugation
Salicylates, nicotinic acid and carboxylic acid compounds are conjugated by glycine.

6. Glutathione conjugation
The reaction carried out by glutathione-S transferases

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