Distribution Of Drug Molecules

                        DISTRIBUTION OF DRUG

Once a drug enters into systemic circulation by absorption or direct administration, A drug has to be distributed into interstitial and intracellular fluids.
The lipid solubility, pH of compartment, extent of binding with plasma protein and tissue proteins,cardiac output, regional blood flow, capillary permeability are associated for distribution of the drug trough tissues. The drug is easily distributed in highly perfused organs like liver, heart, kidney etc in large quantities & in small quantities it is distributed in low perfused organs like muscle, fat, peripheral organs etc.

• The drug can be moved from the plasma to the tissue until the equilibrium is established (for unbound drug present in plasma).
• The drug, for reaching the low perfused organs takes more time (Up to many hours) but it is necessary because the large mass fraction is present in low perfused area because of having more amount in body than higher perfused one.
• The drug can be moved easily from blood to tissue because of higher vascular permeability of capillary epithelium except brain.
• The lipid solubility and pH difference between two compartments is also important for movement of drug from blood to tissue.

BODY COMPARTMENT

• Body fluid means water and its dissolved solvent.
• Around 45 to 75% of the body weight, water is present in the body.
• It is gradually more in men(60%) then women ( 55%) ,The infants have the highest % of water upto 75 % of body weight. This % decreases with age.
• Adipose tissue contains no water, thus fatty persons have low volume of water.
• Mainly body fluid is distributed in body into 2 compartments
  
  o Intracellular fluid (ICF) - It involves the fluid present in the cells of the body. ( 1/3rd of body weight)
  o Extracellular fluid (ECF) - ECF involves blood plasma, interstitial fluid, & lymph. (2/3rd of body weight).
• The fluid also present as a transcellular form, present in the cavities made up of cells like CSF, Intra ocular fluid (IOF), Pleural, Peritoneal, Synovial, Digestive secretions etc, This type of fluid is produced by the cells present nearby to that organ.
• The drug molecules are present in this type of body compartment of fluid as free & bound form.
• If body acts as single compartment, the volume that contains the drug present in the body called as apparent volume of distribution. (Dv).
• Distribution means not only a dissolution of drug into body fluid but also binding & sequestration.
• Lipid insoluble drugs can’t enter into the cell and they are distributed in ECF.

Drugs distributed in ECF
      Insulin, Sucrose, thiosulfate, sulfate, chloride, bromide & sodium belongs to this class.
      The volume of distribution of these substances vary considerably. Ex- Sulfate distributed in about 22% of body weight extra cellularly .

Drug distributed through out Body water
      The drug which are smaller and can be passed with water like urea, alcohol etc, can be diffused through capillaries into the ECF but lipid soluble drugs can be diffused at a faster rate & Dv is more in the ECF.
      N.B: The drugs which are given intravenously can be distributed faster rate.