Factors affecting drug distribution within compartments

The body is divided into different fluid compartments & each contribute to certain amount of body weight

SOURCE : shuterstock.com

-Among Extracellular fluid  

a)Interstitial fluid      - 14L  (0.2% of BW)

b)Blood plasma         - 3.5L (0.05 % of  BW)

c)Lymph                    - 1.2 L (0.01% of BW)

-Intracellular fluid     -  28 L (0.57% of BW)

-Transcellular fluid    - 2.5L  (0.03% of BW)

-Fat                             -         (20% of BW )

    Drugs entering the body are distributed in these compartments. Keeping in mind of the plasma proteins only the drugs that are in free form are able to move between the compartments.

    Lipid insoluble drugs are mainly confined plasma and interstitial fluids. Lipid soluble drugs reach all the compartments and may accumulate in fat 

Apparent volume of distribution is defined as the volume that would contain the total body content of the drug at a concentration equal to that present in plasma concentration, Given by the formula 

                         V = Q / C_P

 

souce:https://www.researchgate.net/

Pattern of distribution of the drugs depends on these factors

  1) Permeability- 

      only small molecules can easily pass through - steroids, H₂O ,CO₂ & O₂ 

    

source:sciencemad.com

 2) Binding within compartment - 

      Drugs with high plasma protein (> 90% )binding causes them to be inactive, usually acidic drugs   fall under this category

source:cyprotex.com

  3)  pH partition - 

      According to the hypothesis, only unionized nonpolar drug can permeate the membrane and total concentration on each side of the membrane depends on the degree of  ionization.

Example is shown for a weak base with a pKa -6.4, Higher concentration is seen on the lower pH side of the membrane, opposite is true for a weak acid. Source: https://basicmedicalkey.com/

4)  Fat : water partition coefficient -

      Denotes the distribution of drug in fat and water. The more the value higher will be the distribution in Fat. Eg: Thiopental has a value of 10 hence it diffuses quickly into the tissues and has been used for induction of Anesthesia 

source:https://www.alamy.com/