4.Mechanism of drug absorption @passive diffusion

   Mechanism of drug absorption 

The principle Mechanisms for transport of drug molecules across the cell membrane in order of their importance  are

1.passive diffusion

2.pore transport 

3.facilitated diffusion 

4.active transport 

5.ionic or electrochemical diffusion 

6.ion-pair transport 

7.endocytosis

1.passive diffusion

-also called as non-ionic diffusion.

-it is the major process for absorption  of more than 90% of the drugs.

-the driving force for this process is the concentration or electrochemical gradient 

-it is defined as the difference in the drug concentration on either side of the membrane. 

-drug movement is a result of the kinetic energy if molecules.

-since no energy is required ,the process is called as passive diffusion. 

-during passive diffusion ,the drug present in aqueous solution partitions and dissolves in the lipid material of the membrane and finally leaves it by dissolving again in an aqueous  medium at inside of the membrane. 

-passive diffusion is best expressed by fickle first law of diffusion. 

*fickle first law of diffusion : the drug molecules diffusion from a region of higher concentration to one of lower concentration until equilibrium is attained and that the rate of diffusion is directly proportional to the concentration gradient across the membrane. 

-it can be mathematically expressed by the following 

Where dQ/dt=rate of drug diffusion        (amount/time).it also represents the  rate of appearance of drug in blood.

D=diffusion coefficient of the drug through the membrane (area/time)

A=surface area of the absorbing membrane for drug diffusion (area)

Km/w=partition coefficient of the drug between the lipoidal membrane and the aqueous GI fluids (no units)

(Cgit-C)=difference in the concentration of the drug in the GI fluids and the plasma,called as the concentration gradient (amount/volume).

h=thicknesses the membrane. 

-Based on the above equation,we may know that ;

1.the drug moves down the concentration gradient indicating down hill transport.

2.The rate of drug transfer is directly proportional to the concentration gradient between GI fluids&the blood compartment.

3.greater the area and lesser the thickness of the membrane, faster the diffusion;thus,more rapid is the rate of drug absorption from the intestine than from the stomach.

4.equilibrium is attained when the concentration of  either side of the membrane becomes equal.

5.drugs which can exist in both ionised and unionised forms;the rate of transfer of unionised species is 3 to 4 times the rate for ionised drugs.

6.greater the membrane/water partition coefficient of drug,faster the absorption. Since the membrane is lipoidal in nature,a lipophilic drug diffuses at a faster rate by solubilizing I  the lipid layer of the membrane. 

7.the drug diffuses high when the volume of GI fluid is low.

-dilution of GI fluid decreases when the drug concentration in these fluids (Cgit)&lower the concentration gradient (Cgit-C).

-this phenomena is however made use of in treating cases of overdose or poisoning. 

-passive diffusion is energy independent.

-the molecular weight of most drugs lie between 100 to 400 Daltons.

-diffusion of the compound decrease _when molecular weight increases. 

Sinkcondotion for drug absorption 

Once the passively absorbed drug enters the blood 》》it rapidly swept away》》distributed into a much larger volume of the body fluids 》》concentration of drug at the absorption site》》Cgit maintained greater than the concentration of drug in plasma.》》the condition is Called as sink condition for drug absorption.

-due to sink conditions, the concentration of the drug in plasma C is very small in comparison to Cgit.

-as a result,equation may be simplified to 

-the equation is an expression for a first order process.

-thus,passive diffusion follows first order kinetics.

-a large concentration gradient always exist at the absorption site for passive diffusion ,the rate of drug absorption is usually more rapid than the rate of elimination.

Note:

Pore diffusion  will be continued In  next blog