Mechanism of GIT absorption of drug

The cell membranes of GI barrier are lipoprotein structure which act as semipermeable membranes allowing rapid transit of lipid soluble molecules, the passage of water & hydrophilic molecules through aqueous pore.

There are two main mechanisms of drug transport across the GI epithelium

1.    passive diffusion

2.    carrier- mediated transport

a.     active transport

b.    facilitated transport

3.    others

1.    Passive diffusion: is the major process of most drugs to cross cell membrane of GIT.

Mechanism of passive diffusion: drug molecules pass across the membrane from high concentration in the lumen to low concentration in the blood.

The rate of transport is determined by Flick's law of diffusion

                    dQ/dt =DAK (Ca-Cp)/h

Where  dQ/dt is the rate of diffusion

             D is the diffusion coefficient

             A is the surface area of the membrane

             K is the lipid-water partition coefficient of the drug

             H is the thickness of the membrane

           (Ca-Cp) is the differences between the drug conc. at the                                      absorption site & in the plasma

The rate of passive absorption of weak electrolyte is related to the fractions of the total drug that exists in the unionized form in solution in the GI fluids at the absorption site. This fraction is determined by the dissociation constant (pKa value) &by the pH of the aqueous medium.

Henderson-Hasselbalch equation describes the relationship between pKa & pH.

For an acid:

                  A-H→ A­-+ H+

pH= pKa + log    ionized conc. (salt)       = log (A-) /(A-H)

                            Unionized conc. (acid)

For base:           

                 B → B- + BH+

pH= pKa + log    unionized conc.(base)          = log( B ) /(BH+ )

                                Ionized conc. (salt)

2.    Carrier-mediated transport:

a.    active transport mechanism: is carrier-mediated transmembrane

·       Process which plays an important role in the GI absorption, in renal & bilary secretion of many drug & metabolites.

·       Active transport requiring carrier that binds the drug to form carrier-drug complex which across membrane and then dissociates on the other side of the membrane (transported against a conc. gradient & need energy )

·       The carrier returns to its initial position in the surface of cell membrane.

a.    facilitated transport: it is also Carrier-mediated transport system differing from active transport in that

•  the drug move along conc. Gradient

• the system does not require an energy

3.    other

              a. Ion-pair absorption: interaction of such drug ions with endogenous organic ions of opposite charge to form absorbable neutral species (ion-pair)

                      e.g.: quaternary ammonium compounds &                                         tetracycline

             b. Convective absorption (pore transport): very                         small molecules such as sugars &water are able to                      cross cell membranes as if the membrane contained                      aqueous filled channels or pores.

             c. Vesicular transport: is the process of engulfing                        particles or dissolved materials by the cell.

• Pinocytosis refer to small solutes

•   Phagositosis refer to large particles e.g. polio vaccine & fat soluble vitamins.