Pharmacokinetics

Bahaa EL Merhabi
 Definition

Pharmacokinetics is what the body does to the drug

Can be summarized as ADME where:

A= absorption

D= distribution

M= metabolism
Elimination process
E= excretion
 Cell membrane
It’s semi-permeable
Composition:

1- Structural proteins : structure and support

2- transport proteins
1- proteins: 3- receptor proteins : communication
4- glycoproteins : transporters and communication

1- Phospholipids : bilayer organized in a

2- lipids specific way.
2- cholesterol

On the external part that is facing the

3- Carbohydrates
aqueous extracellular environment
 Mechanisms of transport through
the cell membrane

1- simple diffusion

2- carrier mediated transport

2.1- active transport

2.2- passive facilitated diffusion

3- filtration

4- endocytosis/exocytosis - pinocytosis
 1- simple diffusion or passive diffusion
 1- involves lipid soluble molecules that pass transcellularly ( through the lipid bilayer)
2- involves small water soluble molecules ( up to 600 Da like alcohol) that pass paracellularly
( through aqueous pores)
3- water and ions through filtration through aqueous pores
4- No energy need
5 – not saturable, no competitive inhibition and no specificity
6- down a concentration gradient
7- quantified by Fick's law of diffusion :

Rate of diffusion=
D is diffusivity or diffusion coefficient :
It depends on the : - lipid solubility
- molecular weight Of the molecule
- the molecular conformation
( ionized or non ionized)

 
Weak acid ( pKa) ( ):  
Weak base ( pKa) (:
pH < pKa  HA predominant ( uncharged )  well absorbed pH < pKa  BH+ predominant ( charged )
pH > pKa  A- predominant ( charged) pH > pKa  B predominant ( uncharged)  well absorbed
  is the partition coefficient:
Pc
It reflects the relative solubility of the molecule M in lipid and in water
Calculated as Log(P) where

When [M]l > [M]w  P>1  log(P) > 0  high lipid solubility and high diffusion

Sa : surface of the diffusion membrane

d : thickness of the diffusion membrane

 Carrier mediated transport
More rapid than simple diffusion

Active transport( big water Passive facilitated diffusion ( as

soluble molecules) glucose into the RBC)
1- specific  possibility of competitive 1- specific  possibility of
inhibition competitive inhibition
2- need carrier  saturable 2- need carrier  saturable
3- need energy and usually coupled to 3- DO NOT need energy
ATPase 4- down a conc. gradient
4- can be against a conc. Gradient
e.g. at least 2 in the kidney and 4 in the
liver , BBB, choroid plexus
 filtration

1- for water and small charged and

water soluble molecules (ethanol,
glycerol , methanol and salts)
2- very important for urinary excretion.
 Endocytosis - pinocytosis
Endocytosis Pinocytosis ( cell drinking)

selective Not selective

Receptor mediated, the molecule to be Not receptor mediated, the solutes

endocytosed attaches to it’s specific surrounding the cell could enter by
receptor then endocytosis pinocytosis

Both need energy