Dr.

Asmaa El-rakhawy
Lecturer of clinical pharmacology
Faculty of Medicine/Mansoura University

Asmaa_pharma2013@yahoo.com
01062692218
 Lecture 2
Pharmacokinetics (2)
 ILOs

1. What is the meaning of drug Distribution

2. Define the Vd & its clinical importance

3. Describe the plasma protein binding & its

clinical significance

4. Define Drug Metabolism & its sequences

 Distribution
☺ It is the reversible transfer of drugs
between body fluid compartments.

⚫ Sites of drug distribution

Plasma = 3 L
Extracellular water = 9 L
Intracellular water = 29 L
 Volume of distribution (Vd)
❑ Definition: The apparent volume of water into which the drug is
distributed in the body

❑ Clinical significance:
➢ Determination of the site of drug distribution
❖ If the total Vd:
A. < 5 L: drug is confined to the plasma & can be removed
by dialysis (in case of drug toxicity).

B. 5 -15 L: drug is restricted to the extracellular fluid (ECF)

(depends on the case).

C. > 41 L: drug is highly bound to tissue proteins & cannot

be removed by dialysis.
❑ Binding of drugs to plasma proteins
➢ Most drugs into the blood are bound to plasma proteins (mainly albumin). So
there is free part & bound part of a drug
❑ Clinical significance:
1. The effect of the drug is related to its free part
(the bound part acts as a reservoir from which the drug is
slowly released).

2. Drugs binding to plasma proteins prolongs their effects.

3. Any small displacement of the bound part of a drug with high
plasma protein binding by another drug can lead to dramatic
toxicity {as warfarin}

4. Chronic liver disease & renal failure can affect the level of
albumin thus causing serious problems with some drugs.
 Metabolism
➢ It is the conversion (biotransformation) of the
drug into another form

➢ Many lipid soluble drugs must be converted into

a water-soluble form (polar) to be excreted.

➢ Some drugs are excreted unchanged.

The liver is the major site of drug metabolism

▪ Other organs can also metabolize drugs e.g.

kidney, lungs…..
 ❑ Metabolism of drugs may lead to conversion of:
1. Active drug into inactive metabolites → termination of the effect.

2. Active drug into active metabolites → prolongation of the effect

e.g. codeine is metabolized to morphine

3. Inactive drug (pro-drugs) into active metabolites → activation

e.g. enalapril is metabolized to enalaprilat

4. Non-toxic drug into toxic metabolites

(in case of paracetamol overdose → toxic product N-ABQI).
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