Absorption and Distribution of Drugs
I.
Absorption
A.
The process by which a drug is transferred from the site of entry into
the body to the circulating fluids of the body.
B.
Rate of absorption is affected by:
1.
Route of drug administration
a.
Oral
b.
Parenteral
c.
Intravenous
d.
Inhalation
2.
Solubility of the drug
3.
pH of the body fluid –
a.
For a drug to cross a membrane barrier it must normally be soluble in the
lipid material of the membrane to get into membrane
b.
It has to be soluble in the aqueous phase as well to get out of the
membrane.
c.
Most drugs have polar and non-polar characteristics or are weak acids or
bases.
d.
For drugs which are weak acids or bases the pKa of the drug and the pH of
the GI tract fluid and the pH of the blood stream will control the solubility of
the drug and thereby the rate of absorption through the membranes, lining the GI
tract.
4.
Local conditions at the site of administration
5.
Drug concentration or dosage
II.
Drug Distribution
A.
The reversible transfer of drug from one location to another within the
body.
B.
Body size
C.
Circulatory dynamics
D.
Movement of the drug depends on circulatory status - Once a drug has
entered the vascular system it becomes distributed throughout the various
tissues and body fluids in a pattern that reflects
1.
The physiochemical nature of the drug
2.
The ease with which it penetrates different membranes.
3.
The “one compartment” model assumes rapid distribution but it does
not preclude extensive distribution into various tissues.
E.
Concentration of a drug at a specific site depends on:
1. The number of blood
vessels in a tissue
2.
The degree of local vasodilation
3.
The rate of blood flow to the site
F.
Also
1.
Protein binding
2.
Metabolism
3.
Excretion
G.
Distribution can be thought of as following one of four types of
patterns.
1.
The drug may remain largely within the vascular system. Plasma
substitutes such as dextran are an example of this type, but drugs which are
strongly bound to plasma protein may also approach this pattern.
2.
Some low molecular weight water soluble compounds such as ethanol and a
few sulfonamides become uniformly distributed throughout the body water.
3.
A few drugs are concentrated specifically in one or more tissues that may
or may not be the site of action.
4.
Most drugs exhibit a non-uniform distribution in the body with variations
that are largely determined by the ability to pass through membranes and their
lipid/water solubility. The highest concentrations are often present in the
kidney, liver, and intestine usually reflecting the amount of drug being
excreted.
Next
Page