Drug distribution

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  After drug absorption, drugs distribute rapidly to tissues with high blood flow
and slowly to tissues poor in blood flow.  Cardiac output affects peripheral drug
penetration by increasing tissue perfusion.
Tissue accumulation:
Drugs may accumulate in tissues based on their physicochemical
characteristics or special affinity of the tissue for the drug. For example, lipid-soluble
drugs accumulate in adipose tissue because of drug partitioning. Tetracycline may
accumulate in bones because of complex formation with calcium.
Plasma protein binding:
Plasma protein binding affects drug distribution to a great extent. Drugs bound
to plasma proteins become unable to penetrate the tissues because of large size. Also
protein binding prolongs the action of the drug due to the presence of a bound form
of the drug  in equilibrium with the free form. The most important plasma protein is
albumin although other plasma proteins like α1-glycoprotein are important in binding
basic drugs like propranolol.  Potent drugs like phenytoin that are highly bound to
plasma proteins (over 90%) may be displaced by other drugs that are also highly
protein-bound (salicylates)  resulting  in drug displacement and increase of the free
form of the drug resulting in increased drug toxicity.
Penetration of the blood brain barrier (BBB):
  The capillaries of the brain are surrounded by a thick lipid membrane layer of
glial cells that create what is called BBB. Only lipophilic drugs can pass this barrier readily.
Placental transfer of drugs:
  The maternal and fetal blood are separated by what is called blood placental
barrier.  Lipid-soluble drugs pass readily to the fetus while water-soluble drugs,
specially large molecular weight drugs, pass slowly. Even though, all drugs should be
considered to be transported to the fetus for the  purpose of taking precautions to
avoid drug-induced malformation.
Redistribution:
  Termination of drug action is usually produced by drug biotransformation or
excretion. However, drug redistribution may terminate drug effect. For example, the
highly lipid-soluble ultra-short acting barbiturate (thiopental)  rapidly penetrates the
blood brain barrier causing CNS depression. However, the drug rapidly redistributes
from the site of action to adipose tissue resulting in rapid fading of the effect.  

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