Factors Affecting Drug Distribution

Drugs distribution is affected by :

Age : Distribution varies with difference in :

1. Total Body Content (Intracellular and Extracellular) : It is maximum in infants.
2. Fat Content : Greater in infants and in elder ones.
3. Skeletal Muscles : Less in infants and elderly people.
4. Organic Composition : Poorly developed BBB, low myelin content and high cerebral blood flow are stated in infants causing greater drug penetration in the brain.
5. Plasma Protein Content : Albumin content is low in both infants and aged people.

Pregnancy : Growth of uterus, placenta and foetus raises volume for drug distribution, in pregnancy. Drug may also be distributed in foetus which acts as separate compartment. Plasma and ECF volume also increases but albumin content is reduced.

Obesity : High adipose tissue content results to low drug distribution and perfusion. High fatty acid content alters the binding property of acidic drugs.

Diet : Fat rich diet increases free fatty acid concentration in the blood that affects binding of acidic drugs e.g., NSAIDs, albumin, etc.

Disease States : Drug distribution is severely affected in diseased conditions, such as;

1. Alteration in albumin and other drug-protein concentration.
2. Reduced or altered perfusion to organs and tissues.
3. Alteration in tissue pH.

In case of patients of encephalitis and meningitis, the blood-brain barrier (BBB) become more permeable, therefore, concentration of the ionic antibiotics (e.g., as penicillin G and ampicillin) increases in tissues of brain; that does not occur normally. In case of patients of CCF, there is fall in perfusion rate to entire body due to this distribution of each drug is affected.

Drug Interaction : Two or more drugs administered together compete for binding site and tend to replace each other, and a free drug may cause lethal effects, eg., phenylbutazone and warfarin.