Miscellaneous Factors Affecting Drug Distribution

MISCELLANEOUS FACTORS AFFECTING DRUG DISTRIBUTION

Age

Differences in distribution pattern of a drug in different age groups are mainly due to differences in—

a. Total body water (both intracellular and extracellular) — is much greater in infants

b. Fat content — is also higher in infants and elderly

c. Skeletal muscles — are lesser in infants and in elderly

d. Organ composition — the BBB is poorly developed in infants, the myelin content is low and cerebral blood flow is high, hence greater penetration of drugs in the brain

e. Plasma protein content — low albumin content in both infants and in elderly

Pregnancy

During pregnancy, the growth of uterus, placenta and foetus increases the volume available for distribution of drugs. The foetus represents a separate compartment in which a drug can distribute. The plasma and the ECF volume also increase but there is a fall in albumin content.

Obesity

In obese persons, the high adipose tissue content can take up a large fraction of lipophilic drugs despite the fact that perfusion through it is low. The high fatty acid levels in obese persons alter the binding characteristics of acidic drugs.

Diet

A diet high in fats will increase the free fatty acid levels in circulation thereby affecting binding of acidic drugs such as NSAIDs to albumin.

Disease States

A number of mechanisms may be involved in the alteration of drug distribution characteristics in disease states:

a. Altered albumin and other drug-binding protein concentration.

b. Altered or reduced perfusion to organs or tissues.

c. Altered tissue pH.

An interesting example of altered permeability of the physiologic barriers is that of BBB. In meningitis and encephalitis, the BBB becomes more permeable and thus polar antibiotics such as penicillin G and ampicillin which do not normally cross it, gain access to the brain. In a patient suffering from CCF, the perfusion rate to the entire body decreases affecting distribution of all drugs.

Drug Interactions

Drug interactions that affect distribution are mainly due to differences in plasma protein or tissue binding of drugs. This topic is discussed under the same heading in chapter 4.