Variation in drug responses between individuals can be affected by ethnicity, age, gender, pregnancy, disease and drug interactions. Thus the practitioner must take these factors into account for effective and safe drug treatment. Advances in mapping individual genetic information have led to the concept of introducing individualizing drug therapy to best suit likely receptive patients (personalized medicine). (Rang & Dale’s Pharmacology, 8th edition, Chapter 11 provides an expansion on this topic which is condensed below).
Responses to some drugs (e.g. vaccines, oral contraceptives) are robust and predictable to allow standard dose calculations to be used. Other drugs (e.g. antihypertensives, anticoagulants) require individual monitoring to ensure efficacy is reached and safety concerns are managed or minimized.
Age, gender and origin
An individual’s metabolism of drugs will change several times with age. The expression pattern of drug-metabolizing enzymes is different in the foetus and in infants compared to adults. In particular, premature infants can be deficient in some enzymes compared to full-term infants; coupled with a still developing renal system, this means attention must be given to these babies in terms of their ability to metabolize and eliminate drugs.
However, as the child develops, his or her ability to metabolize (oxidize) many drugs is more rapid than in adults. The dosing regimen may reflect this increased activity, until children reach puberty and the rate of drug metabolism converges to that of an adult.
Aging then causes further changes in the absorption, distribution, metabolism and excretion (ADME) of drugs:
Chronic, complicated diseases sometimes require the use of multiple drug treatments, and the likelihood of drug interactions becomes more probable, and competition for cytochrome P450 isoforms is more pronounced.
Serum albumin concentration decreases, increasing the likelihood of saturable drug binding and increased availability of circulating free fraction of a drug.
Lean body mass decreases, leading to changes in the volume of distribution.
Liver weight decreases, and cytochrome P450 has a reduced capacity to oxidize drugs, therefore affecting metabolism and elimination to certain drugs.
The influence of gender has been explored to a lesser extent, with a few instances of variations in drug disposition reported.
Ethnicity is understood to affect drug metabolism. For example, population differences in the expression of P450 isoforms have been reported in Caucasian versus Asian populations, as well as the rate of drug acetylation.