The term pharmacokinetics relates to what the body does to drugs as they move in, through and out of the body. This includes absorption, distribution, metabolism and excretion, which together determine the onset, duration and intensity of action of the drug. Pharmacokinetics can change as a person gets older.

Absorption

Changes are not usually clinically significant.

Distribution

With age, changes in body composition have a significant impact on drug distribution. Water-soluble drugs have a reduced volume of distribution and achieve higher blood levels. Prescribers should therefore reduce doses to minimise toxicity. Lipid-soluble drugs concentrate in the brain and fatty adipose tissue.

As clearance from adipose tissue is relatively slow, it can cause excessive sedation. Circulating proteins may decrease in older age, displacing medicines that are highly plasma protein bound and causing greater toxicity.

Metabolism

Many drugs are metabolised by the liver, so a reduction in liver function affects their removal from the body. Ageing can contribute to the liver reducing in size and blood flow, causing drug delivery and clearance to lessen. Drugs with a high hepatic extraction ratio reach higher blood levels when blood flow to the liver is reduced.

While ageing affects liver efficiency, overall metabolism is normally only slightly impaired. Liver function is difficult to measure as tests indicate damage, not metabolic effectiveness. Age-related changes vary and are hard to predict. The British National Formulary offers guidance on dose modifications for patients with liver impairment.

Excretion

Excretion is the most significant age-related pharmacokinetic change, and is both predictable and measureable. Reduction in renal function affects the pharmacology of many drugs. Failure to excrete medicines causes accumulation and toxicity.

Drugs can accumulate slowly and signs of toxicity may not appear until days or weeks after taking the drug. Some drugs also become ineffective with reduced renal function. When prescribing for older people, reduced renal function must be considered, as well as the potential for further damage to already impaired kidneys from nephrotoxic drugs.

Such drugs should be administered with caution, starting at a low dose and titrating up to the desired response. The expected benefits should outweigh the risks of the least nephrotoxic drug at the lowest effective dose.