Pharmacokinetics in the older patient

The medicines management of an older patient is complicated by factors such as multiple diseases, complex medication regimes and the ageing process^[1]. Safely administering medication to an older patient is a significant and critical challenge when ensuring patient care.

In general drug absorption, distribution in the body, activity, metabolism and excretion can all change as a result of ageing. An older patient is more likely to experience side effects as well as experiencing difficulty in swallowing their medication.^[1]

A survey reported that 68% of patients responded to the issue of swallowing medication by crushing tablets or opening capsules.^[2] Any change, like crushing tablets, can alter the absorption characteristics. This may result in changes in the drug pharmacokinetics and bioavailability which can impact on efficacy and safety.^[3]

Drug absorption

Tablets or capsules are designed to allow the release of a drug over a time period into the blood. If the stomach is full or empty, this may affect the speed at which absorption occurs and the amount of drug which is absorbed.^[1]

Numerous gastrointestinal changes occur as part of the ageing process, however this doesn’t appear to have a significant impact on drug absorption.

The effect of polypharmacy should be considered and monitored in older patients. It is important to recognise the impact that co-prescribed drugs may have on drug absorption. Non-adherence rates (43-100%) with drugs in older patients have been associated with complicated medication regimens and polypharmacy.^[4]

Drug distribution

Once a drug is absorbed it’s carried around the body in the blood stream, distribution is the term used to describe the movement of the drug into body tissues. The extent and pattern of distribution will be dependent mainly on the plasma and tissue protein binding characteristics of the drug and its solubility in fatty tissues.^[1]

Drug distribution is affected by the changes in body composition associated with age due to an increase in body fat percentage and decrease in lean muscle mass.

Drug metabolism

Drug metabolism is the process by which the body chemically breaks down or changes a drug allowing for the eventual elimination from the body. Most metabolism takes place in the liver, although it can occur in other areas of the body such as the intestines. Drugs which are metabolised quickly have a short duration of action and need to be administered more frequently, whereas those which are metabolised more slowly will need administration less often. In general, as drugs are metabolised their therapeutic effect diminishes.^[1]

Liver metabolism

Several age-related changes are known to influence liver function. These include:

• Reduction in total liver size
• Reduction in liver blood flow (up to 58% reduction between 25 and 65 years of age)

The reduction in total liver size would be expected to result in a decrease in the levels of drug metabolising enzymes. A further decrease in efficiency would be expected to result from the reduction in liver blood flow as this would result in a decrease of exposure of the drug to metabolising enzymes.^[1]

Liver enzymes – inducers and inhibitors

Certain drugs cause induction of liver enzymes resulting in faster metabolism of some other drugs, whilst drugs called enzyme inhibitors reduce the action of the liver enzymes resulting in slower metabolism of other drugs. This effect is of importance when one of these enzyme affecting drugs is started, stopped or the dose changed, and is especially important in older patients who may be on several medications at any one time.^[1]

Drug elimination

Once drugs have had their desired effect, they need to be eliminated by the body. Excretion predominantly occurs via renal elimination in the kidneys.^[1]

Renal Excretion

The total size of the kidneys decreases with age, as does the number of functioning nephrons. There is also decreased renal blood flow with increasing age.^[1] Ageing is also accompanied by a reduction in both glomerular function and tubular function. It has been suggested that by the age of 70, there may be a 30-40% reduction in glomerular filtration rate. Renal function may also be affected by the presence of a coexisting disease, which is common in the elderly.

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ROS000057-003 Aug 2023