Lauren Olsen, a GP trainee at a practice to which David Spencer provides prescribing advice, contacts David to discuss an issue that has been concerning her.

“David,” she says, “these days we’re always encouraging our patients to take lifestyle measures to improve or maintain their general health, and I’ve been quite impressed by how many are taking the advice seriously and implementing it.

“A lot of them have taken up regular exercise, like running, swimming or using a gym, and that’s great because it obviously brings physiological benefits. But, particularly in the case of people on long-term medication, I wonder whether exercise might affect the effectiveness of their drugs?”

“I think I can give you some pointers there,” replies David.

Questions

1. What are the four processes involved in the pharmacokinetics of a drug’s activity?
2. What is the additional factor connected with exercise?
3. What is the effect of exercise on drug pharmacokinetics, and for which drugs has an effect been shown?

Answers

1. Absorption, distribution, metabolism, excretion.

2. Blood flow: At rest, the liver and kidneys – where much of drug metabolism and excretion take place – receive about 50 per cent of the body’s blood flow. During moderate-to-intense physical activity, blood is redirected from central organs (except the heart) to working muscles and, as a result, only 3 per cent of the body’s blood is distributed to the liver and kidneys. In addition, exercise decreases glomerular filtration rates in the kidneys by as much as 30 per cent and can take more than an hour to return to normal afterwards. It is therefore advisable not to take medication immediately before moderate-to-intense exercise.

3. Drug absorption can occur in subcutaneous and transdermal tissues; redistribution of blood flow to these sites during exercise can affect drug absorption. The rate of absorption of insulin increases significantly after subcutaneous injections into working muscles, and low plasma glucose levels have been reported as a result of the rapid absorption of insulin when injected into a muscle that is about to be actively worked. Exercising with a transdermal patch such as nitroglycerin or nicotine has also produced increased plasma drug concentrations.

Exercise has been shown to change drug binding to plasma proteins and other tissues, increasing during exercise, and this in turn may influence drug binding to plasma proteins and tissues. In addition, alterations in drug distribution may occur because of redistribution of blood to active muscles. Drugs shown to be affected in this way include theophylline and acebutolol. Digoxin binding has also been shown to be altered during exercise.

Improved fitness can alter metabolic enzyme activity and therefore affect drugs whose metabolism depends on this mechanism, although to date there is little evidence of clinical effect.