Students often find pharmacokinetics difficult. Two of the reasons are that a very formal writing style together with many equations make the subject appear much more difficult than it is. In this chapter we have deliberately adopted an informal style and aimed to keep key concepts as simple as possible. We hope we have succeeded and that you will find the chapter helpful as you prepare to become good prescribers.

Why is, amoxycillin administered three times daily, cotrimoxazole twice and phenobarbitone only as a single daily doses? Why was a slow-release theophylline preparation developed and why may it be taken only once a day? Why do we often give analgesics as a single dose but antibiotics as a course of doses, which should be taken regularly for a period of days?

If you could design it, what would an ‘ideal’ drug do, and how would it behave? Perhaps this depends on what it is being used for. If it is to treat a chronic condition such as high systemic blood pressure then it should be easy to take, not require injection, and should reduce the blood pressure to the normal range and maintain it there without causing adverse effects. If it were hardly metabolized in, or lost from, the body in any way it might be possible to give a single dose and maintain the effect for a very long time – weeks or even months – good for the patient but not so good for the manufacturer who wants to sell lots of his drug! What about a drug for headache? It needs to be easy to take, to act quickly, but it does not need to stay around in the body for a long period once the headache is relieved, and indeed, this could be a disadvantage if the drug produces unwanted or adverse effects. So it needs characteristics different from those of a drug to treat hypertension which ideally requires a long duration of effect.

In the past before clinical pharmacokinetics (literally – “movement of drugs” – implying measurement of the rate of movement of drugs into, out of, and around the body compartments) had been established in the 1970s, dosage regimens were decided largely by trial and error, relying on measurement of the therapeutic effect to tell you when a response had occurred and the appearance of toxic effects to tell you when you had given too much. The ability to measure drug concentrations in body fluids meant a more precise way existed for deciding by what route and how frequently drugs needed to be given to get the best outcome for the patient.

In this chapter we will look at the factors that are responsible for differences in the rate of onset, the duration and size, and the rate of offset – or loss – of a drug's effect.