Therapeutic Relevance : Providing answers

    The questions of How much? How often? How long?? and many more are answered by the drug's pharmacokinetic and pharmacodynamic studies. This will in turn result in better and safer use of drugs for treatment.

   

Empirical Approach in Designing Dosage Regimen

    Earlier the dosage regimen of drugs was established through trial and error by adjusting factors such as dose, dose interval etc and then observing its effects. With this a regimen can be set up but with excessive side effects and ineffective therapy. It also doesn't explain the apparent difference in regimes for different drugs, nor the principles underlying that leads to effective dosage of other drugs.

Rational Approach

    With advancement, its now understood that its the concentrations at the active site that drive the responses rather than the dose and to obtain and sustain the response, appropriate exposure-time profile of the drug within the body needs to be generated. This requires proper understanding of the factors that control this exposure profile.

The input-response relationship ( a.k.a. dose-response) has a pharmacokinetic and a pharmacodynamic phase.

1. Pharmacokinetic phase : covers relationship between drug input ( includes adjustable factors like- dose, dosage form, route and frequency of administration etc.) and the concentration achieved with time; i.e. in simple terms- how the body handles the drug.

2. Pharmacodynamic phase : covers relationship between concentration and effects ( both desired and adverse) produced with time; or simply, how the drug affects the body.

Therapeutic Window

Some basic ideas have helped to rationalise drug administration better. 

• The intensity of effects increases as exposure to drug increases, but only to a threshold value above which the response cant increase even with increase in exposure.

• Drugs act on different parts of the body and its effect produced varies from one another even if the measured response is same.

• Drugs can have multiple effects - be it desired or undesired. 

    So very low exposure lead to inadequate desired response and too high exposure can increase the adverse effects. There exists an optimal range of exposure between the extremes which is referred to as the therapeutic window in which desired therapeutic response without much adverse effects. Some drugs have very narrow therapeutic window and thus has a small margin of safety, while some others have wide ones.

Therapeutic Window