According to the principles of the influence on biodistribution, pharmacodynamics and metabolism of drugs, three main methods of prolongation: (technological (pharmaceutical), chemical and physiological are distinguished.
Action of a drug may be prolonged to
1. Reduce the frequency of administration
2. Avoid large fluctuations in plasma concentration
3. Maintain drug effect overnight without disturbing sleep.
This can be achieved by
1. Delaying absorption – It is desirable to delay absorption, either to reduce the systemic actions of drugs that are being used to produce a local effect or to prolong systemic action.
2. By increasing the plasma protein binding – Congeners have been prepared which are highly bound to plasma protein and are slowly released in the free active form to have a prolonged duration of action like sulphamehtoxypyridaiazine.
3. By reducing the rate of metabolism – Small chemical modifications may markedly affect the rate of metabolism without affecting the biological action.
4. By reducing renal excretion -Tubular secretion of drug being an active process, it can be suppressed by a competing substance. Example – Probenicid prolongs the duration of action of penicillin and ampicillin.