Order Of Kinetics

Drugs are used for the treatment of diseases but the modes of administration of drugs are different. For example atenolol is administered once daily where as paracetamol needs 3-4 times administration daily. Morphine is more effective in intramuscular route, and insulin is in subcutaneous route. The mode of administration is designed on the basis of absorption, distribution, metabolism and excretion (ADME) of drugs. Drugs usually follow two processes for their phamacokinetic behaviour in the body. These are first order and zero order process.

First order:

This is the most common process for many drugs. The rate at which absorption, distribution, metabolism and excretion occur are proportional to the concentration of drugs i.e. constant fraction of this drug in the body disappears in each equal interval of time.

Zero order kinetic:

It is independent of the amount of drug present at the particular sites of drug absorption or elimination. Few drugs follow this process e.g. ethanol, phenytoin. Here constant amount of the drug is eliminated in each equal interval of time. On repeated administration of drug after certain stage it goes on accumulating in the body and leads to toxic reactions.

Steady state plasma concentration:

When a drug dose is given repeatedly over a given period, a steady state is eventually reached, at which point the amount of drug absorbed is in equilibrium with that eliminated from the body.
Steady state is achieved after 4 to 5 half –lives for most of the drugs which follow first order kinetics. For example a drug with half life of 6 hours will be expected to be at steady state after more than 24 hours of administration. The pattern of drug accumulation during repeated administration of drug at intervals equal to its elimination half-life.

For some drugs, the effects are difficult to measure, toxicity and lack of efficacy are both potential dangers, and/or the therapeutic window is narrow. In these circumstances doses must be adjusted carefully to a desired steady- state concentration by giving loading and maintenance doses.
Loading dose: The loading dose is one or a series of doses that may be given at the onset of therapy with the aim of achieving the target concentration rapidly.
Maintenance dose: To maintain the chosen steady-state or target concentration, the rate of drug administration is adjusted such that the rate of input equals to rate of loss.