Theoretical Pharmacokinetics

Information about the time course of drug absorption, distribution and elimination
(pharmacokinetics) can be expressed in mathematical terms and has contributed to our
understanding and planning of drug regimens. Pharmacokinetic principles aid in the selection
and adjustment of drug-dose schedules.
Half life:
Half life (t1/2) of a drug is the time taken for the concentration of drug in the blood or plasma to
decline to half of original value or the amount of drug in the body to be reduced by 50%. It has
two phases i.e half-life of distribution and half-life of elimination.
A half-life value can be readily determined for most drugs by administering a dose of the drug to
a subject, taking blood samples at various time intervals and then assaying the samples., For
example if a blood level of drug A is 8.6 mg/ml at 10 minutes and 4.3 mg/ml at 60 minutes, so
the half – life of that drug is 50 minutes.
In most of the cases the rate of disappearance of a drug from the body is reflected in the rate of
lowering of its plasma concentration following a single intravenous dose, the plasma
concentration of the drug is focused to fall exponentially. With drugs whose elimination is
exponential, the biological half – life is independent of the dose, the route of administration and
the plasma concentration. It depends on VD as well as on the metabolism and renal excretion of
the drug.

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.
Concentration
mg/L Intravenous
Oral

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.