DRUG KINETICS-PART-6

HOW THE BODY MOVES DRUGS

In this post we see how the body moves the drug administered by,

Intravenous Infusion:-

When a drug is administered through continous intravenous drip the body absorb it by a zero order process that means the absorption is constant at a given time independent of the initial concentration or the concentration available for absorption followed by the elimination in a first order process that means the elimination occurs with a direct proportion to the available concentration.

Similarly a few oral controlled release tablets also follows a zero order absorption and first order elimination by the body.

The plasma concentration Cp at any time after the start of the I.V. infusion can be calculated by the following equation,

                     Cp  = [R/VDk ](1-e to the power -kt)

R-the zero order rate of infusion given in units as milligrams per constant time.

If the infusion stopped then the Cp decreases with the first order elimination.

k-the elimination half life can be calculated from the slope by plotting the declining Cp value against time.

As the infusion is continued the Cp increases to a plateau which is known as the plasma steady state concentration abbreviated by Css.

At the steady state concentration the rate of absorption equals to the rate of elimination.

                 Css  = R/VDk

and the rate of infusion can be calculated by the rearrangement of the above equation by the desired known values of Css,VD and k as follows'

                     R = Css *VD k.

where Css is the target desired concentration and the product of VDk is equals to total clearance ClT.

A loading dose DL is the initial I.V.bolus injection to attain the Css as quicly as possible.Once the point of steady state is reached we can start the infusion.

The time to reach Css depends on the elimination half life of the drug.

To reach a 99% of Css without dosing a DL it takes a time of 6.65 half life.

Hence DL is necessary to reach the Css quickly.

The DL can be calculated as follows.

          DL =Css * VD   or  R/k

For a highly toxic drug with a narrow therapeutic window an I.V.drip provides a relatively constant plasma concentration which should not be more than the Minimum Toxic Concentration(MTC) and shold not be less than the Minimum Effective Concentration(MEC).