DRUG KINETICS-PART-11-NONLINEAR DRUG KINETICSW

NONLINEAR OR EXPONENTIAL KINETICS

Non linear kinetics does not obey first order straight line kinetics on increase in dosages.It is the kinetics that follows after the drug is saturated in some enzymatic or carrier mediated system inside the body on increasing in dosage.In other words,the body will not move the drug immediately after administration until the drug is saturated in some system of the body.Hence this kinetics does not follow a straight line first order plot in a graph rather it follows a curved line in a graph plotted the plasma concentration values on y-axis against the time interval of the dosage on the x-axis.

1.The Area Under the Curve (AUC) does not follow the dose

2.The drug excreted does not proportional to the drug administered.

3.High doses may promote the elimination half life.

4.Increase in dosage may change the ratio of the metabolites formed.

These are the characteristics of the non linear drug kinetics.

The non linear drug kinetics are mathematically described by the following velocity reactions devised by Michalis-Menten Equation.

                     -dCp/dt  = VmaxCp/kM+Cp

where Vmax is the maximum velocity of the reaction,Cp is the sustrate or plasma drug concentration,and kM is the rate contant equals to the Cp at 0.5 Vmax.

At low C p values where kM >> Cp this equation becomes a first order kinetics because both kM and Vmax are constants.

              -dCp/dt = Vmax Cp/km =k'Cp 

At high Cp values where Cp >> kM the equation reduces to a zero order kinetic equation as follows.

                -dCp /dt   = Vmax

From the above illustration it is observed that drugs that follows non linear kinetics may show zero order elimination at high concentration ,a mix of zero-first order kinetics at intermediate concentration and a first order kinetics at low concentration.