The study of absorption, distibution,metabolism,excretio of drug and their relationship to pharmacological response. In simple word ; what the body dose to the drug. Linear pharmacokinetics.In the pharmacokinetic parameter for drug would not change when difference dose or multiple dose of drug is given. Non linear pharmcokinetics-if any deviation cause linear pharmacokinetics called non linear, mixed, capacity – limited kinetics.

1. Non linear pharmacokinetics

2. PHARMACOKINETICS
The study of absorption, distibution,metabolism,excretio of drug
and their relationship to pharmacological response. In simple
word ; what the body dose to the drug. Linear
pharmacokinetics.In the pharmacokinetic parameter for drug
would not change when difference dose or multiple dose of drug
is given. Non linear pharmcokinetics-if any deviation cause linear
pharmacokinetics called non linear, mixed, capacity – limited
kinetics.

3. CAUSES Of NON LINEARITY
 Absorption
 Saturable transport - riboflavin
 Intestinal metabolism - prodrug
 Distribution
 Plasma protein binding - cefriaxone
 CSF transport – benzyl penicillin
 Tissue binding - prednisolone
 Cellular Uptake - methicillin
 Hepatic uptake – indocyanin green

4.  Metabolism
 Saturable metabolism – phynetoin
 Co-substrate depletion – acetaminophen
 plasma protein binding – prednisolone
 Elimination
 Glomerular filtration -
 Tubular secretion – penicilline G
 Tubular reabsorption – water soluble vitamin

5. AUC
DOSE

6. MICHAELIS-MENTEN KINETICS
Drug biotransformation ,renal tubular secretion,and biliary
secretion usually require enzyme or carrier systems. These
systems are relatively specific with respect to substrate and have
finite capacities(I.e., they are said to be capacity limited).
Frequently, the kinetics of these capacity-limited processes can be
described by the Michaelis Menten equation:

7. dc/dt – rate of decline of drug concentration with time .
Vmax - theoretical maximum rate of the process.
Km – michelis constant
C<<Km – under this stiuation ,the equation Km+C =km
-dC/dt=Vmax C/ Km
C>>Km- under this situation Km+C=C
-dC/dt=Vmax

8. -dC/dt
Km Concentration
Vmax

9. ESTIMATION OF Km AND Vmax
 The parameter of capacity limited processes like metabolism,
renal tubular secretion and excretion can be easily define by
assuming one compartment kinetics for the drug and that
elimination invovles only a single capacity limited process.
 The Km and Vmax can be assessed from the plasma conc .time data
collected after i.v bolus administration of drug with non linear
elimination.

10.  Rewritting equation –
dc/dt =Vmax c/Km+c
 Integration followed by conversation to log10
log C=logC0 + (c0 -c)/2.303Km –Vmax / 2.303Km
 The Equation describe the line-
LogC=logC<-
0 –Vmax /2.303Km

12. At low plasma concentrations are identical. By setting the right-hand
sides of these two equations equal to each other, the following
expression is obtained.

13. Km AND Vmax FROM STEADY STATE
1) Linear-Burke plot/klotz plot
1/DR= Km/Vmax.Css+1/Vmax
2) The third Graphical method oR Direct Linear Method:
DR= Vmax-Km/Css

14. 100
200
300
400
500
600
700
020406080 20 40
Dmax
KmCss
Dose

15. Km and Vmax can also be calculated numerically by setting up
simultaneous equation as shown below:
DR= V max Css.1/Km+Css.1
DR= V max Css.2/ Km+Css.2
Combination of the above two equation yields:
Km= DR2-DR1/(DR.1/Css.1)-(DR.2/Css.2)