order of kinetics

FIRST ORDER KINETICS:
  • Absorption, distribution, biotransformation and excretion processes are mostly occurring at rates proportional to the conc. of drug in the plasma
  • A constant fraction of drug is absorbed, distributed, biotransformed and excreted per unit time
  • These processes increase in rate with increase in conc. and decrease with falling conc.
  • A constant fraction of the drug in the body is eliminated per unit time
  • The rate of elimination is proportional to the amount of drug in the body
  • The majority of drugs are eliminated in this way
  • For drugs with first order kinetics the time required to achieve steady state levels can be predicted from Half life 


Half life

  • Elimination
1t1/2 50%
2t1/2
75%
3 t1/2
87.5%
4 t1/2 93.75%
5 t1/2 96.875
FIRST ORDER METABOLISM:
  • A drug may be given in doses that produce blood concentrations less than the Km of the enyzme for the drug.
  • v = Vmax [C]
  • Km + [C]
  • When Km >>> [C],
  • then v = Vmax [C] & v σ [C]
  • Km
  • Metabolism of the drug is a first order process.
  • Rate of elimination is directly proportional to drug concentration
  • A constant fraction of the remaining drug is metabolized per unit time.
  • Most drugs are given at concentrations smaller than the Km of the enzymes of their metabolism.
ZERO ORDER KINETICS:
  • A constant amount of drug is eliminated per unit time
  • Supply of enzymes are limited in the body
  • So, with increasing dose a time will come when the supply of enzymes get saturated
  • At this point no elimination occur
  • Biotransformation or excretion remains constant at this point
  • So, rate of processes or reaction is not proportional to the conc. or dose
  • Processes showing such kinetics are known as – Rate limited or zero order or saturation kinetics
  • Some times clinically called non-linear kinetics
  • All enzyme mediated processes show this type of kinetics
  • Passive diffusion like processes do not show this type of kinetics
  • e.g. aspirin, ethanol, phenytoin ,propanolol, tolbutamide etc.

ZERO ORDER METABOLISM:
  • A drug may be given in doses that produce blood concentrations greater than the Km of the enyzme for the drug.
v = Vmax [C]
K m + [C]v
When [C] >>> Km,
then v = Vmax [C] , and v = Vmax
[C]
  • Metabolism of the drug is a zero order process.
  • A constant amount of the remaining drug is metabolized per unit time.
  • Phenytoin undergoes zero order metabolism at the doses given.
Drugs showing zero/pseudo-zero order kinetics :
  • Phenytoin
  • Theophylline
  • Alcohol
  • Tolbutamide
  • Warfarin
  • Salicylates (Aspirin)
  • Propanolol

First Order Kinetics Zero Order Kinetics (Non linear Kinetics)

  • Constant fraction of drug is eliminated per unit time
  • Rate of elimination is proportional to plasma concentration
  • Clearance remains constant
  • Half life remains constant
  • Most of the drugs follow first order kinetics

  • Constant amount of the drug is eliminated per unit time.
  • Rate of elimination is independent of plasma concentration
  • Clearance is more at low concentrations and less at high,concentrations
  • Half life is less at low concentrations and more at high concentrations
  • Very few drugs follow pure zero order kinetics e.g. alcohol
  • Any drug at high concentration (when metabolic or elimination pathway is saturated)
  • may show zero order kinetics
Exam Question
  • Zero order kinetics is independent of Plasma concentration
  • Zero order kinetics occur in Phenytoin,Tolbutamide, Propranolol and Ethanol at high dose
  • In first order kinetics a constant proportion of plasma concentration is eliminated
  • In first order kinetics Rate of elimination is directly proportional to drug concentration
  • Zero order kinetics is otherwise known as saturation kinetics
  • In first order kinetics Clearance is constant
  • Elimination after 4 half lives in first order Kinetics is 93%
  • Elimination after 3 half lives in first order kinetics is 87.5%
  • For drugs with first order kinetics the time required to achieve steady state levels can be predicted from Half life
  • First order kinetics is Elimination of the drug is proportional to the serum concentration
  • In Zero order kinetics Constant amount of drug eliminated per unit time
Don't Forget to Solve all the previous Year Question asked on order of kinetics