Order Of Kinetics

FIRST ORDER KINETICS:

• Absorption, distribution, biotransformation and excretion processes are mostly occurring at rates proportional to plasma drug concentration.
• 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 drug in body is eliminated per unit time.
• Rate of elimination is proportional to amount of drug in body.
• For drugs with first order kinetics time required to achieve steady state levels can be predicted from half life. 
• The majority of drugs are eliminated in this way.

FIRST ORDER METABOLISM:

• A drug may be given in doses that produce blood concentrations less than Km of enyzme for drug.
• v = Vmax  [C]
• Km + [C]
• When     Km >>> [C],
• then      v = Vmax [C]  &  v σ [C]   
• Km
• Rate of elimination is directly proportional to drug concentration.
• A constant fraction of remaining drug is metabolized per unit time. 
• Most drugs are given at concentrations smaller than Km of enzymes of their metabolism.

• A constant amount of drug is eliminated per unit time.
• Supply of enzymes are limited in body.
• So, with increasing dose enzymes gets saturated at a particular stage.
• At this point there is,
• No elimination.
• Constant biotransformation.excretion.
• So, rate of processes or reaction is not proportional to conc. or dose.
• Processes also referred as “Rate limited/zero order/saturation kinetics/clinically called “Non-linear kinetics”.

Eg:

• All enzyme mediated processes.
• Drugs involved: Aspirin, ethanol, phenytoin ,propanolol, tolbutamide etc. 

ZERO ORDER METABOLISM:

• A drug may be given in doses that produce blood concentrations greater than Km of enyzme for drug.

• v = Vmax  [C]

• K m + [C]

• When   [C]  >>> Km,

• then     v = Vmax [C]  ,   and      v = Vmax

• [C] 

  A constant amount of remaining drug is metabolized per unit time. 

  Phenytoin undergoes zero order metabolism at doses given.

Drugs showing zero/pseudo-zero order kinetics :

• Phenytoin
• Theophylline
• Alcohol
• Tolbutamide
• Warfarin 
• Salicylates (Aspirin)
• Propanolol