# Order Of Kinetics

## 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.

 Half life Elimination 1 t1/2 50% 2 t1/2 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 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.
ZERO ORDER KINETICS:
• 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
 First Order 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 Zero Order Kinetics (Non linear Kinetics) Constant amount of 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 is otherwise known as saturation kinetics.
• In zero order kinetics constant amount of drug eliminated per unit time.
• 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.
• 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.
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