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Mixed Order Kinetic



  • Is seen when the elimination process is not saturated.

  • With increasing plasma concentration, the rate of elimination increases.

  • Is seen when the elimination process is saturated.

  • The rate of elimination is at its maximum and it does not increase with increasing plasma concentration.

Mixed Order Kinetic
  • Is seen when the elimination process is saturated over the therapeutic concentration of the drug.

  • The elimination kinetic switches between first-order and zero-order kinetic.

At lower concentrations

↓

the elimination process is not saturated yet

↓

the drug follows first-order kinetic

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with increasing concentration → rate of elimination increases

↓

as the concentration of the drug increases further

↓

elimination process gets saturated

↓

kinetic switches from first order to zero order

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rate of elimination reaches the maximum and it does not increase with plasma concentration

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as the concentration of drug falls

↓

kinetic switches from zero order to first order

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thus kinetic switches between first and zero order depending on the concentration of the drug


  • Its also called:

    • Saturable kinetic

    • Capacity limited kinetic

    • Nonlinear kinetic

    • Michaelis Menten elimination kinetic

  • Examples of drugs showing mixed order kinetic:

    • Phenytoin

    • Digoxin

    • Warfarin

Problem with Mixed-Order Kinetic
  • It produces an unpredictable pharmacokinetic state. e.g. plasma half-life changes with dose.

  • May produce toxicity.

Once the elimination process is saturated

↓

a small increase in the dose

↓

result in a marked increase in concentration

↓

may produce toxicity

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therapy with such drugs should be carefully monitored.

 

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