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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

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

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

as the concentration of drug falls

kinetic switches from zero order to first order

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

therapy with such drugs should be carefully monitored.

 

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