Plateau Principle

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Chapter: Essential pharmacology : Pharmacokinetics; Metabolism Excretion Of Drugs, Kinetics Of Elimination

When constant dose of a drug is repeated before the expiry of 4 t½, it would achieve higher peak concentration, because some remnant of the previous dose will be present in the body. This continues with every dose until progressively increasing rate of elimination (which increases with increase in concentration) balances the amount administered over the dose interval.


PLATEAU PRINCIPLE

 

When constant dose of a drug is repeated before the expiry of 4 t½, it would achieve higher peak concentration, because some remnant of the previous dose will be present in the body. This continues with every dose until progressively increasing rate of elimination (which increases with increase in concentration) balances the amount administered over the dose interval. Subsequently plasma concentration plateaus and fluctuates about an average steadystate level. This is known as the plateau principle of drug accumulation. Steadystate is reached in 4–5 half lives unless dose interval is very much longer than t½ (Fig. 3.6).

 


 

The amplitude of fluctuations in plasma concentration at steadystate depends on the dose interval relative to the t½, i.e. the difference between the maximum and minimum levels is less if smaller doses are repeated more frequently (dose rate remaining constant). Dose intervals are generally a compromise between what amplitude of fluctuations is clinically tolerated (loss of efficacy at troughs and side effects at peaks) and what frequency of dosing is convenient. However, if the dose rate is changed, a new average Cpss is attained over the next 4–5 half lives. When the drug is administered orally (absorption takes some time), average Cpss is approximately 1/3 of the way between the minimal and maximal levels in a dose interval.

 

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