Dosing intervals average steady-state plasma concentration

Systemic clearance, which measures the ability of the body to eliminate a drug, determines the relationship between the dosage rate and the average steady-state plasma concentration. When multiple (fixed) doses of a drug are administered at a constant dosage interval (r) the average plasma concentration that will be attained at steady-state can be predicted ... 

In a normal subject, systemic clearance of a drug is constant and it is presumed to be independent of the dose administered and the route of administration therefore, it will not play any role in influencing the "average" steady-state concentration. The "average" steady-state plasma concentration will be influenced by the three remaining parameters the dose administered, the chosen dosing interval and the absolute bioavailability (F), when applicable. 

Because the area under the plasma drug concentration-time curve during a dosage interval at steady-state is equal to the total area under the curve after administering a single intravenous dose, the average plasma concentration at steady-state can be estimated from... 

Therefore, in this example, if the subsequent doses are administered at a 24 h interval (i.e. dosing interval equals one half life of the drug), the peak steady-state concentration, the trough steady-state concentration and the "average" steady-state concentration will be twice the corresponding plasma concentration for the first dose. Is it accurate to say that if the peak plasma concentration at steady state is twice the peak plasma concentration for the first dose then the dosing interval represents the half life of the drug ... 

It should be noted that the "average" plasma concentration, obtained by employing Eqs 11.15 or 11.17, is neither the arithmetic nor the geometric mean of maximum and minimum plasma concentrations at infinity. Rather, it is the plasma concentration at steady state, which, when multiplied by the dosing interval, is equal to the area under the plasma concentration-time curve (AUC)o (i.e. from f=0 to t r). 

Regardless of the route of drug administration, the "average" plasma concentration at steady state is influenced by the dose administered, the fraction of the administered dose that reaches the general circulation (for extravascular routes), the systemic clearance of the drug and the chosen dosing interval. 

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