Mostafa. You can not achieve Css if you only give one dose. Css is the desired plasma concentration that is "maintained" for a particular period of time, usually in the span of 24 hours. In giving a single dose, e.g. APAP, you would only expect its peak plasma concentration at some point then elimination follows and no steady state occurs. If you want to achieve the desired Css faster (not anymore waiting for the 4-5 half-lives), that's when you give the loading dose. In this way, the desired Css will already be achieved on the 2nd and the succeeding doses.

Mostafa,

Note that Css is the steady state level that is reached after several half-lives following regular multiple dosing. The therapeutic level is simply the blood concentration that will result in a therapeutic response which (for certain drugs) can be reached just from a single dose.

Here's an example, maybe it's clearer this way:

Drug A (renally excreted) will cause effective pain relief at a plasma concentration of, say, 10ng/ml for two patients.

In one of the patients, otherwise healthy, the drug is administered once daily, resulting in a steady state concentration of 10ng/ml. Would you apply the same regimen to the other patient with kidney failure, therapeutic levels would be the same, however, the drug would accumulate, resulting in much higher plasma concentrations.

Also, css is not an absolute value, it depends on the repeated doses given, intervals etc. The therapeutic concentration however is (at least in a specific group of patients).

Thank you all!