Absorption via extravascular administration
If a drug is given by any other route, it is considered extravascular and must therefore undergo absorption.
Absorption is a first order process. As more drug reaches the absorption site more is absorbed (by a constant fraction). However, as drug enters the circulation, it is also eliminated. At some point, the absolute amount of drug offered to the systemic circulation is diminishing (because most of it is now absorbed). This causes a flattening of the concentration time curve and it will reach maximum concentration called Cmax at time tmax.
At this point the rate at which the drug enters the
circulation is exactly the same as the rate at which it leaves the circulation through clearance and this is analogous to an intravenous infusion. It is also possible that not all of the drug reaches the systemic circulation (see bioavailability).
If the clearance is diminished by half and the absorption kinetics remain the same, the AUC doubles after all administration.
If the volume of distribution doubles, the half-live doubles, it takes longer to reach tmax and the maximum concentration (Cmax) is lower. However, the AUC of both curves is equal.