Pharmacokinetic transfer functions and generalized clearances.

A generalized steady-state clearance coefficient is defined to relate drug or metabolite mass transfer rates into one area of the body (area II) to the constant drug concentration in another area (area I). It is demonstrated that this clearance coefficient may be used in the transient case to calculate total mass transfer into area II when the drug AUC in area I is known. This generalizes the well-known "clearance formula" CL = Ae/AUC to cases in which several compartments separate areas I and II, as well as to cases where distributed models are preferred. Several applications are discussed, including a noninvasive means of determining the fraction absorbed of topically administered drugs.