Appendix A.1. Clearance per unit mass of tissue and permeability surface area product
Clearance and many of the other constants are often stated per unit mass of tissue. Whether CL is being used to mean clearance from a named region, e.g. the brain, or clearance per unit mass is usually easy to determine from context. The units, e.g. cm3 s−1 or cm3 s−1 g−1 respectively, make it clear.
Expressing clearance per unit mass can be particularly convenient when the mechanism is efflux across the blood–brain barrier. For instance if a substance is cleared by passive transport across the barrier at a rate that is proportional to concentration, i.e. the efflux is Jefflux = Pc, where P is the permeability. The amount transferred per unit time out of unit mass of tissue is Jefflux × S = P × S × c where S is the surface area of the blood–brain barrier per unit mass of tissue. Because the amount transferred brain-to-blood per unit mass is both P × S × c and CLBBB × c, where CLBBB is the clearance by efflux across the blood–brain barrier, CLBBB and the PS product are synonyms.
The PS product is usually measured for influx. If the transport mechanism is passive, then this is also the PS product for efflux. (For ions see the next section). Many instances of transport are not well-described using a single value of permeability. For instance if the transport process saturates, the permeability, calculated as observed flux from source to destination divided by source concentration, will decrease as the concentration increases. Results are sometimes reported in terms of permeabilities even when there is known to be an active component of the transport. This allows comparison of the fluxes via active and passive mechanisms, but otherwise permeability is not a good description of active transport. If permeability is to be used, it is necessary to allow the values of P to be different for influx and efflux.