Figure 19.

Partly flow-partly compartmental model of drug influx and efflux at the BBB and drug binding to plasma proteins and brain tissue proteins. (A) Drug in plasma may be bound to a plasma globulin, such as α₁-acid glycoprotein (AAG), which is GL° and GL in the arterial and capillary compartments, respectively, or bound to albumin, which is AL° and AL, or may be free, which is L_F° or L_F, in the arterial and capillary compartments, respectively. The free drug in brain is L_M, and the tissue bound drug in brain is PL. The rate constant of drug metabolism is K_met. The rate constants of drug dissociation with AAG, albumin, and the tissue binding protein are K₁, K₇, and K₆, respectively. The products of the rate constants of drug association and the concentration of the respective protein are given by K₂, K₈, and K₅, respectively, for AAG, albumin, and the tissue binding protein. The rate constants of drug influx and efflux across the BBB are K₃ and K₄, respectively. The brain capillary transit time is denoted as $\overline{t}$. (B) Model predictions for testosterone concentrations in plasma and brain pools shown in (A). Model simulation is based on plasma sex hormone binding globulin and albumin concentrations of 28 nM and 640 μM, respectively. Reproduced with permission from [1096], Copyright© 1985 American Physiological Society.