Diazepam PBPK model
The detailed description of the PBPK model used can be found in Gueorgueiva et al., 2006. Its schematic representation can be seen in the following figure. It consists of 11 compartments describing the concentration of the drug in various tissues, namely liver (LI), kidney (KI), brain (BR), intestine (IN), stomach (ST), muscle (MU), adipose (AD), skin (SK), gonads (GO), heart (HT) and lungs (LU), one compartment to model the rest of the body (RE) as well as two blood pools; venous (VEN) and arterial (ART). The parameters of the model are divided into drug-dependent and physiological (drug-independent) parameters. The first category comprises eleven tissue-to-plasma partition coefficients (K<sub>p</sub>), fraction unbound in plasma (fu), blood-to-plasma ratio (R), and intrinsic hepatic clearance (CL<sub>int</sub> , in L/h). The physiological parameters of the model are simply the regional tissue blood flows (Q) and tissue volumes (V).
