Fig. 1

Physiologically based Pharmacokinetic model for estradiol in women. Distribution of estradiol between venous and arterial blood compartments and 16 tissue compartments is represented. The liver and gonads are represented as permeability-limited tissues, and all other compartments well mixed. Estradiol enters the model through synthesis into the gonads, oral dosing (p.o.) into the intestine, and intravenous dosing (i.v.) into the venous blood. Estradiol is removed from the model through extra-hepatic clearance (CLeh) from the kidney, and intrinsic clearance from the liver. Intrinsic clearance is modelled as either a single ODE (Clint), ODE-based model of liver metabolism (LiverODE), or a genome-scale metabolic network (GSMN) as described in text