Saturable First-Pass Metabolism: Dose-Dependent Bioavailability

Most textbook first-pass models assume hepatic clearance is a fixed number, but for a meaningful subset of real drugs the liver's CYP450 enzymes themselves saturate at clinically used oral doses. This simulator renders that capacity-limited kinetics in 3D: drug molecules flow from the portal vein through a liver-lobule enzyme lattice whose glow shows real-time fractional site occupancy, and are metabolized or allowed through with a probability driven live by the Michaelis-Menten intrinsic-clearance formula CLint(Cu) = Vmax/(Km+Cu) feeding the well-stirred extraction-ratio equation. Adjust the entering dose concentration, enzyme capacity, binding affinity and hepatic blood flow to watch oral bioavailability F rise nonlinearly as dose increases — the mechanism behind why some drugs cannot simply be dosed proportionally.