Predicting Drug Distribution Characteristics Using the Simcyp Simulator

The Simcyp® Simulator allows the prediction of drug distribution characteristics at several levels, including

  • Prediction of Vss from drug lipophilicity and plasma protein binding data
  • Prediction of drug concentration-time profiles in blood and tissues based on a full physiologically-based pharmacokinetic (PBPK) model

The Simcyp Simulator estimates the variability in the volume of distribution of a compound in a population. The minimal PBPK distribution model allows for a single-adjusting compartment (SAC). The full PBPK model allows users to select and replace a perfusion-limited organ with a permeability-limited organ and/or to define an additional organ (which can be permeability- or perfusion-limited).

Incorporation of transporter effects

The physiologically-based pharmacokinetic models within the Simcyp Simulator can accommodate the effects of saturable influx and efflux transporters in the intestine, liver and brain. In addition, users can investigate drug-drug interactions involving transporters. The Simcyp Simulator includes the following transporters: P-gp, BCRP and MRP2 in both the gut and liver; OATP1B1, OATP1B3, OCT1 and MRP3 in the liver and P-gp, BRCP and MRP4 in the brain. Users can also define their own influx transporter to simulate the effects of drug uptake in the intestine.

Blood-brain barrier

The Simcyp Simulator’s full-PBPK model includes a permeability-limited, four-compartment brain model for both a substrate and a main inhibitor. It enables simulating drug disposition in the central nervous system (CNS) by taking account of the transporters at the blood-brain-barrier (BBB) and blood-cerebrospinal-fluid-barrier (BCSFB). This feature can provide insights into the efficacy and safety of CNS drugs. Estimated concentrations of a drug in each brain segment can also be used to assess pharmacodynamic effects.

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