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Simcyp allows you to extrapolate in vivo metabolic clearance from routine in vitro data generated during drug development using a variety of systems, including human liver microsomes (HLM), human intestinal microsomes (HIM), human hepatocytes (HHEP), recombinant cytochrome P450 and UGT enzymes (rCYP, rUGT), cytosolic or S9 tissue fractions.
The in vitro intrinsic clearance (CLint) of a compound can be determined either from the enzyme kinetic parameters Vmax and Km or, more simply, from the rate of metabolism at a single substrate concentration, provided it is much lower than the Km value.
In cases where in vitro kinetic data are lacking, the parameter estimation and retrograde modules can be used to derive these data from clinical pharmacokinetic inputs using a 'top-down' approach.
A unique feature of the Simcyp platform is that it allows the prediction of the dispersion of hepatic clearance in a population. To do this effectively requires values of several system-specific scaling factors and the application of in vitro correction factors.
This section outlines how Simcyp handles: