Estimate unbound fraction of drugs
Principal component analysis (n=2)
ElasticNet: Linear regression
1159 drugs x 28 variables obtained by RDkit & Chemaxon.
fup = f( logP, logS, polarity, pKa, hlb, aromaticity ....) = f( PC1(36.5%), PC2(20.3%) ); PC1+PC2 accounts for 56.8% variance
Drug metabolism pathway visualized by escher git map.
Use linear optimization with constraints to estimate metabolic fluxes of drugs .
Combine FBA ( flux balance analysis) and PBPK to characterize drug metabolism in hepatocytes.
Variants of SLCO1B1, ABCG2, and ABCC2 etc. will cause variations on parameters related to drug absorption, cellular uptake and clearance.
SLCO family transporters: absorption, hepatocyte uptake
ABCG family transporter: biliary clearance, bile duct
CYP family enzymes: oxidative reactions (O2, NADPH)