When does the rate-determining step in the hepatic clearance of a drug switch from sinusoidal uptake to all hepatobiliary clearances? Implications for predicting drug-drug interactions

Data Supplement

• Supplemental Data -

  Methods

  Supplementary Table 1 - Applying the RDS framework to drugs with published in vitro hepatobiliary clearances
  

  Supplementary Figure 1 - Irrespective of the CLs in value, the systemic AUC of a drug is determined by the CLmet+bile/CLsef ratio and not the magnitude of the CLmet+bile and CLsef clearance
  

  Supplementary Figure 2 - The tipping point depends on the AUCR cutoff chosen to represent a significant DDI
  

  Supplementary Figure 3 - Impact of CLsin underprediction on the tipping point
  

  Supplementary Figure 4 - Underprediction of hepatobiliary clearances impacts DDI liability predictions
  

  References