Predicting human hepatic clearance from in vitro drug metabolism and transport data: a scientific and pharmaceutical perspective for assessing drug–drug interactions

Membrane transporters and metabolism are major determinants of the hepatobiliary elimination of drugs. This work investigates several key questions for drug development. Such questions include which drugs demonstrate transporter‐based clearance in the clinic, and which in vitro methods are most suitable for drug classification, i.e. transporter‐ vs metabolism‐dependent compound class categories. Additional questions posed are: what is the expected quantitative change in exposure in the presence of a transporter‐ and/or metabolism‐inhibiting drug, and which criteria should trigger follow‐up clinical drug–drug interaction studies.

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