Low Clearance Assay For Intrinsic Clearance

in vitro assay to determine the intrinsic clearance of slowly metabolised compounds via human Hurel micro livers using low clearance assays

Poster Authors:

¹Katherine Fenner, ¹Ed Harrison,¹ Kritika Sadh and ²Barry Jones

¹ Pharmaron, West Hill Innovation Park, Hertford Road, Hoddesdon, Hertfordshire, EN11 9FH, United Kingdom

² Pharmaron, Pegasus Way, Crown Business Park, Rushden, Northamptonshire, NN10 6ER, United Kingdom

Low Clearance Assay for Predicting Human In Vivo Clearance

A low clearance Cl_inthigh-throughput assay using HUREL Micro Livers (Visikol) was designed to efficiently predict in vivo clearance of slowly metabolized compounds. Low clearance is essential for successful drug discovery outcomes. However, it raises challenges to determine the metabolic clearance in vitro to enable the prediction of human pharmacokinetics.

In this poster, you can find out more about:

The in vitro methodology applied to determine the in vitro clearance of slowly metabolized compounds in HUREL micro-livers
Determination of fraction unbound in the incubation (Fu_inc)
Calibration of the clearance assay to enable the prediction of in vivo human clearance by determining a regression offset
Comparison of predicted unbound Cl_int values with values derived from literature data, showing predictions within 2-fold

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