Prediction of drug bioavailability in humans using immobilized artificial membrane phosphatidylcholine column chromatography and in vitro hepatic metabolic clearance

This study reports a rapid screening method for the prediction of oral drug bioavailability in humans based on combined immobilized artificial membrane (IAM) chromatographic capacity factor ( k IAM ) and in vitro stability in hepatic microsomes. The fraction of drug absorbed ( F a ) in humans was predicted for a set of 15 structurally diverse commercial drugs based on k IAM values using a mobile phase consisting of acetonitrile: Dulbecco's phosphate‐buffered saline. The hepatic intrinsic clearance ( CL   int ′ ) was calculated from in vitro disappearance half‐life, and the oral bioavailability was predicted using in vitro hepatic clearance ( CL h ) and F a . Significant correlations were observed for the relationships between predicted hepatic extraction ratios ( ER h ) and actual presystemic metabolism ( r = 0.854) and between predicted and observed oral bioavailabilities ( r = 0.805; p < 0.01). The IAM capacity factor together with the hepatic microsomal disappearance half‐life may be useful in identifying compounds with high oral absorption potential in early drug discovery processes. Copyright © 2009 John Wiley & Sons, Ltd.