Prediction of drug bioavailability in humans using immobilized artificial membrane phosphatidylcholine column chromatography and in vitro hepatic metabolic clearance
✍ Scribed by Beom Soo Shin; Chi Ho Yoon; Joseph P. Balthasar; Bu Young Choi; Seok Hyun Hong; Hyoung Jun Kim; Jong Bong Lee; Sang Wook Hwang; Sun Dong Yoo
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 487 KB
- Volume
- 23
- Category
- Article
- ISSN
- 0269-3879
- DOI
- 10.1002/bmc.1182
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✦ Synopsis
Abstract
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
) 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.