Bioavailability oral screening tool

Pintore et al., 2003 van de Waterbeemd and Jones, 2003 Crowley and Martini, 2004 Thompson, 2005 Avdeef et al., 2007 Cheng et al., 2007 Liu et al., 2008 Nomeir et al., 2009). Oral bioavailability can be viewed as a combination of two factors absorption and first-pass metabolism. Indeed, Cheng et al. (Lau et al., 2004 Cheng et al., 2006 Li et al., 2007) described a novel high-throughput in vitro assay based on a hybrid system that involved a combination of an absorption screen as well as metabolism screen in one system this system was used to evaluate multiple test compounds and has the potential to be used as a discovery oral bioavailability screening tool in the future. 

The genesis of in silico oral bioavailability predictions can be traced back to Lip-inski s Rule of Five and others qualitative attempts to describe drug-like molecules [13-15]. These processes are useful primarily as a qualitative tool in the early stage library design and in the candidate selection. Despite its large number of falsepositive results, Lipinski s Rule of Five has come into wide use as a qualitative tool to help the chemist design bioavailable compounds. It was concluded that compounds are most likely to have poor absorption when the molecular weight is >500, the calculated octan-l-ol/water partition coefficient (c log P) is >5, the number of H-bond donors is >5, and the number of H-bond acceptors is >10. Computation of these properties is now available as an ADME (absorption, distribution, metabolism, excretion) screen in commercial software such as Tsar (from Accelrys). The rule-of-5 should be seen as a qualitative, rather than quantitative, predictor of absorption and permeability [16, 17]. 

This model uses in vitro data to estimate the oral bioavailability ranges of chemically diverse compounds in a range of species, and represents a potentially powerful tool when combined with high-throughput in vitro screening. 

Stoner CL, Cleton A, Johnson K, Oh D-M, Hallak H, Brodfuehrer J, Surendran N, Han H-K (2004) Integrated oral bioavailability projection using in vitro screening data as a selection tool in drug discovery. Int. J. Pharm. 269 241-249. 

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