Oral Absorption, Intestinal Metabolism and Human Oral Bioavailability

Most of the drugs that are available in the marketplace are administered via the oral route, which is a convenient and cost effective route of administration (Lipinski 1995; Lipinski 2000; Lipinski et al. 2001; Lipinski 2004; Abrahamsson and Lennernas 2005). Thus, oral bioavailability is one of the key considerations for discovery and development of a new chemical entity (NCE). It is well recognized that poor oral bioavailability is one of the major causes of therapeutic variability, associated with the variable drug exposure (Beierle et al. 1999; Bardelmeijer et al. 2000; Katsura and Inui 2003). This is particularly important for drugs with narrow therapeutic window or potential for resistance development such as antibiotics and cytotoxic drugs (Bardelmeijer et al. 2000). Hellriegel et al. reported a significant inverse relationship between the oral bioavailability of drugs from several therapeutic classes and the coefficient of inter-individual variability in their oral bioavailability (Hellriegel et al. 1996).