ABSTRACT
A critical role of bioavailability (BA) and bioequivalence (BE) evaluations is in drug discovery and development of small-molecule therapeutic agents. The focus of evaluation is the performance of a new drug entity or comparative evaluation of more than one compound. BA assessment is based on PK parameters and constants obtained from quantitative analysis of blood or plasma concentration of active compound. The PK measurements of systemic exposure such as AUC or Cpmax and other parameters dene the BA and BE (Chen et al., 2001a,b). The factors discussed in Chapter 8 can inuence the absorption, and thus the bioavailability of a compound. Factors such as such as gastric emptying rate, small intestinal transit time, blood ow rate, intestinal and hepatic rst-pass effect, inux and efux proteins, physicochemical characteristics of the compound, formulation factors associated with dosage forms, factors that inuence drug dissolution (Amidon et al., 1995), and inactive ingredients can inuence the absorption and bioavailability of a compound. Furthermore, variation in splanchnic blood ow and biliary secretion may inuence the rst-pass effect. The magnitude of bile salts can affect the solubility of the lipophilic compounds (Fleisher et al., 1999; Karalis et al., 2008), species differences, intra-individual variability (McGilveray et al., 1990), and specic site-dependency of absorption, The presence of food in the GI tract (Olanoff et al., 1986; Gupta and Benet, 1990) or other compounds will always remain sources of variability in BA measurements (Grifn, 1981; Walter-Sack, 1987).
