[Background] In general, oral bioavailability (F) and intestinal availability (FG, a ratio of drug escaping from intestinal metabolism during absorption) are calculated by comparing the clearances evaluated after intravenous and oral doses. Thus, an intravenous-dose study is necessary for their evaluations, and moreover, inter-individual and inter-study differences in the clearance may produce serious errors. In the previous study, we demonstrated that FG is evaluable from changes in the AUC and plasma half life (t1/2) associated with drug-drug interaction (DDI) for relatively well-absorbed substrate drugs of CYP3A4 when its inhibitor is co-administered1). In this study, the application of this method (DDI method) is extended to less absorbed drugs, and furthermore, to the evaluation of F. [Method] Basic equations of the DDI method (Scheme) were derived from the clearance theory. To evaluate FG and F in the DDI method, the absorption ratio (FA) needs to be approximated, but unnecessary to be very precise, hence it is named tentative FA in the scheme. Tentative FA was fixed previously1), but in this study, approximated statistically or by the membrane permeability determined in vitro experiments. It was assumed that FG becomes 1.0 when strong inhibitors are co-administered (FG*). Extensive Monte-Carlo simulations were conducted to check preciseness of the DDI method. Furthermore, FG and F of approximately 60 drugs (mainly substrates of CYP3A4) were evaluated based on literature information, and compared with the observed values if available. [Results and Discussion] The simulation study indicated that the modified DDI method provides reasonable estimation of FG using tentative FA approximated statistically even for poorly absorbed drugs (i.e. FA < 0.3). For evaluation of F, tentative FA needs to be more precise; accordingly approximated by in vitro information such as the permeability determined in the Caco-2 system. Overall, F and FG obtained by the DDI method were in excellent accord with those evaluated by other methods using the systematic clearance after intravenous dose (Figure). Since evaluation of a DDI is frequently carried out within a single study using the same subjects, it seemed that the DDI method provides more stable evaluation compared with the conventional methods in many situations. [Conclusion] The DDI method was proposed as a robust technique for evaluation of FG, and in addition, it may become an alternative method for evaluation of F when an intravenous-dose study is unavailable. Reference: 1) Tsukihashi et al., A new calculation method of intestinal availability from pharmacokinetic changes by drug-drug interaction, 25th JSSX Annual Meeting, 2010, Tokyo, Japan.