Differentiation of organ availability by sequential and simultaneous analyses: Intestinal conjugative metabolism impacts on intestinal availability in humans*

The impact of intestinal conjugative metabolism on oral bioavailability was assessed by sequential and simultaneous analyses of the reported data in humans. The data were retrieved from reports on drugs that are metabolized by sulfate conjugation, and the organ availabilities affecting oral bioavailability were differentiated. Sequential analysis gave the following results. The intestinal availability (Fg) of salbutamol was 0.700, whereas hepatic availability (Fh) and bioavailability (F) were 0.893 and 0.493, respectively. Fg of (+)‐terbutaline, (−)‐terbutaline, and (±)‐terbutaline was 0.128, 0.254, and 0.250, respectively. In contrast, Fh of (+)‐terbutaline, (−)‐terbutaline, and (±)‐terbutaline was 0.979, 0.971, and 0.946, respectively. Fg and Fh of ethynylestradiol were 0.536 and 0.780, respectively. Simultaneous analysis also gave similar results, although the sequential analysis overestimated the intestinal availability. These results indicate that intestinal sulfation metabolism has more impact on intestinal availability than on hepatic availability, resulting in low bioavailability in humans. © 2005 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:571-575, 2005