Bioequivalence and Bioavailability Forum

Hi Miityri,

❝ As you can see capecitabine and 5-FU curves have 2 slopes. What is the reason of such curve shapes?

Capecitabine is partly excreted unchanged into the bile and known to undergo enterohepatic recirculation; such profiles are common.

Capecitabine → 5’-dFCR → 5’-dFUR → 5-FU → DHFU → FUPA → FBAL

Note that the primary metabolite 5’-dFCR does not show first-order elimination between 1–4 hours as well (concave semilog-plot). C_max of the secondary 5’-dFUR is actually due to the reabsorbed fraction. If you walk the metabolization-chain further ‘downstream’ peaks merge and are shifted to later times.

❝ fed condition or something else?

See above – but in fasting state you would see a shift of the second peak towards later times (emptying of the gall bladder triggered by food). However, administration after food is the labeled use of Xeloda.

❝ In our study we have similar results.

As expected. Nothing to worry about in BE (that’s the drug, not the formulation).