Table 1.

Assumptions and considerations required when using the ratio of urinary excreted carbon‐14 after oral and intravenous administration to estimate fraction absorbed

Assumption	Reason
No metabolism in GI lumen with the metabolites absorbed and renally cleared.	This could yield an overestimate of F a because metabolites generated in the lumen would be included as absorbed drug.
No first pass intestinal enterocyte metabolism of drug with instantaneous secretion of metabolites into the lumen.	This could yield an underestimate of F a because some of the parent drug that was absorbed orally into enterocytes was metabolized and the metabolite secreted. (Thus, the estimate of F a is truly an estimate of the composite F a · F g).
No first pass intestinal enterocyte metabolism of drug coupled with first pass biliary secretion of these metabolites that are ultimately excreted in feces (and not reversibly converted back into parent drug in the lumen).	This could yield an underestimate of F a because some of the parent drug that was absorbed orally into enterocytes was metabolized and the metabolite was extracted by the liver and secreted in bile before reaching the kidney.
There is enough excretion of drug‐related material in the urine that reliable and accurate measurements of total urinary carbon‐14 can be obtained.	If 14C is very low in urine, variability could be greater and F a estimates will be less precise.

F _a, fraction absorbed; GI, gastrointestinal.