Domain of validity of the double isotope tracer method for measuring fractional zinc absorption: theoretical justification

Several approaches for estimation of fractional zinc absorption (FZA) by calculating the ratio of oral to intravenous stable isotopic tracer concentrations (at an appropriate time) in urine or plasma after their simultaneous administration have been proposed in the last decade. These simple-to-implement approaches, often referred to as the double isotopic tracer ratio (DITR) method, are more attractive than the classical "deconvolution" method and the more commonly used single-tracer methods based on fecal monitoring and indicator dilution, after oral or intravenous tracer administration, respectively. However, the domain of validity of DITR for measuring FZA has recently been questioned. In this paper, we provide a theoretical justification of the validity of four different "approximate" formulations of the DITR technique by demonstrating mathematically that their accuracy is a consequence of the particular properties of zinc kinetics.