Selenium is a possible cancer preventive agent, and is being considered for use in intervention trials. A study in collaboration with the Cancer Prevention Studies Branch (Z01 CN 00101-09 CPSB) is in progress which will provide information on the pharmacokinetics of selenium in its prototype forms -- sodium selenite (inorganic form) and selenomethionine (organic form). This information is unavailable for these agents in the dose currently considered optimal, and is necessary to the determination of time and manner of administration. Parameters such as percent absorption, maximum concentration, time to maximum concentration, and mean residence times will be estimated for a single dose and compared in fasting and non- fasting subjects. Integrated kinetic models are being used to interpret the study data more fully. Such models are useful in making inferences about drug metabolism and about the distribution of the drug in various body pools. Models of selenite and selenomethionine have been developed. Various body pools have been hypothesized and rates of exchange between them estimated, as well as mean residence times. Comparisons of rate constants for subjects when fasting and when non-fasting suggests that fasting status modulates the appearance of selenite in the plasma and that there is a greater first pass effect when the dose is given with food. The models indicate important kinetic differences between selenite and the selenomethionine, with selenium from selenomethionine better absorbed and retained, and reutilized. An analysis of variations in total selenium levels in the plasma, urine and feces indicates high levels of within-subject variability, especially in urine and fecal samples, suggesting plasma levels are preferable, with multiple measures to enhance precision when determining selenium status.
