Epinephrine kinetics in humans: radiotracer methodology

The use of the plasma epinephrine (EPI) level as an index of adrenomedullary activity in humans is complicated by the rapid removal of EPI from plasma by many tissues. To determine whether the kinetics of distribution and metabolism of EPI could be best quantified using the isotope dilution method or a mathematical modeling technique, eight human subjects received a [3H]EPI infusion for 50-60 min. Analysis of the steady state arterialized plasma levels of EPI and [3H]EPI using the isotope dilution technique showed that the basal plasma EPI appearance rate is 0.87 +/- 0.11 nmol/m2.min, and the basal plasma EPI clearance rate is 1.63 +/- 0.14 L/min.m2. Mathematical modeling of the [3H]EPI levels revealed that a biexponential curve fit was superior to monoexponential and triexponential curve fits. A two-compartment model was the minimal compartment model that accurately described EPI kinetics. The basal plasma EPI appearance (0.82 +/- 0.16 nmol/m2.min) and EPI clearance (1.67 +/- 0.15 L/min.m2) rates that were estimated from this two-compartment model are similar to the results derived from the isotope dilution method. Mathematical modeling revealed a large extravascular mass of EPI. We conclude that the isotope dilution and mathematical modeling techniques similarly describe plasma EPI kinetics in humans. Kinetic analysis using mathematical modeling provides new insights into adrenomedullary function in humans.