Norepinephrine Metabolism in Humans

The present study was undertaken to quantify more precisely and to begin to address the problem of heterogeneity of the kinetics of distribution and metabolism of norepinephrine (NE) in humans, by using compartmental analysis. Steadystate NE specific activity in arterialized plasma during I3HINE infusion and postinfusion plasma disappearance of [3HINE were measured in eight healthy subjects in the supine and upright positions. Two exponentials were clearly identified in the plasma [HJNE disappearance curves of each subject studied in the supine (r = 0.94-1.00, all P < 0.01) and upright (r = 0.90-0.98, all P < 0.01) positions. A two-compartment model was the minimal model necessary to simultaneously describe the kinetics of NE in the supine and upright positions. The NE input rate into the extravascular compartment 2, estimated with the minimal model, increased with upright posture (1.87±0.08 vs. 3.25±0.2 pg/mm per Mi2, P < 0.001). Upright posture was associated with a fall in the volume of distribution of NE in compartment 1 (7.5±0.6 vs. 4.7+0.3 liters, P < 0.001), and as a result of that, there was a fall in the metabolic clearance rate ofNE from compartment 1 (1.80±0.11 vs. 1.21±0.08 liters/min per m=n, P < 0.001). We conclude that a two-compartment model is the minimal model that can accurately describe the kinetics of distribution and metabolism of NE in humans.