Norepinephrine metabolism in humans: Kinetic analysis and model

Abstract

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. Steady-state NE specific activity in arterialized plasma during [3H]NE infusion and postinfusion plasma disappearance of [3H]NE were measured in eight healthy subjects in the supine and upright positions. Two exponentials were clearly identified in the plasma [3H]NE 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 μg/min per m2, 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 of NE from compartment 1 (1.80 ± 0.11 vs. 1.21 ± 0.08 liters/min per m2, 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.