Norepinephrine Metabolism in Humans Studied by Deuterium Labelling: Turnover of 4-Hydroxy-3-methoxyphenylglycol

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Abstract
D,L(.+-.)-4-Hydroxy-3-methoxyphenylglycol (HMPG [norepinephrine metabolite]) labeled with 3 deuterium atoms was used to study turnover of plasma free HMPG following an i.v. injection. Ten healthy men were given a pulse dose of either 4.3 or 2.2 .mu.mol of labeled HMPG ([2H3]HMPG piperazine salt). Plasma and urine levels of both endogenous and labeled HMPG were subsequently followed by gas chromatography-mass spectrometry with selected ion detection. Kinetic calculations based upon a single-compartment model were consistent with a monoexponential elimination of plasma-free HMPG. The half-life of HMPG was 0.46 and 0.78 h (mean values in the 2 dose groups). The HMPG production rate was 2.01 and 2.35 .mu.mol/h, and the urinary excretion rate of HMPG (free and conjugated) was 0.48 and 0.47 .mu.mol/h. The endogenous plasma level of free HMPG was 25 and 33 nmol/l. HMPG turns over rapidly and is further metabolized extensively. About 1/4 of the HMPG produced is excreted in urine as free and conjugated HMPG.