KINETICS OF HOMOVANILLIC-ACID AND DETERMINATION OF ITS PRODUCTION-RATE IN THE RHESUS-MONKEY

Homovanillic acid (HVA) [dopamine metabolite] labeled with 2 deuterium atoms (d2-HVA) was used to label the peripheral body pool of endogenous HVA (d0-HVA). D2-HVA was rapidly i.v. injected into rhesus monkeys (Macaca mulatta) and concentrations of both d2- and d0-HVA in sequential samples of blood serum and urine determined by gas chromatography-mass spectrometry. Parameters describing the distribution and elimination of HVA, and its pool size, turnover and synthesis rate were then calculated. The decline of serum d2-HVA concentration with time is multiexponential, with a biological half-life ranging from 35.9-102 min in the 4 monkeys studied. The apparent volume of distribution of d2-HVA in the body was 0.813-1.17 l/kg. Serum clearance was 7.28-18.2 ml/kg per min. For most animals, only about 50% of the administered dose of d2-HVA was recovered unchanged in the urine. Renal clearance ranged from 3.79-17.0 ml/kg per min, and d0-HVA excretion rates ranged from 19.5-64.1 .mu.g/h. The size of the peripheral body pool of HVA, calculated from serum kinetic parameters, was 63.3-80.7 .mu.g; HVA turnover was 5.43-13.9 .mu.g/l per h; and HVA production rate was calculated to be 36.6-84.3 .mu.g/h (5.23-12.6 .mu.g/kg per h).