Kinetics of Homovanillic Acid and determination of its production rate in the rhesus monkey

Abstract

Homovanillic acid (HVA) labelled with two deuterium atoms (d 2-HVA) was used to label the peripheral body pool of endogenous HVA (d 0-HVA). D 2-HVA was rapidly injected intravenously into Rhesus monkeys and concentrations of both d 2- and d 0-HVA in sequential samples of blood serum and urine determined by gas chromatography-mass spectrometry. Parameters describing the distribution and elimination of HVA, as well as its pool size, turnover, and synthesis rate were then calculated. Results indicate that the decline of serum d 2-HVA concentration with time is multiexponential, with a biological half-life ranging from 35.9 to 102 min in the four monkeys studied. The apparent volume of distribution of d 2-HVA in the body was 0.813–1.17 1/kg. Serum clearance was 7.28–18.2 ml/kg/min. For most animals, only about 50% of the administered dose of d 2-HVA was recovered unchanged in the urine. Renal clearance ranged from 3.79 to 17.0 ml/kg/min, and d 0-HVA excretion rates ranged from 19.5 to 64.1 μg/hr. The size of the peripheral body pool of HVA, calculated from serum kinetic parameters, was 63.3–80.7 μg; HVA turnover was 5.43–13.9 μg/1/hr; and HVA production rate was calculated to be 36.6–84.3 (5.23–12.6 μg/kg/hr).