Determination of homovanillic acid turnover in man
Abstract
Homovanillic acid (HVA) labelled with five deuterium (d) atoms was used to determine the total body turnover of HVA, the size of the peripheral body pool of HVA and HVA elimination characteristics in five healthy men. After i.v. injection of 5.5 μmoles (1 mg) of HVA-d5 the levels of HVA-d5 and endogenous HVA (HVA-do) in plasma and urine were followed by mass fragmentography using HVA-d2 as the carrier and internal standard. Following an initial distribution phase of 10–20 minutes the plasma elimination curve of HVA-d5 was monoexponential with a mean of 0.66 hrs. The apparent volume of distribution (VD) approximated the volume of the body water. The content of HVA in the peripheral body pool calculated from the plasma levels of HVA-do and VD was 3.4 moles. The urinary HVA excretion rate (mean 1.70 moles/hour) was 45% of the total body turnover, the recovery of urinary HVA-d5 was 48% of the mean body clearance. Together the results indicate that about 50% of the HVA formed in the body is eliminated by mechanisms other than renal excretion.
References (7)
- B. Sjöquist et al.
Life Sci.
(1973) - D.F. Sharman
Brit. Medical Bulletin
(1973) - B. Sjöquist et al.
Anal. Chem.
(1972)
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Time course of the corticosteroid-dopaminergic interaction during metyrapone and dexamethasone administration
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Influence of renal clearance on peripheral homovanillic acid measurements in healthy subjects and schizophrenic patients
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Acute effects of neuroleptics on unmedicated schizophrenic patients and controls
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1988, Biological PsychiatryIsolation of 2-hydroxycarboxylic acids with a boronate affinity gel
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