Absorption, Distribution and Excretion of L-DOPS in Animals

The absorption, distribution and excretion of (−)-(2 S, 3 R)-2-amino-3-hydroxy-3-(3, 4-dihydroxyphenyl) propionic acid (L-DOPS), an unphysiological amino acid and the precursor of norepinephrine, were investigated in mice, rats, dogs and Rhesus monkeys after oral or intravenous administration of 14C-L-DOPS labelled at C-3 position. 1. When 14C-L-DOPS (10 mg/kg) was administered orally to male animals, the maximal concentration (Cmax) in the serum was obtained within 1 hr after administration. Cmax levels were 9.5, 4.4, 3.6 and 2.7 μg eq/ml in dogs, Rhesus monkeys, mice and rats, respectively. The serum levels decreased rapidly with halflives of 1.3 to 4.2 hr. 2. After single oral administration of 10, 100 or 1000 mg/kg of 14C-L-DOPS to male rats, the maximal serum concentration of radioactivity for all doses appeared within 1 hr and then decreased rapidly. The area under the serum concentration-time curve for 14C was closely correlated with the administered dose. 3. There was no difference in 14C serum levels between male and female rats. 4. The radioactivity was distributed throughout organs and tissues after single oral administration of 14C-L-DOPS (10 mg/kg) to animals. Then the 14C levels rapidly decreased and 24 hr after administration only tracer concentrations were observed in the tissues. No particular accumulation in specific tissues was found. Relatively high concentrations of 14C were found in the kidney and liver of every species, and in the pancreas of mice and rats. 5. When 14C-L-DOPS (10 mg/kg) was administered orally to male animals, the excretion of a radioactivity to urine and feces was 60 ?? 72 % and 9 ?? 20 % of administered dose, respectively. Male rats excreted 14 % of the administered dose with expired air. The male rats excreted with bile 2.8 % of the dose during 48 hr.