Effect of 3,4-Dihydroxyphenylpyruvic Acid on the Metabolism of L-DOPA in Isolated Perfused Rat Liver

Abstract: The effect of 3,4-dihydroxyphenylpyruvic acid (DHPPA) on the hepatic metabolism of L-DOPA was investigated in isolated perfused rat liver. DHPPA decreased the initial hepatic extraction and prolonged the elimination half-life of L-DOPA when they were added simultaneously at the ratio 1:4 (L-DOPA: DHPPA) to the perfusate. At the ratio 1:1 DHPPA had no effect on the elimination half-life, but decreased the initial hepatic extraction of L-DOPA. When L-DOPA was added alone the initial loss of L-DOPA was 30% at 5 min. At that time the perfusion medium had passed the liver 2.5 times. Between 5 to 60 min. about 5% of the dose was extracted in a single pass through the liver. DHPPA added alone or together with L-DOPA was rapidly converted to L-DOPA, only about half of the DHPPA dose remained unmetabolized in the “plasma” at 2.5 min. The main metabolites in bile of all the compounds tested were conjugates of homovanillinic acid and 3,4-dihydroxyphenylacetic acid.