[Tryptophan metabolism in liver diseases: a pharmacokinetic and enzymatic study]

Abstract

Tryptophan is considered to be one of the agents involved in the pathogenesis of hepatic encephalopathy. In our study, we evaluated tryptophan metabolism in liver disease. A bolus of 1.5 g of L-tryptophan was administered intravenously to 14 patients with noncirrhotic liver disease, 40 patients with liver cirrhosis, and 8 healthy volunteers. As pharmacokinetic parameters, the half life, clearance, and volume of distribution of free and total tryptophan were determined using a biexponential formula. In addition, the activity of liver tryptophan pyrrolase, the key enzyme of tryptophan metabolism, was measured in liver biopsy specimens of 15 patients with noncirrhotic liver disease, 8 patients with cirrhosis of the liver, and 4 patients with histologically normal livers. Healthy subjects and patients with noncirrhotic liver disease both showed similar results in measured and calculated data. In contrast, patients with cirrhosis revealed significant alterations of the pharmacokinetic parameters of free and total tryptophan: the half-life was increased by 195% and 176%, the clearance was decreased by 73% and 34%, respectively, and the activity of tryptophan pyrrolase was decreased by 22%. The tryptophan transfer in cirrhosis amounted to only 0.75 +/- 0.03 g per 24 h compared with 2.6 +/- 0.34 g per 24 h in healthy individuals. The findings demonstrate that patients with cirrhosis show a marked reduction in their ability to metabolize tryptophan. This should be taken into account in the oral and parenteral nutrition of those patients.