The disposition of intravenous L-tryptophan in healthy subjects and in patients with liver disease.
The disposition of free and of total tryptophan following an intravenous load of 1.5 g of L-tryptophan was evaluated in eight patients with non-cirrhotic liver disease, 40 patients with cirrhosis of the liver (21 Child's A, 15 Child's B, 4 Child's C) and in 14 healthy subjects. Cirrhosis affected disposition of tryptophan by (a) decreasing the clearance of both free and total tryptophan by 64% (P less than 0.001) and 34% (P less than 0.01), respectively, (b) by increasing the apparent volume of distribution of total tryptophan by 42% (P less than 0.01) by expansion of the peripheral compartment, resulting in (c) a threefold increase in the half-life of tryptophan. Apart from a reduction in free tryptophan clearance, these changes in tryptophan disposition were not apparent in patients with non-cirrhotic liver disease. Elevated fasting free tryptophan plasma concentrations are an indicator of impaired tryptophan metabolism in cirrhosis. They result from a decreased hepatic clearance of tryptophan rather than from a reduction in tryptophan protein binding. This study emphasises the markedly differing pharmacokinetic behaviour of tryptophan in cirrhotic patients compared with normal subjects and with patients with non-cirrhotic liver disease.
D000328:Adult; D000368:Aged; D006801:Humans; D007262:Infusions, Intravenous; D007700:Kinetics; D008103:Liver Cirrhosis / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D011485:Protein Binding; D014364:Tryptophan / Q000378:metabolism*
D014364:Tryptophan