The pharmacokinetics of tryptophan, the temporal occurence of kynurenine (KYN) and 3-hydroxykynurenine (3-HK) in plasma and urine, and the effect of nicotinamide on tryptophan metabolism were studied in 6 healthy subjects after oral administration of L-tryptophan 100 mg per kg body weight. The peak concentration of tryptophan in plasma occurred after 1 to 2 h, tryptophan disappeared linearly from 2 to 5 h and exponentially from 5 to 8 h. Urinary tryptophan excretion was negligible. The peak concentration of KYN in plasma occurred after 4 h and it was correlated significantly with the area under the plasma curve (AUC) of KYN of the subjects investigated. The AUC in plasma of KYN was significantly correlated with urinary KYN excretion within individuals, but not in the group as a whole. The data suggest that KYN was reabsorbed by renal tubules and that the degree of reabsorption was subject to large interindividual variation. The peak concentration in plasma of 3-HK occurred 11 min later than that of KYN. The results suggest that the net tubular effect on 3-HK was secretion. Pre-treatment with nicotinamide (0.5 g three times daily) resulted in considerable decreases in AUC in plasma, and in urinary excretion of KYN and 3-HK, indicating inhibition of liver tryptophan pyrrolase. The concomitant increase in AUC in plasma of free and total tryptophan was insignificant.
As only a relatively small amount of tryptophan is catabolized by tryptophan pyrrolase following an L-tryptophan load, cautious interpretation is recommended of urinary KYN excretion as an indicator of tryptophan break down in investigation of different subjects.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Altman K, Greengard O (1966) Correlation of kynurenine excretion with liver tryptophan pyrrolase levels in disease and after hydrocortisone induction. J Clin Invest 45: 1527–1534
Badawy AA-B, Evans M (1976) The regulation of rat liver tryptophan pyrolase activity by reduced nicotinamide-adenine dinucleotide (phosphate). Biochem J 156: 381–390
Bloxam DL, Warren WH, White PJ (1974) Involvement of the liver in the regulation of tryptophan availability. Possible role in the responses of liver and brain to starvation. Life Sci 15: 1443–1455
Brown RR (1980) Tryptophan metabolism in humans — perspectives and predictions. Paper read on 3rd meeting of the International Study Group for Tryptophan Research, Kyoto, Japan, August 4–7
Cho-Chung YS, Pitot HC (1967) Feedback control of rat liver tryptophan pyrrolase. J Biol Chem 242: 1192–1198
Cho-Chung YS, Pitot HC (1968) Regulatory effects of nicotinamide on tryptophan pyrrolase synthesis in rat liver in vivo. Eur J Biochem 3: 401–406
Chouinard G, Young SN, Annable L, Sourkes TL (1979) Tryptophan-nicotinamide, imipramine and their combination in depression. Acta Psychiat Scand 59: 395–414
D'Elia G, Hanson L, Raotma H (1978) L-tryptophan and 5-hydroxytryptophan in the treatment of depression — a review. Acta Psychiat Scand 57: 239–252
Domino EF, Krause RR (1974) Plasma tryptophan tolerance curves in drug free normal controls, schizophrenic patients and prisoner volunteers. J Psychiat Res 10: 247–261
Gailani S, Murphy G, Kenny G, Nussbaum A, Silvernail P (1973) Studies on tryptophan metabolism in patients with bladder cancer. Cancer Res 33: 1071–1077
Green AR, Bloomfield MR, Woods HF, Seed M (1978) Metabolism of an oral tryptophan load by women and evidence against the induction of tryptophan pyrrolase by oral contraceptives. Br J Clin Pharmacol 5: 233–241
Green AR, Woods HF, Joseph MH (1976) Tryptophan metabolism in the isolated perfused liver of the rat — effects of tryptophan concentration, hydrocortisone and allopurinol on tryptophan pyrrolase activity and kynurenine formation. Br J Pharmacol 57: 103–114
Greenwood MH, Lader MH, Kantameneni BD, Curzon G (1975) The acute effects of oral (-)-tryptophan in human subjects. Br J Clin Pharmacol 2: 165–172
Hartmann E (1977) L-tryptophan — a rational hypnotic with clinical potential. Am J Psychiat 134: 366–370
Joseph MH, Risby D (1975) The determination of kynurenine in plasma. Clin Chim Acta 63: 197–204
Knox WE (1965) The regulation of tryptophan pyrrolase activity by tryptophan. In: Weber G (ed) Advances in enzyme regulation IV. Pergamon Press, New York
Michael AF, Drummond KN, Doeden D, Anderson JA, Good RA (1964) Tryptophan metabolism in man. J Clin Invest 43: 1730–1746
Møller SE (1975) A method for the separation of plasma amino acids by ion-exchange chromatography combined with a semiautomatic computation of plasma amino acid concentrations. J Chromatogr 104: 63–72
Møller SE, Kirk L, Fremming KH (1976) Plasma amino acids as an index for subgroups in manic depressive psychosis — correlation to effect of tryptophan. Psychopharmacology 49: 205–213
Paasche I, Scherber A (1977) Zur Kinetik des Tryptophans beim Menschen. Zbl Pharm Pharmakother Laboratoriumsdiagn 116: 483–488
Wolf H (1974) Studies on tryptophan metabolism in man. Scand J Clin Lab Invest 33: Suppl 136
Yamaguchi K, Shimoyama M, Gholson RK (1967) Measurements of tryptophan pyrrolasein vivo — induction and feedback inhibition. Biochim Biophys Acta 146: 102–110
Young SN, St-Arnaud-McKenzie D, Sourkes TL (1978) Importance of tryptophan pyrrolase and aromatic amino acid decarboxylase in the catabolism of tryptophan. Biochem Pharmacol 27: 763–767
Preliminary results from the nicotinamide study were presented at the 3rd meeting of the International Study Group for Tryptophan Research, Kyoto, Japan, 4–7th August 1980
About this article
Cite this article
Møller, S.E. Pharmacokinetics of tryptophan, renal handling of kynurenine and the effect of nicotinamide on its appearance in plasma and urine following L-tryptophan loading of healthy subjects. Eur J Clin Pharmacol 21, 137–142 (1981). https://doi.org/10.1007/BF00637514
- renal clearance
- tryptophan pyrrolase