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

Summary

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.