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1000
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Abstract/Summary
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Abstract: Increased activity of the tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase
(IDO) is associated with immunological and neurological disorders, and inhibition of its enzyme activity
could be a therapeutic approach for treatment of these disorders. The aim of the present study was
to establish a large animal model to study the accumulation of the potential IDO inhibitor
1-methyltryptophan (1-MT) in blood and different organs of domestic pigs (Sus scrofa domestica).
Because 1-MT has not been previously evaluated in pigs, the pharmacokinetics of a single
subcutaneous 1-MT application was investigated. Based on this kinetic study, a profile for repeated
1-MT applications over a period of five days was simulated and tested. The results show that a single
administration of 1-MT increases its concentrations in blood, with the maximum concentration being
obtained at 12 h. Repeated daily injections of 1‑MT generated increasing plasma concentrations
followed by a steady-state after two days. Twelve hours after the final application, accumulation of
1-MT was observed in the brain and other organs, with a substantial variability among various tissues.
The concentrations of 1-MT measured in plasma and tissues were similar to, or even higher, than
those of tryptophan. Our data indicate that repeated subcutaneous injections of 1-MT provide a
suitable model for accumulation of 1-MT in plasma and tissues of domestic pigs. These findings
provide a basis for further research on the immunoregulatory functions of IDO in a large animal model.
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