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Here we demonstrate measurement of peripheral 5\u2010HT synthesis in healthy subjects by monitoring the produced [<jats:sup>13<\/jats:sup>C<jats:sub>10<\/jats:sub>]\u20105\u2010HT (h\u20105\u2010HT) in EDTA\u2010whole blood from three doses of orally administered [<jats:sup>13<\/jats:sup>C<jats:sub>11<\/jats:sub>]\u2010Trp (h\u2010Trp) tracer. h\u2010Trp was rapidly absorbed and distributed in a multiphasic manner, followed by a slower terminal elimination phase. The h\u20105\u2010HT synthesis rate was dependent on h\u2010Trp dose, appeared linear up to 12 hours postdose, and could be reliably assessed for the two highest doses. The human data was compared to similar studies in rats and dogs, finding larger interspecies differences in the h\u20105\u2010HT synthesis rate than in 5\u2010HT levels. In future studies, the h\u20105\u2010HT synthesis rate can be used to assess disease\u2010dysregulated 5\u2010HT synthesis or quantify the pharmacodynamics of 5\u2010HT synthesis inhibitors.<\/jats:p>","DOI":"10.1002\/cpt.1087","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T04:26:37Z","timestamp":1523939197000},"page":"1260-1267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Assessment of Peripheral Serotonin Synthesis Using Stable Isotope\u2010Labeled Tryptophan"],"prefix":"10.1111","volume":"104","author":[{"given":"Martine","family":"Gehin","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Idorsia Pharmaceuticals Ltd Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W.D.","family":"Welford","sequence":"additional","affiliation":[{"name":"Drug Discovery Idorsia Pharmaceuticals Ltd Allschwil 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