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GSK3335065 displayed an apparent volume of distribution between 20.6\u00a0L and 44.6\u00a0L, a clearance between 0.462\u2009L\/h and 0.805\u2009L\/hr and a terminal half\u2010life between 31.3 and 34.5\u00a0hr. In the single subject who received 1.3\u00a0mg GSK3335065, changes in tryptophan pathway metabolites were observed consistent with the changes seen in preclinical species suggesting that KMO enzyme activity was partially inhibited. However, a broad complex ventricular tachycardia was observed in this subject, which was judged to be a Serious Adverse Event (SAE) and resulted in early termination of the study. While development of GSK3335065 was subsequently discontinued, significant confounding factors hinder a clear interpretation that the tachycardia was directly related to administration of the compound.<\/jats:p>","DOI":"10.1111\/bcp.15010","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T07:11:20Z","timestamp":1627629080000},"page":"865-870","source":"Crossref","is-referenced-by-count":7,"title":["Assessment of the safety, pharmacokinetics and pharmacodynamics of GSK3335065, an inhibitor of kynurenine monooxygenase, in a randomised placebo\u2010controlled first\u2010in\u2010human study in healthy volunteers"],"prefix":"10.1111","volume":"88","author":[{"given":"Disala","family":"Fernando","sequence":"first","affiliation":[{"name":"Clinical Unit Cambridge Addenbrookes Centre for Clinical Investigation  Cambridge 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