Title: Identification of the metabolites of ivermectin in humans
Running title: Identification of ivermectin metabolites
Phornpimon Tipthara1, Kevin C Kobylinski2, Markus Godejohann3, Borimas Hanboonkunupakarn1,4, Alison Roth5,6, John H Adams5, Nicholas J. White1,7, Podjanee Jittmala1,8, Nicholas P.J. Day1,7, Joel Tarning1,7
1Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
2Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
3AIC, Bruker BioSpin GmbH, Rheinstetten, Germany.
4Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
5Center for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida, USA.
6Department of Drug Discovery, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
7Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
8Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Acknowledgements: We thank Markus Winterberg and Siribha Apinan for their contribution to the MS experiments. We are grateful to the volunteers for their participation in the trial, the nurses of the Clinical Therapeutics Unit and the Mahidol University Hospital for Tropical Diseases for their support conducting the trial. This study was funded through a grant from the Bill & Melinda Gates Foundation (OPP1180249). The Mahidol Oxford Tropical Medicine Research Unit is funded by the Wellcome Trust of Great Britain.
Disclaimer: Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70–25.
Conflict of interest statement: The authors declare no conflicts of interest. We did not purchase any of the compounds or instruments mentioned in this article from Bruker.
Correspondence: Professor Joel Tarning, Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, THAILAND. Email: Joel@tropmedres.ac
Authorship contributions: P.T., K.C.K. and J.T. designed the research. P.T. performed MS experiments. P.T. analysed data and wrote the first draft of the manuscript. M.G. performed NMR experiments. P.J. and B.H. performed the clinical trial. A.R. and J.H.A. performed the hepatocytes experiments. All authors contributed to the organization of the study and the final draft of the manuscript.