Human in vivo metabolism study of LGD-4033 / Argyro G. Fragkaki, Panagiotis Sakellariou, Polyxeni Kiousi, Nassia Kioukia-Fougia, Maria Tsivou, Michael Petrou, Yiannis Angelis. - (Drug Testing and Analysis 10 (2018) 11-12 (November-December); p. 1635-1645)
- PMID: 30255601
- DOI: 10.1002/dta.2512
Human in vivo metabolism study of LGD-4033 / Argyro G. Fragkaki, Panagiotis Sakellariou, Polyxeni Kiousi, Nassia Kioukia-Fougia, Maria Tsivou, Michael Petrou, Yiannis Angelis. - (Drug Testing and Analysis 12 (2020) 1 (January); p. 164)
- DOI: 10.1002/dta.2700. Epub 2019 Nov 17.
- PMID: 31984662
Selective androgen receptor modulators (SARMs) are an emerging class of therapeutics targeted to cachexia, sarcopenia, and hypogonadism treatment. LGD-4033 is a SARM which has been included on the Prohibited List annually released by the World Anti-Doping Agency (WADA). The aim of the present work was the investigation of the metabolism of LGD-4033 in a human excretion study after administration of an LGD-4033 supplement, the determination of the metabolites' excretion profiles with special interest in the determination of its long-term metabolites, and the comparison of the excretion time of the phase I and phase II metabolites. The results were also compared to those derived from previous LGD-4033 studies concerning both in vitro and in vivo experiments. Supplement containing LGD-4033 was administered to one human male volunteer and urine samples were collected up to almost 21 days. Analysis of the hydrolyzed (with β-glucuronidase) as well as of the non-hydrolyzed samples was performed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) in negative ionization mode and revealed that, in both cases, the two isomers of the dihydroxylated metabolite (M5) were preferred target metabolites. The gluco-conjugated parent LGD-4033 and its gluco-conjugated metabolites M1 and M2 can be also considered as useful target analytes in non-hydrolyzed samples. The study also presents two trihydroxylated metabolites (M6) identified for the first time in human urine; one of them was recently reported in an LGD-4033 metabolism study in horse urine and plasma.