Yizi Decoction

Kampo prescriptions can cause drug‐induced lung injury (DLI) and acute respiratory distress syndrome (ARDS). However, severe respiratory failure induced by Otsujito (OJT) is extremely rare. High‐dose steroid pulse therapy is generally given to patients with severe DLI.

A 63‐year‐old man with respiratory distress was admitted to our hospital. The patient was diagnosed with severe ARDS caused by OJT, which had been prescribed 4 weeks prior to admission. Thus, OJT was discontinued, and intensive care for ARDS, including ventilation and prone positioning, was implemented. His respiratory condition rapidly improved after treatment with an initial methylprednisolone dose (1.5 mg/kg/day). He was extubated on day 4 and discharged on day 16. The steroid dose was gradually reduced and discontinued by day 116.

A severe case of ARDS caused by OJT was successfully treated with low‐dose steroids and specialized intensive care.

The selective androgen receptor modulators are a recent class of anabolic agents, used to improve athletic performance. Among these molecules, there is (2 S)-N-(4-cyano-3-trifluoromethylphenyl)- 3-(3-fluoro-4-chlorophenoxyl)2-hydroxy-2-methyl-propanamide, commonly known as S-23. This molecule appeared very recently on the doping market. As a result, very few data are available in the literature, and nothing has been published about long-term effects of S-23. The authors focused on the detection of S-23 and its metabolites in human urine, following a single oral administration of approx. 8 mg to a volunteer, using standard ultra-performance liquid chromatography-triple quadrupole-mass spectrometry (UPLC-MS/MS), and ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UPLC-Q-TOF-MS). To the best of the authors knowledge, this seems to be the first study ever achieved on S-23. In vitro experiment was performed, using human liver microsomes, in order to investigate the potential CYP- and UGT-dependent S-23 metabolites. Four metabolites were produced, which were identified as hydroxy-S-23 (C₁₈H₁₂O₄N₂ClF₄: m/z [M-H^-] 431.0423); O-dephenylate-S-23 (C₁₂H₁₀O₃N₂F₃: m/z [M-H^-] 287.0647); S-23-glucuronide (C₂₄H₂₀O₉N₂ClF₄: m/z [M-H^-] 591.0794) and hydroxy-S-23-glucuronide (C₂₄H₂₀O₁₀N₂ClF₄: m/z [M-H^-] 607.0743). After consumption of S-23, the parent drug was detectable in hydrolyzed urine from 2 h post administration up to 28 days, with concentrations ranging between 0.5 and 93 ng/mL. In the urine, only one of the four metabolites identified in vitro was detected, hydroxy-S-23. This metabolite was detected up to 28 days. It does not seem to increase the window of detection of S-23 as the ratio between hydroxy-S-23 and the parent drug was always lower than 1. Another metabolite, dihydroxy-S-23, not identified in vitro, was identified in the urine of the volunteer. Hair sample, collected one month after the consumption of a single tablet, was negative for S-23 and hydroxy-S-23, with a LOQ at 0.1 pg/mg.