Peroxisome Proliferator-Activated Receptor Delta Agonist (PPAR- δ) and Selective Androgen Receptor Modulator (SARM) Abuse: Clinical, Analytical and Biological Data in a Case Involving a Poisonous Combination of GW1516 (Cardarine) and MK2866 (Ostarine)

Abstract

A 43-year-old male, sport coach, presented him-self at the Emergency unit of a local hospital for epigastric pain, myalgia pain and severe headache. He claimed having used for some days a combination of GW1516 (cardarine), a peroxisome proliferator-activated receptor delta agonist (PPAR- δ) and MK2866 (ostarine), a selective androgen receptor modulator (SARM) to gain skeletal muscles. Cytolysis with marked increase of alanine aminotransferase or ALT (up to 922 UI/L) and aspartate aminotransferase or AST (up to 2558 UI/L) and massive rhabdomyolysis with elevated creatine phosphokinase or CPK (up to 86435 UI/L) were the main unusual biochemistry parameters. Using a specific liquid chromatography coupled to tandem mass spectrometry method, cardarine and ostarine tested positive in blood at 403 and 1 ng/mL, respectively. In urine, due to extensive metabolism, the parent GW1516 was not identified, while ostarine was at 88 ng/mL. Finally, both drugs were identified in hair (2 cm in length, brown in colour), at 146 and 1105 pg/mg for cardarine and ostarine, respectively. This clearly demonstrates repetitive abuse over the last 2 months. Asthenia was persistent for 2 weeks and 6 weeks after the admission, the subject fully recovered.

Systematic Review of Safety of Selective Androgen Receptor Modulators in Healthy Adults: Implications for Recreational Users

“…The large majority (88%, N = 15) reported DILI associated with SARM use. Other significant adverse events included one case of severe rhabdomyolysis (Kintz et al) and one case of bilateral asynchronous Achilles tendon ruptures (Gould et al) [ 14 , 15 ]. The case of rhabdomyolysis occurred in a 43-year-old male after cycling approximately 75 miles.…”

“…Aside from DILI and elevated ALT, there were concerning safety signals for musculoskeletal side effects. Both Clark et al (GSK2881078) and Kintz et al (case report) reported rhabdomyolysis [ 15 , 39 ]. In both the case report and Clark et al, the subjects were reported to have performed significant physical activity, and the association with the drug is not certain [ 39 ].…”

“…In the years 2020–2022, there has been a rapid increase in the number of published case reports of drug-induced liver injury (DILI) associated with SARM abuse [ 11 , 12 , 13 ]. There have also been case reports of rhabdomyolysis and tendon rupture associated with SARM abuse [ 14 , 15 ]. The mechanisms for these injuries remain unknown.…”

Annual banned‐substance review—Analytical approaches in human sports drug testing 2021/2022–

“…Also, one bishydroxylated metabolite of S‐23 was detected in vivo, whereas hair samples collected after the single‐dose exposure to S‐23 did not result in any finding at a method LOD of 0.1 pg/ml. This demonstrates also well the necessity of caution when interpreting paired test results obtained from different matrices 109 if not originating from intoxication cases 110 …”

“…This demonstrates also well the necessity of caution when interpreting paired test results obtained from different matrices 109 if not originating from intoxication cases. 110 Similarly, the interpretation of urinary SARM findings has been the subject of considerable debate in the past, with low concentrations of prohibited substances or their metabolites potentially originating from either recent contamination or past doping practices. In order to provide additional data into elimination profiles of frequently observed SARMs, LGD-4033 and RAD140 (Figure 1, 2 and 4) were each administered to five male volunteers in single and multiple microdoses of 1, 10, and 50 μg, and urine was collected up to 47 days after administration.…”