The Probenecid‐story – A success in the fight against doping through out‐of‐competition testing

Abstract

The effectiveness of doping control in sport has been improved continuously during the past 50 years. One of the major steps forward was the introduction of unannounced and targeted out-of-competition testing in order to control the misuse of anabolic-androgenic steroids (AAS), mainly during the end of the 1980s. It also led to the misuse of masking agents in case a surprise control was performed. Athletes tried to be "prepared", when the doping control officer showed up. The disclosure of the masking agent probenecid in 1987 is a perfect example of a memorable finding, of a suspected and purported case of performance manipulation. Probenecid and its metabolites were identified in five urine samples collected from Norwegian athletes in an out-of-competition test, while they were staying and training in the USA. Probenecid is a drug that reduces the urinary excretion of AAS from the body. It was the first time that it had showed up in a doping control sample. The athletes were sanctioned for hampering the analysis of their urine sample, although probenecid was not yet specified on the Prohibited List. Its detection was the result of a successful collaboration of laboratories and investigative diligence and enthusiasm following up suspicious observations in the actual samples. Immediately afterwards probenecid was added to the Prohibited List for 1988 as well as including the manipulation of doping control samples. K E Y W O R D Sdoping, probenecid, sample manipulation, target testing

Blockade of Organic Anion Transport in Humans After Treatment With the Drug Probenecid Leads to Major Metabolic Alterations in Plasma and Urine

“…These metabolites, which include purine derivatives, aromatic amino acid derivatives, and others are primarily excreted through the urine. Steroids were also decreased in the urine, which is consistent with the use of probenecid to mask levels of androgenic steroids in urine samples 52 . Like the plasma, it appears that the urine metabolome is more influenced by the inhibition of the OATs than URAT1.…”

“…Steroids were also decreased in the urine, which is consistent with the use of probenecid to mask levels of androgenic steroids in urine samples. 52 Like the plasma, it appears that the urine metabolome is more influenced by the inhibition of the OATs than URAT1. In the context of OAT1/3 (basolateral uptake transporters) vs. URAT1 (apical uptake transporter), metabolites elevated in the plasma and decreased in the urine are linked to OAT1/3, whereas metabolites decreased in the plasma and elevated in the urine are linked to URAT1.…”

Probenecid affects muscle Ca2+ homeostasis and contraction independently from pannexin channel block

“…Probenecid also gained popularity within the sport performance doping field, presumably because of its capacity to reduce the excretion of anabolic-androgenic steroids ( Hemmersbach, 2020 ). Nonetheless, to mention that the exact conditions of dosing for that particular purpose remain poorly documented.…”

Annual banned‐substance review: Analytical approaches in human sports drug testing 2019/2020

“…Masking the misuse of banned substances by means of drugs or sample manipulation received increasing attention with the systematic installation of unannounced out‐of‐competition controls in the late 1980s, as revisited by Hemmersbach in the context of probenecid within a series on memorable findings in sports drug testing 152 . While the masking properties of diuretics are today significantly more limited than 30 years ago, diuretics are still considered as potentially performance‐enhancing in selected sports 153 .…”