A study to determine the influence of probenecid (benemid) on the urinary excretion of androsterone

Thesis

The aim of this study was to determine the influence of probenecid on the urinary excretion of anabolic-androgenic steroids. Androsterone is an endogenous steroid and since it is excreted in high concentrations in urine, it was used as a representative of anabolic steroids. It was also used because it would be unethical to give anabolic-androgenic steroids to healthy volunteers just to study the influence of probenecid on the excretion of anabolic steroids. A literature survey of the relevant publications reveals a lack of information regarding the influence of probenecid on the urinary excretion of anabolic steroids as well as endogenous steroids. A pilot study performed at the F ARMOVS Research Centre, Department of Pharmacology, Bloemfontein suggested a significant decrease on the urinary excretion of androsterone after the intake of probenecid. Twenty (20) healthy, male volunteers participated in an open, single-dose, randomised, two way, cross-over study with a drug-free interval of 7 days between treatment phases. Each subject received each of the following 2 treatments once in a randomised order: Treatment A: Placebo (control phase) + 200ml water. Treatment B: 4 x 500mg Probenecid tablets (Benemid®) + 200ml water. On the profile days (Day I and 8), the trial medication was taken at 08:00 with 200ml tap water. All subjects were required to take 200ml water hourly for the first four hours after drug administration. After administration urine collections were made at predetermined intervals over a peroid of 48 hours for the determination of androsterone and probenecid concentrations. Androsterone was quantified using a gas chromatograph-mass spectrometric method. The results showed that the lowest excretion of androsterone was found between 2 - 3 hours after administration of probenecid. A statistically significant decrease in the excretion rate of androsterone was seen from 2 to 8 hours after administration of a single dose of probenecid (4 x 500mg). The mean androsterone excretion rate for all fractional collection intervals in this period (1 - 2 h, 2 - 3 h, 3 - 4 h, 4 - 6 h, 6 - 8 h) were between 56% and 70% lower following administration of Benemid® compared to placebo. High doses of probenecid inhibit the urinary excretion of androsterone and therefore it will also inhibit the excretion of other anabolic steroids excreted as glucuronides in urine. Since the concentration of exogenous anabolic steroids in urine is usually very low, probenecid can decrease their concentration to below the limit of detection. Thus, probenecid can be used as a masking agent for the excretion of anabolic steroid glucuronides. This inhibition of the renal excretion of anabolic steroids by probenecid represents a manipulation of the urine sample in doping control and therefore probenecid was banned by the Medical Commission of the International Olympic Committee.