Inhibitory Effects of Diclofenac on Steroid Glucuronidation In Vivo Do Not Affect Hair-Based Doping Tests for Stanozolol.

Gergely Zachár,Declan Naughton,Naved Deshmukh,Andrea Petróczi,Iltaf Shah,Andrea Székely,James Barker

doi:10.3390/molecules22060976

Abstract

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3′-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1–3) and diclofenac (weeks 1–6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3′-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3′-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair, which holds considerable advantages over urinalysis for anti-doping tests.

Highlights

The major elimination and deactivation pathway for anabolic steroids (AS) and their phase I metabolites is through glucuronide conjugation followed by excretion in urine [1,2,3,4]
The experimental design featured the capability of assessing the effects of diclofenac on stanozolol profiles during co-administration and for a four week period after cessation of stanozolol to capture the effect on extended metabolism
In support of hair-based testing, this study provides strong evidence that detecting a synthetic steroid in hair is unaffected by temporary compromised metabolism via concomitant administration of non-steroidal anti-inflammatory drugs (NSAIDs)

Summary

Introduction

The major elimination and deactivation pathway for anabolic steroids (AS) and their phase I metabolites is through glucuronide conjugation (phase II metabolism) followed by excretion in urine [1,2,3,4]. UGTs are involved in the metabolism of AS, but they contribute to the metabolism of various compounds including non-steroidal anti-inflammatory drugs (NSAIDs) [1]. The NSAIDs ibuprofen and diclofenac are commonly used by athletes for the treatment of pain and inflammation [7,8,9,10,11,12], and it has been reported that both drugs competitively inhibit the testosterone glucuronidation activity of UGT2B17 and other. A recent study investigated the effects of two NSAIDs (ibuprofen and diclofenac) on excretion of a single dose of testosterone in 23 male volunteers with two (39%), one (33%) or no (28%) allele of the UGT2B17 gene.

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Discussion

Conclusion