Abstract
Prohormones such as 19-norandrostenediol (estr-4-ene-3β,17β-diol) have been added to the list of prohibited substances of the World Anti-Doping Agency because they are metabolized to the common nandrolone metabolites norandrosterone and noretiocholanolone. So far, no studies on the metabolism and in vivo conversion of 19-norandrostenediol after oral or sublingual administration have been reported nor have had quantified data on resulting plasma nandrolone levels. In the present study, an open-label crossover trial with eight healthy male volunteers was conducted. After application of capsules or sublingual tablets of 19-norandrostenediol plasma concentrations of 19-norandrostenediol, nandrolone as well as major metabolites (19-norandrosterone and 19-noretiocholanolone) were determined using a validated assay based on gas chromatography/mass spectrometry. The administration of 100-mg capsules of 19-norandrostenediol yielded maximum plasma total concentrations (i.e., conjugated plus unconjugated compounds) of 1.1 ng/ml (±0.7) for 19-norandrostenediol, 4.0 ng/ml (±2.6) for nandrolone, 154.8 ng/ml (±130.8) for 19-norandrosterone, and 37.7 ng/ml (±6.9) for 19-noretiocholanolone. The use of 25-mg sublingual tablets resulted in 3.3 ng/ml (±1.0) for 19-norandrostenediol, 11.0 ng/ml (±6.4) for nandrolone, 106.3 ng/ml (±40.1) for 19-norandrosterone, and 28.5 ng/ml (±20.8) for 19-noretiocholanolone. Most interestingly, the pharmacologically active unconjugated nandrolone was determined after administration of sublingual tablets (up to 5.7 ng/ml) in contrast to capsule applications. These results demonstrate the importance of prohibiting prohormones such as 19-norandrostenediol, in particular, since plasma concentrations of nandrolone between 0.3 to 1.2 ng/ml have been reported to influence endocrinological parameters.
Footnotes
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This project has been carried out with support from WADA.
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.106.010165.
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ABBREVIATIONS: NL, 17β-hydroxy-estr-4-en-3-one (nandrolone); NA, 3α-hydroxy-5α-estran-17-one (19-norandrosterone); NE, 3α-hydroxy-5β-estran-17-one (19-noretiocholanolone); WADA, World Anti-Doping Agency; ND, estr-4-ene-3,17-dione (19-norandrostenedione); NDiol, estr-4-ene-3β,17β-diol (19-norandrostenediol); unc, unconjugated; p.a., pro analysi; d3-NE, 3,4,5-2H3-3α-hydroxy-5β-estran-17-one; d3-NDiol, 16,16,17-2H3-estr-4-ene-3β,17β-diol; d3-NL, 16,16,17-2H3-17β-hydroxy-estr-4-en-3-one; tot, total (conjugated plus unconjugated); LLE, liquid-liquid extraction; GC/MS, gas chromatography/mass spectrometry; ISTD, internal standard; LLOQ, lower limits of quantification; AUC, area under the plasma level-time curve; TMS, trimethylsilyl.
- Received March 14, 2006.
- Accepted May 17, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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