Bioavailability of nortestosterone laurate from meat
Biobeschikbaarheid van nortestosteronlauraat uit vlees
Lusthof KJ , Groen K , Olling M , Ginkel L van
RIVM Report 328471003
A previous survey on the presence of anabolic steroid residues in minced meat intended for human consumption showed that in several samples residues of nortestosterone were present. Nortestosterone (NT, nandrolone) is an anabolic steroid drug illegally used in stock-breeding. In order to study the internal exposure to NT after ingestion, the bioavailability of NT after oral administration of nortestosterone laurate (NTL) was studied in the dog. The bioavailability was studied in six male beagle dogs in a one-period study design. Each dog received simultaneously, directly after the morning feeding: A) an intravenous dose of 0.15 mg/kg b.w. of radio-active labeled nortestosterone dissolved in glycofurol and B) an oral dose of 9 mg/kg b.w. unlabeled nortestosterone laurate as a suspension in water. Blood samples were regularly taken up to 24 hours after administration. Plasma was analysed for NT and NTL by using GC/MS after plasma extraction, HPLC purification and derivatisation, using deuterated NT as an internal standard. After intravenous administration the plasma levels of NT decreased monoexponentially with a half-life of approximately 15 minutes. After oral administration of NTL, maximum plasma levels of NTL and NT were obtained approximately two hours after dosing. The plasma levels of NTL were much higher than those of NT, and the terminal half-lives of NTL and NT were similar (0.9 plusminus 0.5 and 1.3 plusminus 0.1 h, respectively). The exposure to NT after oral administration of NTL was about 2% of the exposure after an equivalent intravenous dose of NT. The results suggest that the conversion of NTL to NT is a much slower process than the elimination of NT. The low exposure to NT after an oral dose of NTL may be caused by the slow formation of NT as well as poor absorption of NTL. From this study it can be concluded that the default assumption that the bioavailability of nortestosterone laurate from meat equals 100%, overestimates the consumer risk by a factor of 10.