Residues of nortestosterone esters at injection sites. Part 1. Oral bioavailability

Injectable esters of 17 beta-19-nortestosterone (beta-NT) have been used illegally for growth promotion in European Union (EU) cattle production. There are no data on oral bioavailability of free beta-NT from beta-NT esters. Adult non-pregnant female Landrace pigs (n = 4) were fitted with jugular vein cannulae and were treated as follows with an appropriate 'flushing out' period between each treatment: an intravenous bolus of beta-NT at 0.1 mg kg-1 body weight (NTi.v.), 300 mg nortestosterone phenylpropionate (NTPP) in oil of arachis administered per os (NTPPoil) and 300 mg NTPP in aqueous suspension administered per os (NTPPaq). Blood samples were taken for up to 24 h and analysed for free beta-NT by enzyme immunoassay. Calculation of the area under the plasma time concentration curve (AUC), allowed absolute bioavailability estimations for both oral treatments. Mean bioavailability of beta-NT following NTPPaq was 0.35% (range 0.25-0.41%) compared to 2.25% (range 0.86-2.85%) for NTPPoil. Mean +/- standard error of mean time of maximum plasma concentration (Tmas) of free beta-NT occurred earlier (2.3 +/- 0.6 h) with NTPPoil compared to NTPPaq (10.3 +/- 1.03 h) and the maximum plasma concentration (Cmax) was also greater for NTPPoil compared to NTPPaq (36.1 +/- 6.49 vs. 3.2 +/- 0.31 micrograms l-1). It is concluded that the presence of arachis oil enhances the absorption of NTPP. Notwithstanding the possible effects that cooking and other food processing may have on such injection site residues, extrapolation of these results to man suggests that consumption of NTPP-containing injection sites may result in peak plasma concentrations of free beta-NT which are significantly greater than those observed following injection of NT esters.