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

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John D. G. McEvoy, Cynthia E. McVeigh and W. John McCaughey


Abstract

Injectable esters of 17β-19-nortestosterone (β-NT) have been used illegally for growth promotion in European Union (EU) cattle production. There are no data on oral bioavailability of free β-NT from β-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 β-NT at 0.1 mg kg1 body weight (NTiv), 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 β-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 β-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 β-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 µg l1). 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 β-NT which are significantly greater than those observed following injection of NT esters.


References

  1. EEC Directive 88/146, 1988, No. 70/16.
  2. E. H. J. M. Jansen, G. Zomer, R. H. van den Berg and R. W. Stephany, Vet. Q., 1984, 6, 101 Search PubMed.
  3. E. H. J. M. Jansen, H. van Blittersvijk and R. W. Stephany, Tijdschr. Diergeneesk., 1985, 110, 355 Search PubMed.
  4. P. Evrard, P. Gaspar and G. Maghuin-Rogister, J. Immunoassay, 1986, 7, 353 Search PubMed.
  5. M. Rapp and H. H. D. Meyer, Arch. Lebensmittelhyg., 1987, 38, 35 Search PubMed.
  6. L. A. Van Ginkel, R. W. Stephany, H. J. van Rossum, H. van Blitterswijk, P. W. Zoontjes, R. C. M. Hooijschuur and J. Zuydendorp, J. Chromatogr., 1989, 489, 95 CrossRef.
  7. L. J. Van Look, E. H. J. M. Jansen, R. H. van den Berg, G. Zomer, K. E. Vanoosthuyze and C. H. Van Peteghem, J. Chromatogr. B., Biomed. Appl., 1991, 564, 451 CrossRef CAS.
  8. E. Daeseleire, A. De Guesquière and C. Van Peteghem, J. Chromatogr., 1991, 562, 673 CrossRef CAS.
  9. K. Vanoosthuyze, E. Daeseleire, A. Van Overbeke, C. Van Peteghem and A. Ermens, Analyst, 1994, 119, 2655 RSC.
  10. L. Hendriks, B. Gielen, L. Leyssens and J. Raus, Vet. Rec., 1994, 134, 192 Search PubMed.
  11. Veterinary Applied Pharmacology and Therapeutics, ed. G. C. Brander, D. M. Pugh and R. J. Bywater, 4th edn., Baillière Tindall, London, 1982, p. 138 Search PubMed.
  12. G. Debruyckere, R. Desagher and C. Van Peteghem, Clin. Chem., 1992, 38, 1869 CAS.
  13. A. T. Kicman, D. A. Cowan, L. Myhre, S. Nilsson, S. Tomten and H. Oftebro, Clin. Chem., 1994, 40, 2084 CAS.
  14. H. G. Pope and D. L. Katz, Psychiatric Ann., 1992, 22, 24 Search PubMed.
  15. C. E. Yesalis, N. J. Kennedy, A. N. Kopstein and M. S. Bahrke, J. Am. Med. Assoc., 1993, 270, 1217 Search PubMed.
  16. A. Ruokonen and R. Vihko, J. Steroid Biochem., 1974, 5, 33 Search PubMed.
  17. J. D. G. McEvoy, C. E. McVeigh, J. W. Currie, D. G. Kennedy and W. J. McCaughey, Vet. Res. Commun., in the press Search PubMed.
  18. G. A. Baxter, C. T. Elliott, S. R. H. Crooks and W. J. McCaughey, Food Agric. Immunol., 1996, 8, 85.
  19. Clinical Pharmacokinetics: Concepts and Applications., ed. M. Rowland and T. N. Towzer, 2nd edn., Lea and Febiger, Philadelphia, London, 1989 Search PubMed.
  20. T. T. Kararli, Biopharm. Drug Dispos., 1995, 16, 351 CAS.
  21. T. R. Krishnan, I. Abraham and S. Craig, Biopharm. Drug Dispos., 1994, 15, 341 CAS.
  22. J. Van der Vies, Acta Endocrinol., 1965, 49, 271 Search PubMed.
  23. P. Geusens, Clin. Rheumatol., 1995, 14, Suppl. 3, 32.
  24. J. Van der Vies, Acta Endocrinol. Suppl., 1985, 271, 38 Search PubMed.
  25. K. Lusthof and K. Groen, personal communication.
  26. H. J. Horst, M. Höftge, M. Dennis, A. Coert, J. Geeleen and K. D. Voigt, Klin. Wochenschr., 1976, 54, 875 Search PubMed.
  27. J. D. G. McEvoy, C. E. McVeigh, W. J. McCaughey and D. G. Kennedy, Vet. Rec., in the press Search PubMed.
  28. H. P. Wijnand, A. M. G. Bosch and C. W. Donker, Acta. Endocrinol. Suppl., 1985, 271, 19 Search PubMed.
  29. R. Deyssig and M. Weissel, J. Clin. Endocrinol. Metab., 1993, 76, 1069 Search PubMed.
  30. C. J. Hannan, K. E. Friedl, A. Zold, T. M. Kettler and S. R. Plymate, Psychoneuroendocrinology, 1991, 16, 335 CrossRef CAS.
  31. W. Haasnoot, R. Schilt, A. R. M. Hamers and F. A. Huf, J. Chromatogr., 1989, 489, 157 CrossRef.
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