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Pharmacokinetics of a nootropic agent, BMY-21502, and its metabolites in beagle dogs

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Summary

A preliminary investigation into the pharmacokinetics of BMY-21502, a nootropic agent, and two of its metabolites, BMY-42191 and BMY-40440, was performed in 4 beagle dogs. Following oral dosing of a solution of BMY-21502 (0.61 mmoles), plasma samples were obtained for 24h and analyzed for the three analytes by a validated HPLC assay. BMY-21502 was rapidly absorbed (Tmax=0.5 ±0.3 h), followed by a rapid decline of the plasma levels, (T1/2=0.95±0.1h) The hydroxy metabolite, BMY-42191, was rapidly formed and the peak concentrations in plasma were obtained by 2.88±0.2h. On the contrary, there was a considerable delay in the peaking of the ketone metabolite, BMY-40440 (Tmax=6h). The T1/2 values for BMY-40440 (5.58±0.5h) were longer than those for BMY-42191 (4.28±1.2 h). Comparison of AUC values for BMY-42191 (326.43±63.3 h.μM) with those of BMY-40440 (67.52 ±8.4 h.μM) or BMY-21502 (69.35±7.3 h.μM) indicated that BMY-42191 was the major circulating species in dog plasma. In conclusion, the preliminary data indicate that the metabolism of BMY-21502 is complex and may encompass hydroxy-ketone metabolic interconversions, as reported for other xenobiotics.

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References

  1. Mattson R.J., Yevich J.P., Moon, S.L. (1990): BMY-21502, Drugs Future, 15, 336–337.

    Google Scholar 

  2. Moon S.L., Mattson R.J., Yocca F.D. et al. (1988): BMY-21502: a potential cognition enhancer that improves memory and enhances glucose metabolism in the aged hippocampus, Soc. Neuro Sci., 14, Abs 87.12.

  3. Mattson R.J., Loukas E.P., Moon S.L. et al. (1988): Novel pyrrolidinone derivatives possessing memory and cognition enhancing activities. Identification of BMY-21502 as a potential psychogeriatric agent. Proc. Natl ACS Meeting, Los Angeles.

  4. Mattson R.J., Loukas E.P., Yevich J.P., Eison M.S. (1988): Synthesis and amnesia reversal activity of a series of novel pyrrolidinone derivatives: identification of BMY-21502 as a potential treatment for cognitive disorders. Soc. Neuro Sci., 14, Abs 87.11.

  5. Mattson R.J., Yevich J.P., Mayol R.F., Brady M. (1992): The synthesis and identification of the major metabolites of BMS-181168 (BMY-21502). Proc. Natl ACS Meeting, Washington, DC.

  6. Stocking L.M., Santone K.S., Cole C.A., Mayol R.F. (1992): Metabolic profile of14CBMS-181168 in rat plasma, brain, liver, kidney and urine following oral administration. ISSX Proc., V2, 175.

  7. Farmen R.H., Muniak J.F., Pittman K.A. (1987): Management of pharmacokinetic data using HP-3357/main frame IBM interfacing. Drug Inf. J., 21, 141–152.

    Google Scholar 

  8. Prescott P. (1975): An approximate test for outliers in linear regression. Technometrics, 17, 129–132.

    Article  Google Scholar 

  9. Gibaldi M., Perrier D. (1982): Pharmacokinetics, 2nd edn. New York: Marcel Dekker.

    Google Scholar 

  10. Riegelman S., Collier P. (1980): The application of statistical moment theory to the evaluation of the in vivo dissolution time and absorption time. J. Pharmacokinet Biopharm., 8, 509–534.

    Article  CAS  PubMed  Google Scholar 

  11. Cummings A.J., Martin B.K., Park G.S. (1967): Kinetic consideration relating to accrual and elimination of drug metabolites. Br. J. Pharmacol. Chemother., 29, 136–149.

    CAS  PubMed  Google Scholar 

  12. Pang K.S., Gillette J.R. (1978): Kinetics of metabolite formation and elimination in the perfused rat liver preparation: differences between the elimination of preformed acetaminophen formed from phenacetin. J. Pharmacol. Exp. Ther., 207, 178–194.

    CAS  PubMed  Google Scholar 

  13. Pang K.S. (1985): A review of metabolite kinetics. J. Pharmacokinet. Biopharm., 13, 633–662.

    Article  CAS  PubMed  Google Scholar 

  14. Houston J.B. (1982): Drug metabolite kinetics. Pharmacol. Ther., 15, 521–552.

    Article  Google Scholar 

  15. Midha K.K., Hawes E.M., Hubbard J.W., Korchinski E.D., McKay G. (1987): Interconversion between haloperidol and reduced haloperidol in humans. J. Clin. Psychopharmacol., 7, 362–363.

    Article  CAS  PubMed  Google Scholar 

  16. Van Peer A., Woestenborghs R., Embrechts L., Heykants J. (1986): Pharmacokinetic approach to equilibrium between ketanserin and ketanserin-ol. Eur. J. Clin. Pharmacol., 31, 339–342.

    Article  PubMed  Google Scholar 

  17. Leinweber F-J., Greenhough R.C., Schwender C.F., Kaplan H.R., Di Carlo F.J. (1972): Bunolol metabolism by cell-free preparations of human liver: biosynthesis of dihyrobunolol. Xenobiotica, 2, 191–202.

    Article  CAS  PubMed  Google Scholar 

  18. Bjorkhem I., Hamberg M. (1971): Oxidation of fatty acids: enzymatic oxido-reduction of 17-hydroxystearic acid. J. Biol. Chem., 246, 7417–7420.

    CAS  PubMed  Google Scholar 

  19. Felsted R.L., Gee M., Bachur N.R. (1974): Rat liver daunorubin reductase: an aldo-keto reductase. J. Biol. Chem., 249, 3672–3679.

    CAS  PubMed  Google Scholar 

  20. Lane E.A., Levy R.H. (1985): Fractions metabolized in a triangular metabolic system: Cinoromide and two metabolites in the rhesus monkey. J. Pharmacokinet. Biopharm., 13, 373–386.

    Article  CAS  PubMed  Google Scholar 

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  1. Metabolism and Pharmacokinetics, Pharmaceutical Research Institute, Bristol-Myers Squibb Company, PO Box 4000, 08543-4000, Princeton, NJ, USA

    N. Srinivas & S. Kaul

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  1. N. Srinivas
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  2. S. Kaul
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Srinivas, N., Kaul, S. Pharmacokinetics of a nootropic agent, BMY-21502, and its metabolites in beagle dogs. European Journal of Drug Metabolism and Pharmacokinetics 23, 61–65 (1998). https://doi.org/10.1007/BF03189828

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