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Disposition of BRB-I-28 (7-benzyl-7-aza-3-thiabicyclo[3.3.1]nonane hydroperchlorate), a Novel Antiarrhythmic Agent

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Summary

The aim of this study was to characterise the pharmacokinetic disposition and tissue distribution of BRB-I-28 (7-benzyl-7-aza-3-thiabicyclo[3.3.1]nonane hydroperchlorate) in rats. The pharmacokinetic disposition was studied by collecting blood samples before and at frequent intervals after intracardiac or oral administration of 14C-labelled BRB-I-28. Two-compartment and 1-compartment pharmacokinetic models were used to describe blood concentration-time profiles after intracardiac and oral administration, respectively. After intracardiac administration, the half-life of elimination (t1/2β)from blood ranged from 4.66 to 9.91 hours and the apparent volume of distribution (Vd(area)) ranged from 3.131 to 6.239 L/kg. Oral dosing resulted in rapid and extensive absorption (bioavailability ± 80%). Distribution of radioactivity into heart, kidney, brain, liver, and perirenal fat was measured by sacrificing rats at various time intervals after oral administration of 14C-labelled BRB-I-28. Extensive distribution of radioactivity occurred in highly perfused organs, particularly liver, kidney and heart. However, levels of radioactivity in brain were low.

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Authors and Affiliations

  1. Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK, 74078, USA

    F. K. Alavi,  Cyril R. Clarke, S. Sangiah & C. L. Chen

  2. Department of Chemistry, College of Arts and Sciences, Oklahoma State University, Stillwater, Oklahoma, USA

    K. D. Berlin, S. A. Zisman & G. Garrison

  3. VA Medical Center, Oklahoma City, Oklahoma, USA

    B. J. Scherlag & R. Lazzara

Authors
  1. F. K. Alavi
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  2. Cyril R. Clarke
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  3. S. Sangiah
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  4. K. D. Berlin
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  5. S. A. Zisman
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  6. C. L. Chen
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  7. G. Garrison
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  8. B. J. Scherlag
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  9. R. Lazzara
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Alavi, F.K., Clarke, C.R., Sangiah, S. et al. Disposition of BRB-I-28 (7-benzyl-7-aza-3-thiabicyclo[3.3.1]nonane hydroperchlorate), a Novel Antiarrhythmic Agent. Drug Invest. 3, 317–323 (1991). https://doi.org/10.1007/BF03259745

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  • DOI: https://doi.org/10.1007/BF03259745

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