Drug Investigation

, Volume 3, Issue 5, pp 317–323 | Cite as

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

  • F. K. Alavi
  • Cyril R. Clarke
  • S. Sangiah
  • K. D. Berlin
  • S. A. Zisman
  • C. L. Chen
  • G. Garrison
  • B. J. Scherlag
  • R. Lazzara
Original Research Article
First Online:

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.

Keywords

Quinidine Drug Invest Antiarrhythmic Agent Pharmacokinetic Disposition Adverse Central Nervous System Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Adis International Limited 1991

Authors and Affiliations

  • F. K. Alavi
    • 1
  • Cyril R. Clarke
    • 1
  • S. Sangiah
    • 1
  • K. D. Berlin
    • 2
  • S. A. Zisman
    • 2
  • C. L. Chen
    • 1
  • G. Garrison
    • 2
  • B. J. Scherlag
    • 3
  • R. Lazzara
    • 3
  1. 1.Department of Physiological Sciences, College of Veterinary MedicineOklahoma State UniversityStillwaterUSA
  2. 2.Department of Chemistry, College of Arts and SciencesOklahoma State UniversityStillwaterUSA
  3. 3.VA Medical CenterOklahoma CityUSA

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