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pubmed-article:7646568pubmed:abstractTextGLG-V-13 (3-[4-(1H-imidazol-1-yl)benzoyl]-7-isopropyl-3,7-diazabicyclo [3.3.1] nonane dihydroperchlorate, CAS 155029-33-7) has been shown to be a potent class III antiarrhythmic agent. The oral and intravenous pharmacokinetics and plasma protein binding of GLG-V-13 in dogs and in rabbits have now been investigated. Plasma GLG-V-13 concentration-time profiles, following an i.v. bolus dose of 6 mg/kg, were fitted to a 2-compartment model. The volume of distribution at steady state (Vd(ss)), the total systemic (ClB), and the elimination half-life (t1/2 beta) were 4.441 l/kg, 1.113 l/h/kg, and 2.485 h in dogs and 3.723 l/kg, 1.548 l/h/kg, and 1.401 h in rabbits. Following i.v. dosing, approximately 9.38% of the parent compound was excreted in dogs urine (0-72 h). Changes in plasma GLG-V-13 concentrations, after oral administration of GLG-V-13 (6 mg/kg), were best described by the 1-compartment pharmacokinetic model. The tmax and Cmax were 1.69 h, 0.54 mg/l in dogs and 1.44 h, 0.35 mg/l in rabbits. On oral administration, GLG-V-13 was moderately eliminated (t1/2kel' 1.867 h-1 in dogs and 3.961 h-1 in rabbits, respectively). Oral bioavailability was estimated to be 53.2% +/- 11.3% in dogs and 66.7% +/- 7.7% in rabbits. About 8.74% of the oral dose (6 mg/kg) was excreted via the dog urine (0-72 h). In vitro binding of GLG-V-13 to dog plasma protein was 29.4 +/- 9.90% (from 0.5 to 4 mg/l). Ex vivo binding of GLG-V-13 to dog plasma protein was 10.4 +/- 7.20%.(ABSTRACT TRUNCATED AT 250 WORDS)lld:pubmed
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pubmed-article:7646568pubmed:authorpubmed-author:ChenC LCLlld:pubmed
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pubmed-article:7646568pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:7646568pubmed:articleTitlePharmacokinetics and plasma protein binding of the new potent class III antiarrhythmic agent 3-[4-(1H-imidazol-1-yl)benzoyl]-7-isopropyl-3, 7-diazabicyclo[3.3.1]nonane dihydroperchlorate.lld:pubmed
pubmed-article:7646568pubmed:affiliationDepartment of Physiological Sciences, Oklahoma State University, Stillwater, USA.lld:pubmed
pubmed-article:7646568pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:7646568pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed