A pharmacokinetic study on Z-(+/-)-2-(1-benzylindole-3-yl-methylene)azabicyclo[2.2.2]octane-3-ol; a novel radio-sensitization agent.
OBJECTIVE
The purpose of this research was to characterize the pharmacokinetic parameters and to evaluate the absolute bioavailability of the targeted compound: Z-(+/-)-2-(1-benzylindole-3-yl-methylene)azabicyclo[2.2.2]octane-3-ol (BMABO), a novel radio-sensitization agent, after oral delivery.


METHODS
Sprague-Dawley rats received a single oral dose of 20 mg/kg and this was compared with intravenous administration of the compound (1 mg/kg). Blood samples were collected at different time points, and plasma BMABO concentrations were determined using a new sensitive and specific LC/MS analytical method, which utilized electrospray ionization.


RESULTS
The bioavailability of orally administered BMABO was determined by comparing plasma concentrations after oral gavage delivery with intravenous delivery. Following delivery of the oral dose, the average C (max) was 1,710 +/- 503 ng/ml, and the AUC-value was found to be 3,561 +/- 670 ng min kg/ml mg. Relative to the intravenous dose (100% bioavailability), the bioavailability was 6.2% after oral administration.


CONCLUSIONS
As the current studies demonstrate the novel radio-sensitization agent BMABO may have potential therapeutic valuable in cancer treatment. Further evaluation of the efficacy and toxicity of BMABO will determine the feasibility of the oral route for future clinical studies.
Al-Ghananeem
Abeer M
AM
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
Albayati
Zaineb F
ZF
Malkawi
Ahmad
A
Sonar
Vijayakumar N
VN
Freeman
Michael L
ML
Crooks
Peter A
PA
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D014018:Tissue Distribution
C524119:2-(1-benzylindole-3-ylmethylene)azabicyclo(2.2.2)octane-3-ol; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011838:Radiation-Sensitizing Agents