A pharmacokinetic study on Z-(+/-)-2-(1-benzylindole-3-yl-methylene)azabicyclo[2.2.2]octane-3-ol; a novel radio-sensitization agent.

Al-Ghananeem AM, Albayati ZF, Malkawi A, Sonar VN, Freeman ML, Crooks PA
Cancer Chemother Pharmacol. 2007 60 (6): 915-9

PMID: 17294191 · DOI:10.1007/s00280-007-0425-8

PURPOSE - 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.

CONCLUSION - 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.

MeSH Terms (15)

Administration, Oral Animals Area Under Curve Biological Availability Bridged Bicyclo Compounds, Heterocyclic Chromatography, Liquid Dose-Response Relationship, Drug Half-Life Injections, Intravenous Male Radiation-Sensitizing Agents Rats Rats, Sprague-Dawley Spectrometry, Mass, Electrospray Ionization Tissue Distribution

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