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

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.