Al-Ghananeem Abeer M, Albayati Zaineb F, Malkawi Ahmad, Sonar Vijayakumar N, Freeman Michael L, Crooks Peter A
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
Cancer Chemother Pharmacol. 2007 Nov;60(6):915-9. doi: 10.1007/s00280-007-0425-8. Epub 2007 Feb 9.
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.
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.
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.
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.
本研究旨在表征新型放射增敏剂Z-(+/-)-2-(1-苄基吲哚-3-基亚甲基)氮杂双环[2.2.2]辛烷-3-醇（BMABO）口服给药后的药代动力学参数并评估其绝对生物利用度。
将20mg/kg的单一口服剂量给予Sprague-Dawley大鼠，并与该化合物静脉注射给药（1mg/kg）进行比较。在不同时间点采集血样，使用一种新的灵敏且特异的液相色谱/质谱分析方法（利用电喷雾电离）测定血浆中BMABO的浓度。
通过比较口服灌胃给药和静脉给药后的血浆浓度来确定口服BMABO的生物利用度。口服给药后，平均C(max)为1710±503ng/ml，AUC值为3561±670ng·min·kg/ml·mg。相对于静脉给药剂量（生物利用度100%），口服给药后的生物利用度为6.2%。
正如当前研究所表明的，新型放射增敏剂BMABO在癌症治疗中可能具有潜在的治疗价值。对BMABO的疗效和毒性进行进一步评估将确定口服途径在未来临床研究中的可行性。
