BNOAT Oncology, Inc, Akron Innovation Campus, Akron, OH, USA.
Anticancer Res. 2012 Sep;32(9):3749-52.
BACKGROUND/AIM: Nitrosylcobalamin (NO-Cbl) is a cobalamin-based anti-tumor agent. This study evaluated the pharmacokinetic parameters of NO-Cbl following intravenous administration in dogs.
Four dogs received 10 mg/kg, 20 mg/kg and 40 mg/kg intravenous bolus doses of NO-Cbl, with a 14-day washout period between doses. Blood samples were collected at baseline and post-dosing, and noncompartmental pharmacokinetic parameters were determined.
Average peak serum concentrations of 2265, 5523 and 13,866 pg/mL were achieved following single-dose bolus intravenous administration of 10 mg/kg, 20 mg/kg and 40 mg/kg of NO-Cbl respectively. The average area under the curve was 12,697 h × pg/mL, 24,497 h × pg/mL and 44,976 h × pg/mL respectively, with an average elimination half-life of 16.2 h, 13.5 h and 13.1 h respectively.
These results can be used to determine the dose and dosing intervals for clinical trials evaluating NO-Cbl in humans and companion animals.
背景/目的：硝基亚钴胺素（NO-Cbl）是一种基于钴胺素的抗肿瘤药物。本研究评估了犬静脉注射 NO-Cbl 后的药代动力学参数。
4 只狗分别接受了 10 mg/kg、20 mg/kg 和 40 mg/kg 的静脉推注剂量的 NO-Cbl，两次剂量之间有 14 天的洗脱期。在基线和给药后采集血样，并确定非房室药代动力学参数。
单次静脉推注 10 mg/kg、20 mg/kg 和 40 mg/kg 的 NO-Cbl 后，平均血清峰浓度分别为 2265、5523 和 13866 pg/mL。平均曲线下面积分别为 12697 h×pg/mL、24497 h×pg/mL 和 44976 h×pg/mL，平均消除半衰期分别为 16.2 h、13.5 h 和 13.1 h。
这些结果可用于确定在人类和伴侣动物中评估 NO-Cbl 的临床试验的剂量和给药间隔。
