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目的考察单次静脉注射和口服给予大鼠2,3-吲哚醌后的药代动力学,为该药的新药开发提供依据。方法大鼠给药后经眼眶静脉采大约0.25ml血液,采集时间点为:给予受试物前(0hr)和给予受试物后5、15、30min、1、2、4、6、8h和24h。血液样本采集后置于冰上,并立即取出50μl全血采用甲醇蛋白沉淀进行预处理,奎硫平作为内标。预处理后样品采用LC/MS/MS法进行测定,并用药动学处理软件WinNonlin5.2采用非房室模型计算相关药代动力学参数。结果 SpragueDawley大鼠静脉注射和口服两种制剂的药动学参数(平均值±标准偏差)如下。静脉注射:Tmax为(0.83±0.29)hr,Cmax为(141.53±10.99)μg/L,t1/2为(1.68±0.84)hr,AUC0-t为(1068.15±389.06)μg/hr/L,AUC0-∞为(1211.19±469.18)μg·hr/L,Vz为(4.13±1.41)L/kg,CLz为(1.89±0.94)L/hr/kg;口服:Tmax为(0.05±0.00)hr,Cmax为(1725.53±469.70)ng/ml,t1/2为(4.21±2.78)hr,AUC0-t为(7711.21±2533.12)μg/hr/L,AUC0-∞为(7986.07±2623.38)μg/hr/L,以AUC0-t计算,生物利用度平均为(57.75±18.97)%。结论 2,3-吲哚醌大鼠体内消除较快,可能存在非线性消除,口服吸收较好。
Objective To investigate the pharmacokinetics of 2,3-indoquinone in rats after a single intravenous injection and oral administration, providing a basis for the development of new drugs. Methods Approximately 0.25 ml of blood was collected via the orbital vein after administration to rats. The time points were (0 hr) and 5, 15, 30 min, 1, 2, 4, 6, 24h. Blood samples were collected and placed on ice, and 50 μl of whole blood was immediately removed and pre-treated with methanol-protein precipitation. Quetiapine was used as an internal standard. After pretreatment samples were determined by LC / MS / MS method, and pharmacokinetic software WinNonlin5.2 using non-compartmental model to calculate the relevant pharmacokinetic parameters. Results The pharmacokinetic parameters (mean ± standard deviation) of the two formulations of SpragueDawley rats intravenously and orally were as follows. Intravenous injection: Tmax was (0.83 ± 0.29) hr, Cmax was (141.53 ± 10.99) μg / L, t1 / 2 was 1.68 ± 0.84 hr, AUC0-t was 1068.15 ± 389.06 μg / hr / -∞ was (1211.19 ± 469.18) μg · hr / L, Vz was (4.13 ± 1.41) L / kg and CLz was (1.89 ± 0.94) L / hr / kg respectively. Oral: Tmax was (0.05 ± 0.00) Was (1725.53 ± 469.70) ng / ml, t1 / 2 was (4.21 ± 2.78) hr, AUC0-t was (7711.21 ± 2533.12) μg / hr / L and AUC0- ∞ was (7986.07 ± 2623.38) μg / hr / L , With AUC0-t calculation, the average bioavailability was (57.75 ± 18.97)%. Conclusion 2,3-indolquinone in rats to eliminate faster, there may be non-linear elimination, oral absorption is better.