盐酸他可林在不同月龄大鼠体内的药物动力学比较

Comparision of pharmacokinetics of tacrine between young rats and aged rats

目的 研究并比较盐酸他可林（ＴＨＡ）在不同月龄大鼠体内的药物动力学。方法 青年大鼠和老龄大鼠分别ｉｖ和 ｉｇ ＴＨＡ ８ｍｇ／ｋｇ后，定时采血，用反相高效液相色谱法测定血药浓度，计算机拟合房室模型，并计算药动学参数。结果 两种大鼠静注或灌胃给药后，血药浓度－时间关系符合二室模型；老龄大鼠大多数时间声、的血药浓度显著高于青年大鼠；老龄大鼠静注的药动学参数Ｔ１／２α、Ｔ１／２β部和ＡＵＣ分别比青年大鼠大８０％、６３％和６２％；而灌胃时Ｔ１／２α、Ｔ１／２β、ＡＵＣ。Ｃｍ和Ｔｐ分别比青年大鼠大２９％。５６％、１００％、６８％和２１％，两种动物相比有显著性或非常显著性差异（Ｐ＜０．０５或 Ｐ＜ ０．０１）。结论 ＴＨＡ在老龄大鼠的吸收、分布，尤其是消除明显比青年大鼠慢。

Aim To compare the pharmacokinetics of tacrine (THA) between young rats and aged rats. Methods After ig and iv THA 8 mg/ kg, the plasma THA concentrations in rats were de termined by reversed phase HPLC. The compartment model and the pharmacokinetic parameters were calculated by CAPP software. Results The concentration - time curve was de- scribed by a two - compartment open model. The concentrations of THA in aged rats were much higher than those in normal rats. After iv administration, the main pharmacokinetic paramaters in young rats such as T1/2α, Tl/2β and AUC were 10 ± 6 mm, 60 ± 6 mm, and 34±13 g/ min·L, while those in aged rats were 18±3 min, 98±19 min, and 55±7 g/ min·L, re- spectively. After ig THA, the values of T1/2α , T1/2β, AUC, Cm and Tp in young rats were 7 ± 2 min, 63 ± 8 min, 12 ± 5 g/ min·L, 130± 58 μg/ L, and 19 ± 2 min , while those in aged rats were 9±1 min, 98± 28 min, 24±10 g/min· L, 218± 72 μg/L, 23±2 mm, respectively. The parameters were significant differences between the two kinds 0r rats (P< 0.05 or P< 0.01). Conclusion The absorption, distribution and elimination of THA in aged rats were slower than those in young rats.