微透析法研究罗通定经皮给药在大鼠体内不同部位的浓度分布

Distribution of rotundine concentrations at various sites in rats following transdermal administration studied by microdialysis

目的研究罗通定经皮给药后,药物在大鼠脑、皮下、血管3个部位微透析液和尾静脉血浆的浓度变化。方法采用微透析技术取样,HPLC测定不同时间点大鼠脑、皮下、血管的微透析液的药物浓度以及尾静脉血浆的药物浓度,DAS 2.0药动学软件计算药动学参数。结果罗通定20 cm2经皮给药后,在大鼠体内消除缓慢,脑、皮下、血管和血浆AUC0→10h分别为(387.19±162.81)、(245.97±74.60)、(211.41±65.19)和(1 677.05±598.83)min·mg·L-1。体内药物含量血浆中最高,脑微透析次之,血管微透析最低,经皮给药后的AUC脑/AUC血浆、AUC皮下/AUC血浆、AUC血管/AUC血浆分别为(23.45±6.51)%、(15.66±5.03)%和(13.87±5.84)%。结论微透析法能很好地应用于罗通定经皮给药后大鼠不同部位的浓度研究,反映脑、皮下和血管之间的关系。

AIM To investigate and compare the concentration variation of rotundine in brain microdialysis, subcutaneous microdialysis, vascular microdialysis and plasma after transdermal administration in rats. METHODS The concentrations of rotundine were determined by HPLC while the pharmacokinetic parameters were calculated by DAS 2.0 software. RESULTS The distribution and elimination of rotundine were slow. After 20 cm^2 transdermal administration of rotundine in rats, the main pharmacokinetic parameters （AUC0→10 h） of brain, subcutaneous, vascular and plasma were as follows： （387.19± 162.81）, （245.97± 74.60） concentration of rotundine in plasma was higher than , （211.41 ± 65.19） and （1 677.05± 598.83） min·mg·L^-1 . The that in brain microdialysis, and the latter was higher than that in blood and skin microdialysis. The ratios of AUCbrain/AUCplasma, AUCsubcutaneous /AUCplasma, and AUCvascular/AUCplasma were （23.45 ±6.51） %, （15.66 ± 5.03）%, and （13.87 ± 5.84）%, respectively. CONCLUSION Microdialysis could be used to study concentration of rotundine following transdermal administration at various sites in rats to illustrate the relationships among brain, subcutaneous and vascular.