线性探针微透析研究阿魏酸经皮给药后药动学

Pharmacokinetics of ferulic acid in transdermal delivery

目的:建立线性探针测定阿魏酸皮下浓度方法,考察温度、灌流液流速、浓度对线性探针回收率的影响,研究阿魏酸溶液经皮给药后体内药动学。方法:采用减量法测定阿魏酸线性探针的体内外回收率的稳定性,采用增量法测定体外回收率的影响因素,选择CD-1裸鼠作为实验动物,采用经皮微透析法进行体内药动学研究,HPLC测定透析液中阿魏酸的浓度。结果:温度对阿魏酸体外回收率有显著性影响,随着温度的升高,阿魏酸的体外回收率显著提高,随着流速的增加阿魏酸的体外回收率呈指数下降,在测定范围内,浓度对阿魏酸的体内外回收率无影响,在测定时间内阿魏酸体内外回收率稳定性、重复性良好,体外平均回收率为(24.82±1.01)%;体内平均回收率为(16.50±1.92)%;经皮给药后,阿魏酸86 min达到峰值,平均滞留时间为291 min。结论:线性探针可用于阿魏酸经皮给药的研究;阿魏酸可迅速透过角质层,适宜制成经皮给药制剂。

Objective： To study the pharmacokinetics of ferulic acid in transdermal delivery; the influence factors such as tem- perature, flow rate, and drug concentration on the probe recovery are also investigated to obtain accurate data. Method： The stability of in vitro and in vivo recovery was determined by loss but the influence factor on the recovery was determined by gain. Appling dermal mierodialysis to ferulic acid analytes, the concentration of ferulic acid in the dialysate was detected by HPLC. Result： There is a sig- nificant effect on the probe recovery for the in vitro recovery is much bigger at a higher temperature. When the flow rate rises, the in vitro recovery is down at index rate instead. Within the measuring rage, the drug concentration doesn＇t have effect on the recovery. The steady and reproduce of recovery is well within the measuring time, and the average recovery of in vitro is （ 24. 82 ± 1.01 ） % without temperature control and in vivo is （ 16. 50 ± 1.92） %. The Cmax of ferulie acid is 86 min and MRT is 291 min after dermal administra- tion. Conclusion： Dermal mierodialyis can be used in the ferulie acid study. For the ferulic acid can permeate the corneum quciky, it is practical to develop a transdermal delivery.