Zhang Yanhui,Yu Chao,Guo Yanlei,Zhang Youjin,Li Wenjuan,Yang Zhu,Wang Yingxiong.Astragaloside Ⅳ exerts drug interactions via inhibiting CYP1A2 activity in rats[J].J Amry Med Univ (J Third Mil Med Univ),2012,34(13):1300-1303.
Zhang Yanhui,Yu Chao,Guo Yanlei,Zhang Youjin,Li Wenjuan,Yang Zhu,Wang Yingxiong.Astragaloside Ⅳ exerts drug interactions via inhibiting CYP1A2 activity in rats[J].J Amry Med Univ (J Third Mil Med Univ),2012,34(13):1300-1303.DOI:
Astragaloside Ⅳ exerts drug interactions via inhibiting CYP1A2 activity in rats
Objective To determine the effect of astragaloside Ⅳ (AGS-Ⅳ) on the activity of CYP1A2 in rats to elucidate the possibility CYP1A2-induced interactions of drugs. Methods Analysis of theophylline
and acetamidophenol (internal standard) was achieved using waters C
18
column (250 mm×4.6 mm×5 μm) and a mobile phase consisted of methanol-water (17∶83
v/v) was delivered at a flow rate of 1.0 ml/min at 30 ℃ at a wavelength of 274 nm. Seven rats were divided into 2 groups by simple rand
om sampling. Three rats were intravenously treated with AGS-Ⅳ (3 mg/kg)
and the left 4 rats were intravenously administered with an equivalent volume of 0.1% DMSO vehicle once a day for a week. On the eighth day
all of the rats were intragastrically administered theophylline. The concentration of theophylline in the plasma was determined by high performance liquid chromatography (HPLC). The distinction of pharmacokinetic parameters was compared to investigate the effect of AGS-Ⅳ on the activity of CYP1A2. Results Theophylline and acetamidophenol were separated well
the detection limit of theophylline was 80 nmol/L
and the linear rang of our method was 0.2 to 50 μmol/L. The intra-day and inter-day relative standard deviations were both less than 10%
and the recoveries were more than 91. The main pharmacokinetic parameters of area under the concentration-time cure (AUC) of theophylline were higher than control groups (131.16±3.22 vs 97.51±6.40). The apparent oral total body clearance value (CL/F) of test group and control group were 0.12±0.01 and 0.17±0.02 respectively
with the former obviously lower than the latter (P0.05). Conclusion AGS-Ⅳ exerts obvious inhibitory effect on CYP1A2 activity in rats
so its should be cautious to co-administer with drugs metabolized by CYP1A2.