浏览全部资源
扫码关注微信
目的:研究甘草酸对大鼠体内硝苯地平药动学的影响。方法:将大鼠随机分为实验组和对照组,每组10只。实验组大鼠灌胃甘草酸5 mg/kg,对照组灌胃等量的0.5%羧甲基纤维素钠溶液,每日1次,连续给药14 d,第14天灌胃30 min后,2组大鼠均灌胃硝苯地平3 mg/kg,并于灌胃硝苯地平前与灌胃后0.25、0.5、0.75、1、1.5、2、3、4、6、8、12、24 h眼内眦静脉丛采血0.5 mL。采用高效液相色谱法,以地西泮为内标,测定其中硝苯地平的浓度;色谱柱为ODS-C18;流动相为甲醇-水(62 ∶ 38,V/V,乙酸调pH为4.5);流速为1.0 mL/min;柱温为30 ℃;检测波长为238 nm;进样量为20 μL。使用Winonlin 6.0软件计算药动学参数,t检验进行统计分析。结果:实验组和对照组大鼠体内硝苯地平的主要药动学参数tmax分别为(1.40±0.15)、(1.50±0.01) h;cmax分别为(0.15±0.03)、(0.29±0.09) mg/L;t1/2分别为(4.70±1.17)、(5.20±1.38) h;AUC0-24 h分别为(1.00±0.10)、(1.89±0.37) mg·h/L;AUC0-∞分别为(1.00±0.16)、(1.98±0.32) mg·h/L;MRT分别为(6.76±0.64)、(6.60±1.36) h。与对照组比较,实验组大鼠体内硝苯地平的cmax、AUC0-24 h、AUC0-∞均明显降低,差异具有统计学意义(P<0.05)。结论:甘草酸可能会降低硝苯地平在大鼠体内的生物利用度,两药联用时建议增加硝苯地平的剂量以达到有效的血药浓度。
OBJECTIVE: To study the effects of glycyrrhizic acid on the pharmacokinetics of nifedipine in rats. METHODS: Rats were randomly divided into experimental group and control group, with 10 rats in each group. Experimental group was given glycyrrhizic acid 5 mg/kg and control group was given 0.5% CMC-Na (sodium carboxymethylcellulose) solution, once a day, for 14 consecutive days. On 14th day after 30 min of intragastric administration, both groups were given nifedipine 3 mg/kg intragastrically. Blood samples 0.5 mL were collected from intraocular vein plexus before and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h after intragastric administration. The concentration of nifedipine was determined by HPLC using diazepam as internal standard. The determination was performed on ODS-C18 column with mobile phase consisted of methanol-water (62 ∶ 38, V/V,pH adjusted to 4.5 with acetic acid) at the flow rate of 1.0 mL/min. The column temperature was 30 ℃. The detection wavelength was set at 238 nm, and sample size was 20 μL. The pharmacokinetic parameters were calculated with Winonlin 6.0 software, and statistical analysis was performed by t-test. RESULTS: The main pharmacokinetic parameters of the experimental group and the control group were as follows as tmax was (1.40±0.15), (1.50±0.01) h; cmax was (0.15±0.03), (0.29±0.09) mg/L; t1/2 was (4.70±1.17), (5.20±1.38) h; AUC0-24 h were (1.00±0.10), (1.89±0.37) mg·h/L; AUC0-∞ was (1.00±0.16), (1.98±0.32) mg·h/L; MRT was (6.76±0.64), (6.60±1.36) h, respectively. Compared with control group, cmax, AUC0-24 h and AUC0-∞ of nifedipine were decreased significantly in experimental group, with statistical significance (P<0.05). CONCLUSIONS: Glycyrrhizic acid can reduce the bioavailability of nifedipine in rats. It is suggested that the dosage of nifedipine should be increased in order to achieve effective blood concentration.
甘草酸硝苯地平地西泮高效液相色谱法药动学大鼠
Glycyrrhizic acidNifedipineDiazepamHPLCPharmacokineticsRat
0
浏览量
3
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构