Effects of Glycyrrhizic Acid on Pharmacokinetics of Nifedipine in Rats
- VernacularTitle:甘草酸对大鼠体内硝苯地平药动学的影响
- Author:
Jun MAO
1
,
2
;
Xiangyu ZHU
1
;
Hongguang XIA
1
;
Zhihao WANG
1
;
Huiru LIU
2
;
Haiyan JIANG
1
;
Yong JIN
1
Author Information
1. Key Lab of Anti-inflammatory and Immune Medicine，Ministry of Education，School of Pharmacy，Anhui Medical University，Hefei 230032，China
2. Dept. of Pharmacy，Hefei Second People’s Hospital，Hefei 230026，China
- Publication Type:Journal Article
- Keywords:
Glycyrrhizic acid;
Nifedipine;
Diazepam;
HPLC;
Pharmacokinetics;
Rat
- From:
China Pharmacy
2019;30(21):2942-2945
- CountryChina
- Language:Chinese
-
Abstract:
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.
