Establishment and verification of cytochrome P450 3 A enzyme induction model in female rats / 中国药学杂志

OBJECTIVE: To establish a female rat CYP3A induction model which is used for studying CYP3A-mediated drug-drug interactions. METHODS: Female SD rats which were fed with standard diet were randomly divided into two groups, one was the control group, and the other one was the experimental group. The rats in the experimental group were administered respectively 20, 50, 80, 100, and 150 mg·g-1d-1 dexamethasone by gavage for 3 d to induce CYP3A enzymes. 24 h after 3 d, liver tissues were taken from both groups of rats and rat liver microsomes were prepared. CYP3A4 activity was determined with testosterone as the probe substrate. RESULTS: Testosterone metabolic rate was 31.68% in blank liver microsomes, and were 40.64%, 61.36%, 82.44%, 85.8%, and 83.36% in dexamethasone-induction group. Testosterone metabolic rate was improved by up to 160.23% after dexamethasone induction at 80 mg·g-1d-1 in female rats. CONCLUSION: Dexamethasone induction at 80 mg·g-1d-1 can significantly increase liver CYP3A enzyme activity in female SD rats, and the model can be used to study CYP3A-mediated drug-drug interactions.

Pharmacokinetics of luteolin from Elsholtzia blanda extracts in rats / 药学学报

An RP-HPLC method for determination of luteolin from Elsholtzia blanda Benth. extracts in rats' plasma was established and the pharmacokinetics of luteolin in rats was studied. Drug blood samples from caudal vein were gotten after oral administration of luteolin. Plasma samples were determined by RP-HPLC after being deproteinized with trichloroacetic acid and extracted with ethyl acetate. The calibration curve was linear in the range of 0.37-47.27 microg x mL(-1). The limit of quantification was 0.37 microg x mL(-1). The method recovery of luteolin was 93%-99%. The extract recovery was 75%-85%. RSDs of intra-and inter-day precisions were less than 5%. The concentration-time curve of luteolin after oral administration of Elsholtzia blanda Benth. extracts was fitted to two compartment open model. Two factors analysis of variance were adopted in the evaluation of gender and time spots for collection of blood. The result suggested that the gender-based difference in blood-drug concentrations had statistical significance. The metabolite in blood was identified as galcuronide. The method is sensitive, specific, accurate, and is appropriate for determination of luteolin in vivo.

Interaction between (E)-2-(4-(diethylamino methyl) benzylidene)-5,6-dimethoxy-2,3-dihydroinden-one and P-glycoprotein / 药学学报

Cell lines of Bcap37 and Bcap37/MDR1 (the high P-glycoprotein (P-gp) expressing cell line) were used as model to investigate the different accumulations of (E)-2-(4-(diethylamino methyl) benzylidene)-5,6-dimethoxy-2,3-dihydroinden-one (BYZX) in the two kinds of cells. It was authenticated that whether BYZX was the substrate of P-gp. Meanwhile, the inhibitive effects of BYZX on the P-gp were investigated by determining the fluorescence intensity of rhodamine 123 in the model cells, with and without BYZX. A reversed-phase high-performance liquid chromatography (RP-HPLC) method was used to determine the accumulations of BYZX in the two cells. The results showed that the amount of BYZX accumulation in Bcap37/MDR1 cells were as many as those in Bcap37 cells (P > 0.05), and the concentrations of BYZX accumulated in the Bcap37/MDR1 cells did not increase when co-incubated with P-gp inhibitor verapamil. Furthermore, different concentrations of BYZX also had no effects on the efflux of rhodamine 123 (P > 0.05). These results indicated that there were no interactions between BYZX and P-gp. BYZX will not be pumped out of the cells, and it also not inhibited the P-gp. It was the useful advantage for its absorption.