Effect of cooperation between transporters and metabolic enzymes on drug disposition by intestine and liver / 药学学报

Drug transporters and metabolic enzymes are the key proteins in the disposition of drugs in the body. In recent years it has been found that there is a cooperative relationship between drug transporters and metabolizing enzymes. Functional changes in drug transporters or metabolizing enzyme can affect the ability to eliminate drugs. Therefore, it is important to clarify this cooperative relationship, which is directly related to the pharmacokinetics, pharmacodynamics and adverse effects of drugs. Intestine and liver are the main organs of drug metabolism. There are abundant drug transporters and metabolizing enzymes in the tissues. This paper reviews the influence of the cooperative relationship between drug transporters and metabolizing enzymes on drug disposition by intestine and liver.

Screening for potential bioactive components of Yin-zhi-huang using high bilirubin HepaRG cells incubating with serum from animals / 药学学报

A hyper-bilirubin cell model was established for its relevance to the pathological state of jaundice in human. This model was used to screen for the pharmacological components of Yin-Zhi-huang (YZH). Total bilirubin, indirect bilirubin in cells, and direct bilirubin in extracellular fluid were quantified after HepaRG cells were incubated with serum from rats injected with multiple components of YZH. Cellular uptake was determined by dynamic multiple reaction monitoring (DMRM) using LC-MS/MS. We found that the stable hyper-bilirubin HepaRG cell model could be established by incubating cells with 40 μg·mL-1 bilirubin and 50 μg·mL-1 probenecid. When the hyper-bilirubin cell model was incubated with serum from rats of YZH injection, there were 52.4% and 60.1% decrease in intercellular total bilirubin and indirect bilirubin, respectively, and 52.5% increase in extracellular direct bilirubin. Using DMRM mode, 53 components could be determined, and 8 potential bioactive candidates were identified from the serum. This method could be used to screen for bioactive metabolites of YZH. This strategy is simple, highly active, sensitive and specific, providing a new method for high throughput screening of therapeutic or toxic metabolites from traditional Chinese medicine. The regulations of Ethics Committee in the First Hospital of Lanzhou University were abided in the rat experiment of this study.

Effects of metoprolol or/and pravastatin on the pharmacokinetics of metformin in rats / 药学学报

This study investigates the effects of metoprolol (METO) or/and pravastatin (PRAV) on the pharmacokinetics of metformin (METF) in rats. Twenty-eight male SD rats were divided into METF group, METF+METO group, METF+PRAV group and METF+METO+PRAV group. Blood samples were collected at 10, 20, 40, 60, 90, 120, 180, 240, 360, 480 and 600 min after oral administration of metformin, and concentration of metformin in plasma was determined by HPLC. Compared to the METF group, Cmax of metformin was significantly decreased (P0-t, t1/2 and V were significantly increased in the METF+METO group; t1/2 was significantly decreased in the METF+PRAV group; Cmax was significantly decreased and MRT0-t was significantly increased in the METF+METO+PRAV group. Compared to the METF+METO group, MRT0-t of metformin was significantly decreased in the METF+METO+PRAV group. Compared to the METF+PRAV group, Cmax of metformin was significantly decreased (P0-t, t1/2 and V were significantly increased in the METF+METO+PRAV group. There exist multiple drug interactions of metformin, metoprolol and pravastatin in rats.

Study of pharmacokinetics of digoxin in ovariectomized rats model / 药学学报

This study aims to investigate the change of plasma concentration of digoxin (DIG) in rats with ovariectomy. Twelve female SD rats were randomly assigned into ovariectomized group and sham group (n = 6). All rats plasma was collected after a single dose of 2 mg x kg(-1) DIG administrated orally, serum DIG concentration was determined by LC-MS/MS. The level of P-gp in the intestinal was analyzed by Western blotting. Pharmacokinetic calculations were performed on each individual using DAS 2.0 practical pharmacokinetic software. Compared with the sham group, C(max) of ovariectomized group decreased significantly (P < 0.01). There was no significant difference of AUC(0-t), and the level of P-gp was elevated in ovariectomized group. It was found that C(max) of DIG was significantly reduced after ovariectomy, and the change was associated with the decreased level of estrogen, which contributes to the increased level of P-gp.

Simultaneous determination of repaglinide and pravastatin sodium in rat plasma by LC-ms/MS and its application on pharmacokinetic interactions study / 药学学报

The study aims to establish a method for simultaneous determination of repaglinide and pravastatin sodium in rat plasma by LC-MS/MS and to study its pharmacokinetic interactions. Eighteen male SD rats were divided into repaglinide group, pravastatin sodium group and co-administration group. Blood samples were collected at different times after oral administration. Repaglinide and pravastatin sodium in rat plasma were separated by Agilent HC-C18 with the mobile phase consisting of methanol-0.1% formic acid (80 : 20). Detection and quantification were performed by using ESI-MS. The detector was operated in selected Reaction-monitoring mode at m/z 453.3-->230.1 for repaglinide, m/z 447.2-->327.4 for pravastatin sodium and m/z 285.1-->192.9 for diazepam as the internal standard. The calibration curve obtained was linear (R2>0.99) over the concentration range of 9.77-10,000 ng.mL-1 for repaglinide and 4.88-625 ng.mL-1 for pravastatin sodium. Compared with the single administration group, Cmax and AUC0-6h of repaglinide increased significantly (P<0.05) and tmax of pravastatin sodium prolonged (P<0.05) in co-administration group. The method is found to be simple, sensitive and accurate for determining the concentration of repaglinide and pravastatin sodium in rat plasma. There exists pharmacokinetic interactions in the co-administration of repaglinide and pravastatin sodium.

Pharmacokinetic variation of ofloxacin based on gender-related difference in the expression of multidrug resistance-associated protein (Abcc2/Mrp2) in rat kidney / 药学学报

The present study aimed to investigate the pharmacokinetic variation of ofloxacin based on gender-related difference in the expression of multidrug resistance-associated protein (Abcc2/Mrp2) in rat kidney. The concentrations of ofloxacin in rat plasma and urine were determined after tail vein administration (30 mg x kg(-1)) by high-performance liquid chromatography (HPLC) method. Expression of Mrp2 in kidney of male and female rats was qualitatively and quantitatively detected by immunohistochemistry and flow cytometry, separately. The results showed that AUC value of ofloxacin was lower in male rats than that in female rats and the total amount of ofloxacin excreted in the urine was higher in male rats than that in female rats. And the expression of Mrp2 in male rat kidney was higher than that in female rats. All results suggested that gender-related differences in pharmacokinetics of ofloxacin may be attributed to the differences in the expression of Mrp2 in kidney of male and female rats.

Effects of Yuquan pills on pharmacokinetics of metformin hydrochloride in diabetic rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study effects of Yuquan pills on the pharmacokinetics process of metformin hydrochloride in diabetic rats.</p><p><b>METHOD</b>After administration Yuquan pills 7 day to the diabetic rats, the metformin hydrochloride was orally administrated, then the blood samples were collected at different time. The concentrations of metformin hydrochloride in plasma were determined by HPLC method and the pharmacokinetic parameters were calculated.</p><p><b>RESULT</b>The pharmacokinetic parameter Cmax of the controlling group and the testing group were respectively, 18.95, 21.76 mg x L(-1); t1/2 were 1,069.8, 1,767.4 min, respectively; CL/F were 0.013, 0.008 L x min(-1) x kg(-1); AUC were 10,042.1, 10,712.2 mg z L(-1) x min(-1) respectively.</p><p><b>CONCLUSION</b>The pharmacokinetics process of metformin hydrochloride in diabetic rats fits one-compartment model. Yuquan pills has a significant effect on the pharmacokinetics of metformin hydrochloride in diabetic rats.</p>

Isolation and indentification of chemical compounds from Drynaria fortunei / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical components of Drynaria fortunei.</p><p><b>METHOD</b>The herbal material was extracted with 75% ethanol. The chemical components were isolated by silica gel and sephadex LH-20 column chromatography. The structures were identified on the basis of chemical and spectroscopic data.</p><p><b>RESULT</b>Four compounds were isolated, three of which were identified as (-)-epiafzelechin-3-O-beta-D-allopyranoside, (-)-epiafzelechin and beta-sitosterol.</p><p><b>CONCLUSION</b>(-)-epiafzelechin-3-O-beta-D-allopyranoside, (-)-epiafzelechin were obtained from D. fortunei for the first time.</p>

Opinion of colon-targeting delivery about rhubarb extract as a purgative / 中国中药杂志

<p><b>OBJECTIVE</b>To elucidate that rhubarb extract as a purgative should be delivered to colon from a pharmaceutical point of view.</p><p><b>METHOD</b>Effects of anthranoids and free anthraquinones as purgatives on the colon motility and transit time, the absorption in vivo, and the loss in the processes of extraction, concentration and dryness were reviewed, based on the recent 60 years pharmacological, pharmaceutical and clinical experimental studies at home and abroad.</p><p><b>RESULT AND CONCLUSION</b>Free anthraquinones in rhubarb extract should be regarded as purgative principles. Close attention should be paid to the loss of free anthraquinones not only in the processes of extraction, concentration and dryness, but also in the process of transit in the upper gastrointestinal tract. Colon-targeting delivery of rhubarb extract, as a purgative, may prevent absorption of free anthraquinones in the upper gastrointestinal tract, thus improving clinical effects and lowering dosage.</p>

Pharmacodynamic Comparison between Fast-disintegrating Oral Nitroglycerin Tablets and Commercial Tablets / 中国药房

OBJECTIVE:To evaluate clinical pharmacodynamics between fast-disintegrating oral nitroglycerin tablets and commercial tablets.METHODS:Fast-disintegrating oral nitroglycerin tablets with the same content as commercial tablets were prepared,the effects of two kinds of tablets on diastolic blood pressure,heart rate of the healthy volunteers were observed and compared.RESULTS:Fast-disintegrating oral nitroglycerin tablets showed more rapid drug absorption than the commercial tablets3minutes after administration,there was remarkable difference between them(P