Effect of Green Tea and (-)-Epigallocatechin Gallate on the Pharmacokinetics of Rosuvastatin

2020 ◽  
Vol 21 (6) ◽  
pp. 471-478
Author(s):  
Shenjia Huang ◽  
Qingqing Xu ◽  
Linsheng Liu ◽  
Yicong Bian ◽  
Shichao Zhang ◽  
...  
Keyword(s):  
Green Tea ◽  
Cell Model ◽  
Hek293t Cell ◽  
Epigallocatechin Gallate ◽  
Drug Uptake ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Sprague Dawley ◽  
Time Curve ◽  
Uptake And Transport

Background: Green tea can inhibit OATPs, so it may interact with the substrate of OATPs, such as rosuvastatin. Objective: This study aimed to investigate the effects of green tea on the pharmacokinetics of rosuvastatin and its mechanism. Methods: Male Sprague-Dawley rats received different doses of green tea extract (GTE) and (-)- epigallocatechin-3- gallate (EGCG). Caco-2 cells and OATP1B1-HEK293T cells were used in drug uptake and transport assay. The matrix concentrations of rosuvastatin and catechins were determined by ultra-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS). Results: GTE and EGCG were both found to increase the area under the plasma concentration-time curve (AUC0-∞) of rosuvastatin ((p<0.050). In the Caco-2 cell model, the uptake and transport of rosuvastatin in the GTE groups were 1.94-fold (p<0.001) and 2.11-fold (p<0.050) higher, respectively, than those of the control group. However, in the EGCG group, the uptake and transport of rosuvastatin were decreased by 22.62% and 44.19%, respectively (p<0.050). In the OATP1B1- HEK293T cell model, the OATP1B1-mediated rosuvastatin uptake was decreased by GTE to 35.02% of that in the control (p<0.050) and was decreased by EGCG to 45.61% of that in the control (p<0.050). Conclusion: GTE increased the systemic rosuvastatin exposure in rats. The mechanism may include an increase in rosuvastatin absorption and a decrease in liver distribution by inhibiting OATP1B1. EGCG may be the main ingredient of green tea that affects the pharmacokinetic parameters of rosuvastatin. Our results showed the importance of conducting green tea-rosuvastatin study.

scholarly journals Assessment of Liver Function Using Pharmacokinetic Parameters of Gd-EOB-DTPA: Experimental Study in Rat Hepatectomy Model

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Myung-Won You ◽  
Hyoung Jung Kim ◽  
Hyeong-Seok Lim ◽  
So Yeon Kim ◽  
Jae Ho Byun ◽  
...  
Keyword(s):  
Liver Function ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Sprague Dawley ◽  
Time Curve ◽  
Blood Samples ◽  
The Difference ◽  
Hepatectomy Group ◽  
Group Comparisons

Objectives. To determine whether the pharmacokinetic parameters of Gd-EOB-DTPA can identify the difference in liver function in a rat hepatectomy model. Methods. A total of 56 eight-week-old male Sprague-Dawley rats were divided into the following groups: control group without hepatectomy (n=16), 70% hepatectomy group (n=14), and 90% hepatectomy group (n=26). On postoperative day 2, Gd-EOB-DTPA (0.1 mmol/kg) was injected intravenously and serial blood samples were obtained. Pharmacokinetic analysis was performed using a noncompartmental method. Statistical analysis was performed using one-way analysis of variance and post hoc pairwise group comparisons. Results. After excluding 6 rats that died unexpectedly, blood samples were obtained from 16, 14, and 20 rats in the control group, 70% hepatectomy group, and 90% hepatectomy group. There was a significant increase in area under the concentration-time curve from time zero to the time of the last measurable concentration between the 70% and 90% hepatectomy group (P<0.001). The volume of distribution at steady state was significantly decreased between the control and 70% hepatectomy group (P<0.001). The clearance was significantly different in all pairwise group comparisons (P<0.001). Conclusions. The vascular clearance of Gd-EOB-DTPA can identify the difference in liver function in a rat hepatectomy model.

scholarly journals Pharmacokinetic Profile of μSMIN Plus™, a new Micronized Diosmin Formulation, after Oral Administration in Rats

2015 ◽  
Vol 10 (9) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Rosario Russo ◽  
Angelo Mancinelli ◽  
Michele Ciccone ◽  
Fabio Terruzzi ◽  
Claudio Pisano ◽  
...  
Keyword(s):  
Oral Administration ◽  
Plasma Concentrations ◽  
Compartmental Analysis ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Sprague Dawley ◽  
Time Curve ◽  
Maximum Plasma Drug Concentration

Diosmin is a naturally occurring flavonoid present in citrus fruits and other plants belonging to the Rutaceae family. It is used for the treatment of chronic venous insufficiency (CVI) for its pheblotonic and vaso-active properties, safety and tolerability as well. The aim of the current in vivo study was to investigate the pharmacokinetic profile of a branded micronized diosmin (μSMIN Plus™) compared with plain micronized diosmin in male Sprague-Dawley rats. After oral administration by gastric gavage, blood samples were collected via jugular vein catheters at regular time intervals from baseline up to 24 hours. Plasma concentrations were assessed by LC/MS. For each animal, the following pharmacokinetic parameters were calculated using a non-compartmental analysis: maximum plasma drug concentration (Cmax), time to reach Cmax (Tmax), area under the plasma concentration-time curve (AUC0-last), elimination half-life (t1/2), and relative oral bioavailability (%F). The results of the current study clearly showed an improvement in the pharmacokinetic parameters in animals treated with μSMIN Plus™ compared with animals treated with micronized diosmin. In particular, μSMIN Plus™ showed a 4-fold increased bioavailability compared with micronized diosmin. In conclusion, the results from the current study provided a preliminary pharmacokinetic profile for μSMIN Plus™, which may represent a new tool for CVI management.

scholarly journals Paritaprevir and Ritonavir Liver Concentrations in Rats as Assessed by Different Liver Sampling Techniques

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Charles S. Venuto ◽  
Marianthi Markatou ◽  
Yvonne Woolwine-Cunningham ◽  
Rosemary Furlage ◽  
Andrew J. Ocque ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Needle Aspiration ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Time Curve ◽  
Tissue Samples ◽  
Drug Concentrations ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass

ABSTRACT The liver is crucial to pharmacology, yet substantial knowledge gaps exist in the understanding of its basic pharmacologic processes. An improved understanding for humans requires reliable and reproducible liver sampling methods. We compared liver concentrations of paritaprevir and ritonavir in rats by using samples collected by fine-needle aspiration (FNA), core needle biopsy (CNB), and surgical resection. Thirteen Sprague-Dawley rats were evaluated, nine of which received paritaprevir/ritonavir at 30/20 mg/kg of body weight by oral gavage daily for 4 or 5 days. Drug concentrations were measured using liquid chromatography-tandem mass spectrometry on samples collected via FNA (21G needle) with 1, 3, or 5 passes (FNA1, FNA3, and FNA5); via CNB (16G needle); and via surgical resection. Drug concentrations in plasma were also assessed. Analyses included noncompartmental pharmacokinetic analysis and use of Bland-Altman techniques. All liver tissue samples had higher paritaprevir and ritonavir concentrations than those in plasma. Resected samples, considered the benchmark measure, resulted in estimations of the highest values for the pharmacokinetic parameters of exposure (maximum concentration of drug in serum [C max] and area under the concentration-time curve from 0 to 24 h [AUC0–24]) for paritaprevir and ritonavir. Bland-Altman analyses showed that the best agreement occurred between tissue resection and CNB, with 15% bias, followed by FNA3 and FNA5, with 18% bias, and FNA1 and FNA3, with a 22% bias for paritaprevir. Paritaprevir and ritonavir are highly concentrated in rat liver. Further research is needed to validate FNA sampling for humans, with the possible derivation and application of correction factors for drug concentration measurements.

scholarly journals Pharmacokinetics and Efficacies of Liposomal and Conventional Formulations of Tobramycin after Intratracheal Administration in Rats with Pulmonary Burkholderia cepacia Infection

2002 ◽  
Vol 46 (12) ◽  
pp. 3776-3781 ◽  
Author(s):  
Jean-Francois Marier ◽  
Jean Lavigne ◽  
Murray P. Ducharme
Keyword(s):  
Burkholderia Cepacia ◽  
Compartment Model ◽  
Lung Infection ◽  
Liposomal Formulation ◽  
Resistant Bacteria ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Time Curve ◽  
Intratracheal Administration ◽  
Β Phase

ABSTRACT The objective of the present study was to determine the pharmacokinetics and efficacies of liposomal and conventional formulations of tobramycin against Burkholderia cepacia in a model of chronic lung infection. Male Sprague-Dawley rats were inoculated intratracheally with 106 CFU of a very resistant strain of B. cepacia (strain BC 1368; MIC, 128 μg/ml) to establish lung infection. A 1,200-μg dose of tobramycin was administered intratracheally as a liposomal formulation and as a conventional formulation. Rats were anesthetized and exsanguinated by cardiac puncture at different times over 24 h to assess pulmonary tobramycin concentrations and the number of residual CFU. Pharmacokinetic parameters were calculated by using a two-compartment model with NONMEM. The mean half-life at the β phase (t 1/2β) and the pulmonary exposure (the area under the concentration-time curve [AUC]) of liposomal tobramycin were 19.7 h (coefficient of variation [CV], 24.2%) and 6,811 μg · h/lungs (CV, 19.7%), respectively. The pharmacokinetics of conventional tobramycin were statistically different, with a t 1/2β and AUC of 12.9 h (CV, 31.4%) and 821 μg · h/lungs (CV, 15.0%), respectively. Pearson chi-square analyses were performed on residual CFU data distributed in the following categories: <103, 103 to 105, and >105. Differences in CFU data between formulations showed a statistical trend (P < 0.10) when data from all time points were used, and statistically significant differences were found after 12 h (P < 0.05), with greater eradication achieved with the liposomal formulation. In conclusion, intratracheal administration of tobramycin in liposomes was associated with marked changes in the pharmacokinetics of the drug in the lung and an apparent trend for a prolonged efficacy against B. cepacia. These results support the hypothesis that inhalation of liposomal tobramycin may improve the management of chronic pulmonary infections caused by resistant bacteria in patients with cystic fibrosis.

scholarly journals Effect of epigallocatechin gallate on aluminum chloride-induced changes in behavior, biochemical parameters, and spermatogenesis of Sprague-Dawley rats

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Subramani Parasuraman ◽  
Brenda Ngu Yen Qin ◽  
Lam Chew Hui ◽  
James Yu Kar Beng
Keyword(s):  
Vitamin C ◽  
Aluminum Chloride ◽  
Biochemical Parameters ◽  
Sperm Count ◽  
Epigallocatechin Gallate ◽  
Biochemical Changes ◽  
Male Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Induced Changes

Abstract Background Epigallocatechin gallate (EGCG) acts as an antioxidant by preventing oxidative stress. The effect of EGCG on aluminum-induced testicular injury is not clear. Hence, the present study is planned to investigate the effect of EGCG on aluminum chloride (AlCl3)-induced changes in behavior, biochemical parameters, and spermatogenesis in male Sprague-Dawley rats. The rats were divided into six groups with six animals each. All the animals were administered with respective assigned treatment once daily for 28 days. The animals in groups I to VI were administered with drug vehicle, AlCl3, vitamin C, EGCG, vitamin C, and EGCG, respectively. The animals in groups V and VI were additionally challenged with AlCl3 (10 mg/kg) immediately after vitamin C and EGCG administration, respectively. Changes in behavior were measured on day 1, 14 and 28. At the end of the study, the blood sample was collected from all the animals, and the serum was separated and used for biochemical analysis. Later, the rats were subjected to bilateral orchiectomy; sperm was collected from the cauda epididymis for microscopic examination. Then, the animals were sacrificed, and the organs such as the brain, lungs, heart, liver, kidney, spleen, and testis were collected for organ weight analysis. Results The animal administered with AlCl3 showed a reduction in locomotor activity, grip strength, and escape latency time whereas vitamin C prevented the effect of AlCl3. But, EGCG did not show any significant changes in AlCl3-induced behavioral and biochemical changes. At the end of the study, vitamin C prevented AlCl3-induced behavioral and biochemical changes. The group of animals administered with AlCl3 showed a reduction in the number of spermatozoa whereas AlCl3 + vitamin C and AlCl3 + EGCG did not show any significant changes in the number of spermatozoa when compared to the control group. Conclusion EGCG prevented AlCl3-induced reduction in epididymal sperm count of male rats and did not show any significant effect on AlCl3-induced changes in behavior and biochemical parameters, whereas vitamin C had an ameliorative effect on AlCl3-induced changes in behavior, biochemical parameter, and spermatogenesis. Graphical abstract

scholarly journals Pharmacokinetics Interaction between Imatinib and Genistein in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Zhe Wang ◽  
Li Wang ◽  
Meng-ming Xia ◽  
Wei Sun ◽  
Cheng-ke Huang ◽  
...  
Keyword(s):  
Single Dose ◽  
Multiple Dose ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
Group Control Group

The objective of this work was to investigate the effect of orally administered genistein on the pharmacokinetics of imatinib and N-desmethyl imatinib in rats. Twenty-five healthy male SD (Sprague-Dawley) rats were randomly divided into five groups: A group (control group), B group (multiple dose of 100 mg/kg genistein for consecutive 15 days), C group (multiple dose of 50 mg/kg genistein for consecutive 15 days), D group (a single dose of 100 mg/kg genistein), and E group (a single dose of 50 mg/kg genistein). A single dose of imatinib is administered orally 30 min after administration of genistein (100 mg/kg or 50 mg/kg). The pharmacokinetic parameters of imatinib and N-desmethyl imatinib were calculated by DAS 3.0 software. The multiple dose of 100 mg/kg or 50 mg/kg genistein significantly (P<0.05) decreased theAUC0-tandCmaxof imatinib.AUC0-tand theCmaxof N-desmethyl imatinib were also increased, but without any significant difference. However, the single dose of 100 mg/kg or 50 mg/kg genistein has no effect on the pharmacokinetics of imatinib and N-desmethyl imatinib. Those results indicated that multiple dose of genistein (100 mg/kg or 50 mg/kg) induces the metabolism of imatinib, while single dose of genistein has no effect.

scholarly journals Effect of the Phragmitis Rhizoma Aqueous Extract on the Pharmacokinetics of Docetaxel in Rats

2019 ◽  
Vol 22 (5) ◽  
pp. 326-332
Author(s):  
Sarah Shin ◽  
No Soo Kim ◽  
Young Ah Kim ◽  
Hea Ry Oh ◽  
Ok-Sun Bang
Keyword(s):  
Aqueous Extract ◽  
Statistical Significance ◽  
Ultra Performance Liquid Chromatography ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Mass Spectrometry System ◽  
Phragmitis Rhizoma

Background: Traditionally, Phragmitis rhizoma has been prescribed to relive a fever, vomiting, dysuria, and constipation, and to promote secretion of fluids. In addition, recent studies have reported its efficacy as a diuretic and antiemetic. Our previous study demonstrated that the Phragmitis rhizoma aqueous extract (EPR) ameliorates docetaxel (DTX)-induced myelotoxicity. Aim and Objective: This study was aimed to investigate the effects of EPR on the pharmacokinetics of DTX in Sprague–Dawley rats. Materials & Methods: The animals received an intravenous injection of DTX (5 mg/kg) with or without oral EPR (100 mg/kg) pretreatment for 1 or 6 days. The pharmacokinetics of plasma DTX was analyzed using an ultra-performance liquid chromatography-tandem mass spectrometry system, and pharmacokinetic parameters were estimated via noncompartmental analysis. Results: Relative to the control group (DTX alone), EPR pretreatment did not affect significantly the overall profiles of plasma DTX levels. Consecutively pretreated EPR for 6 days slightly altered AUC0-t and Cmax of DTX by 122 and 145.9%, respectively, but these data did not reach the threshold of statistical significance (p > 0.05). Conclusion: These results indicate that DTX exposure may not be affected by EPR treatment at the dose level used in this study, suggesting that oral EPR can be used safely when taken with intravenously injected DTX. However, further studies under the stringent conditions are needed when chronic treatment of EPR and anticancer drug.

Effect Of 30-Day Administration Of Cellgevity® Supplement On Selected Rat Liver Cytochrome P450 Enzyme Activity And Supplement Interaction With Carbamazepine

2019 ◽  
Author(s):  
Seth Kwabena Amponsah ◽  
Benoit Banga Nguessan ◽  
Martin Akandawen ◽  
Abigail Aning ◽  
Sedem Yawa Agboli ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Cytochrome P450 ◽  
Rat Liver ◽  
Normal Saline ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Cytochrome P450 Enzyme ◽  
Sprague Dawley ◽  
Liver Cytochrome ◽  
Sd Rats

Abstract BackgroundThere is considerable evidence that many patients concurrently take dietary supplements with conventional drugs, with a risk of potential drug-supplement interaction. The aim of this study was to determine the effect of Cellgevity® supplement on selected rat liver cytochrome P450 (CYP) enzymes and on the pharmacokinetics of carbamazepine.MethodsSprague-Dawley (SD) rats were put into 5 groups and modulation of CYP enzyme activity by Cellgevity® was determined by comparing the enzyme activity of Cellgevity-treated groups with the negative control group after 30 days of treatment. For the effect of Cellgevity® on the pharmacokinetics of carbamazepine, 12 SD rats were put into 2 groups; one group received an oral administration of carbamazepine plus Cellgevity®, and the other carbamazepine plus normal saline. Blood samples were collected at specific time points and analyzed for levels of carbamazepine. ResultsActivities of CYP1A1/2, CYP2C9 and CYP2D6 were significantly increased by Cellgevity®. The pharmacokinetic parameters for rats administered carbamazepine with Cellgevity® vis-a-vis carbamazepine with normal saline were changed as follows: Cmax; 20 μmol/L vs 11 μmol/L, AUC0→24; 347 μmol.h/L vs 170 μmol.h/L, Ke; 0.28 h-1 vs 0.41 h-1, and t1/2; 2.3 h vs 1.7 h, respectively.ConclusionsCellgevity® increased the activity of rat CYP1A1/2, CYP2C9 and CYP2D6, and also altered the pharmacokinetics of carbamazepine in rats.

scholarly journals EFFECT OF 70% ETHANOL EXTRACT OF ORTHOSIPHONIS STAMINEUS BENTH LEAVES ON THE PHARMACOKINETIC PARAMETERS OF FUROSEMIDE IN MALE WHITE RATS

2017 ◽  
Vol 9 ◽  
pp. 54
Author(s):  
Riana Maya Oktaviani ◽  
Santi Purna Sari ◽  
Yahdiana Harahap
Keyword(s):  
White Male ◽  
Area Under The Curve ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Male Rats ◽  
Combination Group ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Sprague Dawley ◽  
White Rats

Objective: This study aimed to observe the effect of the 70% ethanol extract of Orthosiphonis stamineus Benth leaves on the pharmacokineticparameters of furosemide in white male rats.Methods: 18 Sprague–Dawley male rats were divided into three groups: The normal control group was given only 1% carboxymethyl cellulose,the furosemide group was given 7.2 mg/200 g body weight (BW) suspension of furosemide, and the combination group was given 700 mg/kg BWsuspension of the 70% ethanolic extract of O. stamineus Benth leaves for 4 days followed by a 7.2 mg/200 g BW suspension of furosemide. On the4th day of treatment, we performed orbital sinus blood sampling on the eyes of the rats and analyzed the levels of furosemide in plasma using highperformanceliquid chromatography.Results: Therefore, the results showed that the administration of the 70% ethanol extract of O. stamineus Benth leaves improves the pharmacokineticparameters of furosemide on Cpmax and the area under the curve (p<0.05).Conclusion: This study concludes that the 70% ethanol extract of O. stamineus Benth leaves improves the pharmacokinetic parameters of furosemidein white male rats.

scholarly journals The Herb-Drug Pharmacokinetic Interaction of Fluoxetine and Its Metabolite Norfluoxetine with a Traditional Chinese Medicine in Rats by LC-MS/MS

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Lijing Yan ◽  
Sheng Wang ◽  
Linlin Zhao ◽  
Juan Qiu ◽  
Lu Zhou ◽  
...  
Keyword(s):  
Multiple Dose ◽  
Dose Group ◽  
Pharmacokinetic Interaction ◽  
Primary Objective ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Time Curve ◽  
Liquid Chromatography Tandem Mass ◽  
Healthy Adult Male ◽  
Group B

Background. Fluoxetine (FLU) is the first-line and widely used medication for depression. The combination of Chaihu Shugan san (CSGS) and FLU is commonly used to enhance antidepressant effects and reduce side effects. Objective. The primary objective of this study was to investigate the potential pharmacokinetic effect of CSGS on FLU. Materials and Methods. Thirty-two healthy adult male Sprague-Dawley (SD) rats were randomly divided into four groups, the fluoxetine group and multiple dose groups A, B, and C. The rats in the different groups were orally administered with a combination of FLU and different doses of CSGS for 14 d. On the fifteenth day, serial blood samples were taken from the caudal vein before the administration and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24, 36, and 48 h after the administration. A liquid-liquid extraction method was applied to extract the analytes from serum. Then, the concentrations of FLU and its metabolite, norfluoxetine (NOF), were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated by DAS 3.2.8 program and compared by statistic analysis. Results. Compared with the FLU group, the FLU and NOF area under the plasma concentration-time curve (AUC) (0–∞) in multiple dose group C was significantly increased, while the NOF AUCs (0–∞) in multiple dose group A and multiple dose group B were decreased. Compared with the FLU group, the NOF clearance (CL) in multiple dose group C was decreased, while the CL in multiple dose groups A and B was increased. Discussion and Conclusion. There were some differences in pharmacokinetic parameters between the FLU group and multiple dose groups, and CSGS can affect the pharmacokinetics of fluoxetine.

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