• Title/Summary/Keyword: p-gp

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Effects of Fluvastatin on the Pharmacokinetics of Repaglinide: Possible Role of CYP3A4 and P-glycoprotein Inhibition by Fluvastatin

  • Lee, Chong-Ki;Choi, Jun-Shik;Bang, Joon Seok
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.3
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    • pp.245-251
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    • 2013
  • The purpose of this study was to investigate the effects of fluvastatin on the pharmacokinetics of repaglinide in rats. The effect of fluvastatin on P-glycoprotein and CYP3A4 activity was evaluated. The pharmacokinetic parameters and blood glucose concentrations were also determined after oral and intravenous administration of repaglinide to rats in the presence and absence of fluvastatin. Fluvastatin inhibited CYP3A4 activity in a concentration-dependent manner with a 50% inhibition concentration($IC_{50}$) of 4.1 ${\mu}M$ and P-gp activity. Compared to the oral control group, fluvastatin significantly increased the AUC and the peak plasma level of repaglinide by 45.9% and 22.7%, respectively. Fluvastatin significantly decreased the total body clearance (TBC) of repaglinide compared to the control. Fluvastatin also significantly increased the absolute bioavailability (BA) of repaglinide by 46.1% compared to the control group. Moreover, the relative BA of repaglinide was 1.14- to 1.46-fold greater than that of the control. Compared to the i.v. control, fluvastatin significantly increased the $AUC_{0-{\infty}}$ of i.v. administered repaglinide. The blood glucose concentrations showed significant differences compared to the oral controls. Fluvastatin enhanced the oral BA of repaglinide, which may be mainly attributable to the inhibition of the CYP3A4-mediated metabolism of repaglinide in the small intestine and/or liver, to the inhibition of the P-gp efflux transporter in the small intestine and/or to the reduction of TBC of repaglinide by fluvastatin. The study has raised the awareness of potential interactions during concomitant use of repaglinide with fluvastatin. Therefore, the concurrent use of repaglinide and fluvastatin may require close monitoring for potential drug interactions.

Pharmacokinetic Interaction Between Atorvastatin and Nifedipine (아톨바스타틴과 니페디핀의 약물동태학적 상호작용)

  • Moon, Hong-Seop;Choi, Jun-Shik
    • Korean Journal of Clinical Pharmacy
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    • v.20 no.1
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    • pp.25-29
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    • 2010
  • The purpose of this study was to investigate the effect of atorvastatin on the pharmacokinetics of nifedipine (6 mg/kg) after oral administration of nifedipine with or without atorvastatin (0.5 and 2.0 mg/kg) in rats, and also was to evaluate to the effect of atorvastatin on the CYP3A4 activity. The 50% inhibiting concentration ($IC_{50}$) values of atorvastatin on CYP3A4 activity is 46.1 ${\mu}M$. Atorvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner. Coadministration of atorvastatin increased significantly (p<0.05, 2.0 mg/kg) the plasma concentration-time curve (AUC) and the peak concentration ($C_{max}$) of nifedipine compared to the control group. The relative bioavailability (RB%) of nifedipine was increased from 1.15- to 1.37-fold. Coadministration of atorvastatin did not significantly change the terminal half-life ($T_{1/2}$) and the time to reach the peak concentration ($T_{max}$) of nifedipine. Based on these results, we can make a conclusion that the significant changes of these pharmacokinetic parameters might be due to atorvastatin, which possesses the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein (P-gp) efflux pump in the intestinal mucosa. It might be suggested that atorvastatin altered disposition of nifedipine by inhibition of both the first-pass metabolism and P-glycoprotein efflux pump in the small intestine of rats. In conclusion, the presence of atorvastatin significantly enhanced the oral bioavailability of nifedipine, suggesting that concurrent use of atorvastatin with nifedipine should require close monitoring for potential drug interation.

A study on vegetation and soil environmental characteristics of green roof in Daejeon Metropolitan City (대전광역시 옥상녹화 지역의 식생현황 및 토양환경 특성에 관한 연구)

  • Lee, Sang-Jin;Park, Gwan-Soo;Lee, Dong-Kun;Jang, Seong-Wan;Park, Beom-Hwan;Lee, Hang-Goo;Yun, Joon-Young;Jang, Kwan-Woo;Lee, Seung-Woo;Lee, Ho-Young;Kwon, Oh-Jung;Lee, Sook-Mee;Kil, Sung-Ho
    • Korean Journal of Agricultural Science
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    • v.38 no.4
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    • pp.641-649
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    • 2011
  • This study was to analyze the soil environmental characteristics and vegetation status of green roof in Daejeon Metropolitan City. The investigated floras of vascular plants are 17 families, 26 genera, 28 species in Seo-Gu Daejeon District Office Building (SG), 25 families, 49 genera, 56 species in Galma Public Library (GP), and 34 families, 57 genera, 60 species in Daejeon City Hall (DC) respectively. Although the larger area shows the more numbers of species in introduced plants and naturalized plant, the naturalized plant ratios were similar with each other. They were 10.71%, 10.71%, and 11.67% at SG, GP, and DC respectively. As a result of analysis on soil physical property, soil depths including vegetation soil and drainage soil of 3 green roofs were 30cm. The depths of vegetation soil at SG, GP, and DC were 0~8cm, 0~10cm, 0~10cm respectively. As a results of soil chemical properties of our study, soil pH of vegetation soil and drainage soil were a range of 6.42 and 7.43, and a range of 6.55 and 7.43 on the average respectively. Available-P contents of vegetation soil and drainage soil were a range of 153.33 and 366.33mg/kg, and a range of 136.67 and 242.67 mg/kg which is very high, respectively. Carbon contents in soil at vegetation soil and drainage soil were a range of 3.16 and 6.38%, and a range of 1.63 and 2.47% respectively. Carbon storage per square meter within 30 cm were 2.76 kg, 2.99 kg, and 3.66 kg at SG, GP, and DC respectively.

Quantification of the tug-back by measuring the pulling force and micro computed tomographic evaluation

  • Jeon, Su-Jin;Moon, Young-Mi;Seo, Min-Seock
    • Restorative Dentistry and Endodontics
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    • v.42 no.4
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    • pp.273-281
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    • 2017
  • Objectives: The aims of this study were to quantify tug-back by measuring the pulling force and investigate the correlation of clinical tug-back pulling force with in vitro gutta-percha (GP) cone adaptation score using micro-computed tomography (${\mu}CT$). Materials and Methods: Twenty-eight roots from human single-rooted teeth were divided into 2 groups. In the ProTaper Next (PTN) group, root canals were prepared with PTN, and in the ProFile (PF) group, root canals were prepared using PF (n = 14). The degree of tug-back was scored after selecting taper-matched GP cones. A novel method using a spring balance was designed to quantify the tug-back by measuring the pulling force. The correlation between tug-back scores, pulling force, and percentage of the gutta-percha occupied area (pGPOA) within apical 3 mm was investigated using ${\mu}CT$. The data were analyzed using Pearson's correlation analysis, one-way analysis of variance (ANOVA) and Tukey's test. Results: Specimens with a strong tug-back had a mean pulling force of 1.24 N (range, 0.15-1.70 N). This study showed a positive correlation between tug-back score, pulling force, and pGPOA. However, there was no significant difference in these factors between the PTN and PF groups. Regardless of the groups, pGPOA and pulling force were significantly higher in the specimens with a higher tug-back score (p < 0.05). Conclusions: The degree of subjective tug-back was a definitive determinant for master cone adaptation in the root canal. The use of the tug-back scoring system and pulling force allows the interpretation of subjective tug-back in a more objective and quantitative manner.

Evaluation Scheme of the GPS Positional Accuracy for Dynamic Bus Route Information using SMB(Single Buffering Method) (단일 버퍼링 기법을 이용한 동적 버스 노선 정보의 GPS 위치 정확도 평가 방안)

  • Park, Hong-Gi;Joo, Yong-Jin
    • Journal of the Korean Society of Surveying, Geodesy, Photogrammetry and Cartography
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    • v.29 no.6
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    • pp.677-685
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    • 2011
  • In order to enhance public transportation and to maintain information credibility, improvement of accuracy regarding route and positional information of public transport is very significant. There have been a variety of methods using GPS to measure accuracy of location-based services. However, the researches of evaluation regarding kinematic position of linear objects measured by vehicle/kinematic GPS are still insufficient. That's why our paper aims to suggest method of evaluation accuracy on a real-time bus route surveyed by GPS by SBM(Single Buffering Method). To make it come true, we compared the findings on the static and dynamic positioning by using PP(Point Positioning), DGPS and GPS/INS integrated systems and analyzed the accuracy and error effects among them, focusing on Anyang city. Consequently, we can find out that in case of P.P. comparing positioning accuracy between RTK DGPS and GPS/INS, both of them have survey result within a margin of error of 5m. More importantly, we can evaluate positional accuracy of each GPS system based on the work provision of a public survey such as error for P.P.(14.5m, 18.1m), DGPS(16.9m, 18.5m), and GPS/INS(18.4m, 18.5m). We are expecting that proposed method in our paper can be utilized in a wide range of categories such as feasibility testing of GPS field survey and high accuracy of positioning for Bus Information System.

Evaluating fermentation quality, in vitro digestibility and aerobic stability of a total mixed ration ensiled with different additives on Tibet plateau

  • Dong, Zhihao;Wang, Siran;Zhao, Jie;Li, Junfeng;Liu, Qinhua;Bao, Yuhong;Shao, Tao
    • Animal Bioscience
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    • v.34 no.2
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    • pp.223-232
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    • 2021
  • Objective: To investigate the improvement in utilization efficiency of total mixed ration (TMR) on Tibetan plateau, TMR were ensiled with different additives. Methods: A total of 150 experimental silos were prepared in a completely randomized design to evaluate the six treatments: i) control (without additive), ii) Lactobacillus buchneri (L. buchneri), iii) acetic acid, iv) propionic acid, v) 1,2-propanediol; and vi) 1-propanol. After 90 days of ensiling, silos were opened for fermentation quality and in vitro analysis, and then subjected to an aerobic stability test for 14 days. Results: Treating with L. buchneri, acetic acid, 1,2-propanediol and 1-propanol decreased propionic acid contents and yeast number, whereas increased (p<0.05) pH, acetic acid and ethanol contents in the fermented TMR. Despite increased dry matter (DM) loss in the TMRs treated with 1,2-propanediol and 1-pronanol, additives did not affect (p>0.05) all in vitro parameters including gas production at 24 h (GP24), GP rate constant, potential GP, in vitro DM digestibility and in vitro neutral detergent fibre digestibility. All additives improved the aerobic stability of ensiled TMR to different extents. Specially, aerobic stability of the ensiled TMR were substantially improved by L. buchneri, acetic acid, 1,2-propanediol, and 1-propanol, indicated by stable pH and lactic acid content during the aerobic stability test. Conclusion: L. buchneri, acetic acid, 1,2-propanediol, and 1-propanol had no adverse effect on in vitro digestibility, while ensiling TMR with the additives produced more acetic acid and ethanol, subsequently resulting in improvement of aerobic stability. There is a potential for some fermentation boosting additives to enhance aerobic stability of fermented TMR on Tibetan plateau.

Detection of Antibodies to Classical Swine Fever Virus gp55 in Muscle Fluid (Classical Swine Fever Virus gp55 항원에 대한 Muscle Fluid 항체 측정)

  • Jung, Jae-yun;Jung, Byeong-yeal;Kim, Bong-hwan
    • Korean Journal of Veterinary Research
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    • v.43 no.2
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    • pp.263-270
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    • 2003
  • The objective of the present study was to investigate the use of fluid released from muscle samples as an alternative to serum for ELISA to detect classical swine fever(CSF) virus antibodies in slaughter pigs. The optimal correspondence between serum 1:20 OD values and muscle fluid OD values was achieved at a muscle fluid dilution of 1:2. Significant correlation was found between serum and neck muscle ELISA ($r_s=0.880$, p<0.0001, ${\kappa}=0.82$; specificity of 97.0% and sensitivity 90.6%). The semimembranous muscle showed similar correlation in CSF ELISA($r_s=0.877$, p<0.0001, ${\kappa}=0.75$; specificity of 94.1% and sensitivity 89.1%). High correlation was obtained between serum and mesenteric lymph node in the CSF ELISA ($r_s=0.937$, p<0.0001, ${\kappa}=0.87$; specificity of 97.1% and sensitivity 93.0%). Measmement agreement between serum ELISA and muscle fluid ELISA was calculated and expressed as limits of agreement. The correspondence of ELISA of serum and muscle fluid indicated limits of agreement. Above 95% of all muscle fluid values were distributed within this limits of agreement. Among the samples used for ELISA for detecting CSFV antibodies, mesenteric lymph node had the most correlation and agreement with serum ELISA. F-test for comparison of variances showed no significant difference between the serum and muscle fluid. In conclusion, muscle fluid is a useful postmortem alternative to serum to detect CSFV antibodies.

A Novel Phage Display Vector for Easy Monitoring of Expressed Proteins

  • Shin, Young-Chul;Kim, Young-Eun;Cho, Tae-Ju
    • BMB Reports
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    • v.33 no.3
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    • pp.242-248
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    • 2000
  • Phage display of proteins is a powerful tool for protein engineering since a vast library of sequences can be rapidly screened for a specific property. In this study, we develop da new phage display vector that was derived from a pET-25b(+) vector. The pET-25b(+) was modified in order that the expressed protein would have a T7-tag at the amino terminus and GpS (a major coat protein of M13 phage) at the carboxyl terminus. Another vector without the gp8 gene was also constructed. The newly developed phagemid vectors have several advantageous features. First, it is easy to examine whether or not the target proteins are functional and faithfully transported into the periplasmic space. This feature is due to the fact that recombinant proteins are produced abundantly in the pET system. Second, the T7-tag makes it possible to detect any target proteins that are displayed on the surface of filamentous bacteriophage. To verify the utility of the vector, the clones containing the glutathione S-transferase (GST) gene as a target were examined. The result showed that the GST produced from the recombinant vector was successfully transported into the periplasmic space and had the anticipated enzyme activity. Western blot analysis using a T7-tag antibody also showed the presence of the target protein displayed on the surface of the phage. The phages prepared from the recombinant clones were able to bind to glutathione-Sepharose and then eluted with glutathione. These results showed that the new vectors developed in this study are useful for the phage display of proteins.

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Defining the N-Linked Glycosylation Site of Hantaan Virus Envelope Glycoproteins Essential for Cell Fusion

  • Zheng, Feng;Ma, Lixian;Shao, Lihua;Wang, Gang;Chen, Fengzhe;Zhang, Ying;Yang, Song
    • Journal of Microbiology
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    • v.45 no.1
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    • pp.41-47
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    • 2007
  • The Hantaan virus (HTNV) is an enveloped virus that is capable of inducing low pH-dependent cell fusion. We molecularly cloned the viral glycoprotein (GP) and nucleocapsid (NP) cDNA of HTNV and expressed them in Vero E6 cells under the control of a CMV promoter. The viral gene expression was assessed using an indirect immunofluorescence assay and immunoprecipitation. The transfected Vero E6 cells expressing GPs, but not those expressing NP, fused and formed a syncytium following exposure to a low pH. Monoclonal antibodies (MAbs) against envelope GPs inhibited cell fusion, whereas MAbs against NP did not. We also investigated the N-linked glycosylation of HTNV GPs and its role in cell fusion. The envelope GPs of HTNV are modified by N-linked glycosylation at five sites: four sites on G1 (N134, N235, N347, and N399) and one site on G2 (N928). Site-directed mutagenesis was used to construct eight GP gene mutants, including five single N-glycosylation site mutants and three double-site mutants, which were then expressed in Vero E6 cells. The oligosaccharide chain on residue N928 of G2 was found to be crucial for cell fusion after exposure to a low pH. These results suggest that G2 is likely to be the fusion protein of HTNV.

Purification, Bacteriolytic Action and Plasmid Isolation of Acidocin 4A Produced by Lactobacillus acidophilus GP4A (Lactobacillus acidophilus GP4A 박테리오신의 정제, Bacteriolytic 작용 및 생산 관련 Plasmid의 선별)

  • Han, Gyeong-Sik;Jeon, U-Min;Kim, Yeong-Hun;Kim, Se-Heon
    • Journal of Dairy Science and Biotechnology
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    • v.21 no.2
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    • pp.114-119
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    • 2003
  • Acidocin 4A produced by Lactobacillus acidophilus GP4A was purified to homogeneity by ammonium sulfate precipitation and sequential chromatographies containing Octyl sepharose CL-4B column, $C_{18}$ Sep-Pak Cartridge, $C_{18}$ RP HPLC and HPLC gel filtration. Tricine SDS-PACE resulted in a single band with estimated molecular mass of 4.1 kDa corresponding to the polypeptide weight marker. Electron microscopy of acidocin-treated indicator cells(L. delbrueckii subsp. lactis ATCC 4797) confirmed that acidocin 4A presented bacteriolytic effect, resulting in cell lysis. Curing trial using ethidium bromide (EtBr) was carried out to examine whether acidocin 4A determinant was encoded either by chromosome or on plasmid. The plasmid designated as pLA4A, being about 20 kb in size, was responsible for acidocin 4A production and immunity to host cells.

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