LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 11

Search options

  1. Article ; Online: Selective Suppression of CYP3A4 mRNA and Enzyme Activity by Epidermal Growth Factor in Plated Human Hepatocytes.

    Zhang, J George / Wang, Duan / Ho, Thuy / Clark, Robert J / Stresser, David M

    Drug metabolism letters

    2017  Volume 11, Issue 2, Page(s) 119–127

    Abstract: Background: Epidermal Growth Factor (EGF) is a well-known mitogen that has importance in cell proliferation and differentiation. This property has led to the common use of EGF as an additive to some cell culture media. EGF has been previously shown to ... ...

    Abstract Background: Epidermal Growth Factor (EGF) is a well-known mitogen that has importance in cell proliferation and differentiation. This property has led to the common use of EGF as an additive to some cell culture media. EGF has been previously shown to modulate constitutive Cytochrome P450 (CYP) expression in vitro.
    Objectives: To assess the influence of EGF on the basal and induced expression of CYP3A4, CYP1A2 and CYP2B6 in plated human hepatocytes.
    Methods: Human hepatocytes were treated with EGF with and without in the presence of positive control inducers. After treatment, CYP isoform mRNA expression and enzyme activity were measured.
    Results: EGF at concentrations ranging from 0.001-500 ng/mL resulted in a concentration-dependent decrease in basal CYP3A4 catalytic activity by up to 92%. In contrast, rifampicin (RIF)-induced activity was decreased only slightly (up to 23%). CYP3A4 mRNA also decreased in an EGF concentrationdependent manner. In contrast to CYP3A4, CYP1A2 and CYP2B6 activity and mRNA were either not suppressed or suppressed to a lower extent. The preferential effect with CYP3A4 was confirmed in 4 additional donors using a single concentration of EGF (10 ng/mL) and time-dependence experiments revealed that suppression appeared after only 24h of treatment.
    Conclusion: Because of the larger effect on the basal CYP3A4 compared to the induced response, EGF as a media additive enables a higher dynamic range in a CYP3A4 induction assay, potentially expanding the range of donor hepatocytes suitable for use in induction studies. These findings also suggest that EGF may be an important regulator of CYP3A4 expression in vivo.
    MeSH term(s) Cell Culture Techniques/methods ; Cells, Cultured ; Culture Media/metabolism ; Cytochrome P-450 CYP1A2/metabolism ; Cytochrome P-450 CYP2B6/metabolism ; Cytochrome P-450 CYP3A/genetics ; Cytochrome P-450 CYP3A/metabolism ; Cytochrome P-450 CYP3A Inducers/pharmacology ; Cytochrome P-450 CYP3A Inhibitors/metabolism ; Drug Discovery/methods ; Epidermal Growth Factor/metabolism ; Hepatocytes/enzymology ; Humans ; RNA, Messenger/metabolism ; Rifampin/pharmacology
    Chemical Substances Culture Media ; Cytochrome P-450 CYP3A Inducers ; Cytochrome P-450 CYP3A Inhibitors ; RNA, Messenger ; Epidermal Growth Factor (62229-50-9) ; CYP1A2 protein, human (EC 1.14.14.1) ; CYP2B6 protein, human (EC 1.14.14.1) ; Cytochrome P-450 CYP1A2 (EC 1.14.14.1) ; Cytochrome P-450 CYP2B6 (EC 1.14.14.1) ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; CYP3A4 protein, human (EC 1.14.14.55) ; Rifampin (VJT6J7R4TR)
    Language English
    Publishing date 2017-11-29
    Publishing country United Arab Emirates
    Document type Journal Article
    ISSN 1874-0758
    ISSN (online) 1874-0758
    DOI 10.2174/1872312811666171128141105
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Characterization of iron binding in IscA, an ancient iron-sulphur cluster assembly protein.

    Ding, Huangen / Clark, Robert J

    The Biochemical journal

    2004  Volume 379, Issue Pt 2, Page(s) 433–440

    Abstract: Iron-sulphur clusters are one of the most common types of redox centre in biology. At least six proteins (IscS, IscU, IscA, HscB, HscA and ferredoxin) have been identified as being essential for the biogenesis of iron-sulphur proteins in bacteria. It has ...

    Abstract Iron-sulphur clusters are one of the most common types of redox centre in biology. At least six proteins (IscS, IscU, IscA, HscB, HscA and ferredoxin) have been identified as being essential for the biogenesis of iron-sulphur proteins in bacteria. It has been shown that IscS is a cysteine desulphurase that provides sulphur for iron-sulphur clusters, and that IscU is a scaffold for the IscS-mediated assembly of iron-sulphur clusters. The iron donor for iron-sulphur clusters, however, remains elusive. Here we show that IscA is an iron binding protein with an apparent iron association constant of 3.0x10(19) M(-1), and that iron-loaded IscA can provide iron for the assembly of transient iron-sulphur clusters in IscU in the presence of IscS and L-cysteine in vitro. The results suggest that IscA is capable of recruiting intracellular iron and delivering iron for iron-sulphur clusters in proteins.
    MeSH term(s) Amino Acid Sequence ; Carrier Proteins/chemistry ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Electron Spin Resonance Spectroscopy ; Escherichia coli Proteins/chemistry ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Iron/analysis ; Iron/metabolism ; Iron-Sulfur Proteins/chemistry ; Iron-Sulfur Proteins/genetics ; Iron-Sulfur Proteins/metabolism ; Kinetics ; Molecular Sequence Data ; Sequence Homology, Amino Acid
    Chemical Substances Carrier Proteins ; Escherichia coli Proteins ; Iron-Sulfur Proteins ; IscA protein, E coli ; IscU protein, E coli ; Iron (E1UOL152H7)
    Language English
    Publishing date 2004-04-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2969-5
    ISSN 1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
    ISSN (online) 1470-8728
    ISSN 0006-2936 ; 0306-3275 ; 0264-6021
    DOI 10.1042/BJ20031702
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.110: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article: Limitations of quantum simulation examined by simulating a pairing Hamiltonian using nuclear magnetic resonance.

    Brown, Kenneth R / Clark, Robert J / Chuang, Isaac L

    Physical review letters

    2006  Volume 97, Issue 5, Page(s) 50504

    Abstract: Quantum simulation uses a well-known quantum system to predict the behavior of another quantum system. Certain limitations in this technique arise, however, when applied to specific problems, as we demonstrate with a theoretical and experimental study of ...

    Abstract Quantum simulation uses a well-known quantum system to predict the behavior of another quantum system. Certain limitations in this technique arise, however, when applied to specific problems, as we demonstrate with a theoretical and experimental study of an algorithm proposed by Wu, Byrd, and Lidar [Phys. Rev. Lett. 89, 057904 (2002).10.1103/PhysRevLett.89.057904] to find the low-lying spectrum of a pairing Hamiltonian. While the number of elementary quantum gates required scales polynomially with the size of the system, it increases inversely to the desired error bound E. Making such simulations robust to decoherence using fault tolerance requires an additional factor of approximately 1/E gates. These constraints, along with the effects of control errors, are illustrated using a three qubit NMR system.
    Language English
    Publishing date 2006-08-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208853-8
    ISSN 1079-7114 ; 0031-9007
    ISSN (online) 1079-7114
    ISSN 0031-9007
    DOI 10.1103/PhysRevLett.97.050504
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Z 4' 58/153: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article: From prostate to bone: key players in prostate cancer bone metastasis.

    Thobe, Megan N / Clark, Robert J / Bainer, Russell O / Prasad, Sandip M / Rinker-Schaeffer, Carrie W

    Cancers

    2011  Volume 3, Issue 1, Page(s) 478–493

    Abstract: Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our ... ...

    Abstract Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies.
    Language English
    Publishing date 2011-04-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers3010478
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article: IscA mediates iron delivery for assembly of iron-sulfur clusters in IscU under the limited accessible free iron conditions.

    Ding, Huangen / Clark, Robert J / Ding, Baojin

    The Journal of biological chemistry

    2004  Volume 279, Issue 36, Page(s) 37499–37504

    Abstract: Increasing evidence suggests that IscS, a cysteine desulfurase, provides sulfur for assembly of transient iron-sulfur clusters in IscU. IscU appears to act as a scaffold and eventually transfers the assembled clusters to target proteins. However, the ... ...

    Abstract Increasing evidence suggests that IscS, a cysteine desulfurase, provides sulfur for assembly of transient iron-sulfur clusters in IscU. IscU appears to act as a scaffold and eventually transfers the assembled clusters to target proteins. However, the iron donor for the iron-sulfur cluster assembly largely remains elusive. Here we find that Escherichia coli IscU fails to assemble iron-sulfur clusters when the accessible "free" iron in solution is limited by an iron chelator sodium citrate. Remarkably, IscA, an iron-sulfur cluster assembly protein with an iron association constant of 3.0 x 10(19) m(-1), is able to overcome the iron limitation due to sodium citrate and deliver iron for the IscS-mediated iron-sulfur cluster assembly in IscU. Substitution of the invariant cysteine residues Cys-99 or Cys-101 in IscA with serine completely abolishes the iron binding activity of the protein. The IscA mutants that fail to bind iron are unable to mediate iron delivery for the iron-sulfur cluster assembly in IscU under the limited accessible "free" iron conditions. The results suggest that IscA is capable of recruiting intracellular iron and providing iron for the iron-sulfur cluster assembly in IscU in cells in which the accessible "free" iron content is probably restricted.
    MeSH term(s) Carrier Proteins/genetics ; Carrier Proteins/physiology ; Citrates/pharmacology ; Escherichia coli/metabolism ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/physiology ; Iron/metabolism ; Iron-Sulfur Proteins/metabolism ; Mutagenesis, Site-Directed ; Sodium Citrate
    Chemical Substances Carrier Proteins ; Citrates ; Escherichia coli Proteins ; Iron-Sulfur Proteins ; IscA protein, E coli ; Sodium Citrate (1Q73Q2JULR) ; Iron (E1UOL152H7)
    Language English
    Publishing date 2004-07-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M404533200
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.108: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Book ; Online: A Two-Dimensional Lattice Ion Trap for Quantum Simulation

    Clark, Robert J. / Lin, Tongyan / Brown, Kenneth R. / Chuang, Isaac L.

    2008  

    Abstract: Quantum simulations of spin systems could enable the solution of problems which otherwise require infeasible classical resources. Such a simulation may be implemented using a well-controlled system of effective spins, such as a two-dimensional lattice of ...

    Abstract Quantum simulations of spin systems could enable the solution of problems which otherwise require infeasible classical resources. Such a simulation may be implemented using a well-controlled system of effective spins, such as a two-dimensional lattice of locally interacting ions. We propose here a layered planar rf trap design that can be used to create arbitrary two-dimensional lattices of ions. The design also leads naturally to ease of microfabrication. As a first experimental demonstration, we confine strontium-88 ions in a mm-scale lattice trap and verify numerical models of the trap by measuring the motional frequencies. We also confine 440 nm diameter charged microspheres and observe ion-ion repulsion between ions in neighboring lattice sites. Our design, when scaled to smaller ion-ion distances, is appropriate for quantum simulation schemes, e.g. that of Porras and Cirac (PRL 92 207901 (2004)). We note, however, that in practical realizations of the trap, an increase in the secular frequency with decreasing ion spacing may make a coupling rate that is large relative to the decoherence rate in such a trap difficult to achieve.

    Comment: 8 pages, 11 pdf figures, submitted to J. Appl. Phys
    Keywords Quantum Physics
    Subject code 612
    Publishing date 2008-09-16
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  7. Article ; Online: Evaluation of calibration curve-based approaches to predict clinical inducers and noninducers of CYP3A4 with plated human hepatocytes.

    Zhang, J George / Ho, Thuy / Callendrello, Alanna L / Clark, Robert J / Santone, Elizabeth A / Kinsman, Sarah / Xiao, Deqing / Fox, Lisa G / Einolf, Heidi J / Stresser, David M

    Drug metabolism and disposition: the biological fate of chemicals

    2014  Volume 42, Issue 9, Page(s) 1379–1391

    Abstract: Cytochrome P450 (P450) induction is often considered a liability in drug development. Using calibration curve-based approaches, we assessed the induction parameters R3 (a term indicating the amount of P450 induction in the liver, expressed as a ratio ... ...

    Abstract Cytochrome P450 (P450) induction is often considered a liability in drug development. Using calibration curve-based approaches, we assessed the induction parameters R3 (a term indicating the amount of P450 induction in the liver, expressed as a ratio between 0 and 1), relative induction score, Cmax/EC50, and area under the curve (AUC)/F2 (the concentration causing 2-fold increase from baseline of the dose-response curve), derived from concentration-response curves of CYP3A4 mRNA and enzyme activity data in vitro, as predictors of CYP3A4 induction potential in vivo. Plated cryopreserved human hepatocytes from three donors were treated with 20 test compounds, including several clinical inducers and noninducers of CYP3A4. After the 2-day treatment, CYP3A4 mRNA levels and testosterone 6β-hydroxylase activity were determined by real-time reverse transcription polymerase chain reaction and liquid chromatography-tandem mass spectrometry analysis, respectively. Our results demonstrated a strong and predictive relationship between the extent of midazolam AUC change in humans and the various parameters calculated from both CYP3A4 mRNA and enzyme activity. The relationships exhibited with non-midazolam in vivo probes, in aggregate, were unsatisfactory. In general, the models yielded better fits when unbound rather than total plasma Cmax was used to calculate the induction parameters, as evidenced by higher R(2) and lower root mean square error (RMSE) and geometric mean fold error. With midazolam, the R3 cut-off value of 0.9, as suggested by US Food and Drug Administration guidance, effectively categorized strong inducers but was less effective in classifying midrange or weak inducers. This study supports the use of calibration curves generated from in vitro mRNA induction response curves to predict CYP3A4 induction potential in human. With the caveat that most compounds evaluated here were not strong inhibitors of enzyme activity, testosterone 6β-hydroxylase activity was also demonstrated to be a strong predictor of CYP3A4 induction potential in this assay model.
    MeSH term(s) Area Under Curve ; Calibration ; Cells, Cultured ; Cryopreservation/methods ; Cytochrome P-450 CYP3A/genetics ; Cytochrome P-450 CYP3A/metabolism ; Enzyme Induction/genetics ; Hepatocytes/metabolism ; Humans ; Mixed Function Oxygenases/metabolism ; Pharmaceutical Preparations/administration & dosage ; Pharmaceutical Preparations/metabolism ; RNA, Messenger/genetics ; Testosterone/metabolism ; United States ; United States Food and Drug Administration
    Chemical Substances Pharmaceutical Preparations ; RNA, Messenger ; Testosterone (3XMK78S47O) ; Mixed Function Oxygenases (EC 1.-) ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; CYP3A4 protein, human (EC 1.14.14.55)
    Language English
    Publishing date 2014-06-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 186795-7
    ISSN 1521-009X ; 0090-9556
    ISSN (online) 1521-009X
    ISSN 0090-9556
    DOI 10.1124/dmd.114.058602
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1014: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article: CPX/D underestimates VO(2) in athletes compared with an automated Douglas bag system.

    Gore, Christopher J / Clark, Robert J / Shipp, Nicholas J / Van Der Ploeg, Grant E / Withers, Robert T

    Medicine and science in sports and exercise

    2003  Volume 35, Issue 8, Page(s) 1341–1347

    Abstract: Purpose: Based on persistent reports of low oxygen consumption VO(2) from Medical Graphics CPX/D metabolic carts, we compared the CPX/D against an automated Douglas bag system.: Methods: Twelve male athletes completed three, randomized 25-min bouts ( ... ...

    Abstract Purpose: Based on persistent reports of low oxygen consumption VO(2) from Medical Graphics CPX/D metabolic carts, we compared the CPX/D against an automated Douglas bag system.
    Methods: Twelve male athletes completed three, randomized 25-min bouts (5 min at 100, 150, 200, 250, and 300 W) on a cycle ergometer with intervening 30-min rests. One bout was measured on each of the CPX/D, the CPX/D with altered software (CPX/DDelta), and an automated Douglas bag system at Flinders University (FU). The CPX/DDelta software alteration was an apparent lag time correction factor of 60 ms.
    Results: For the CPX/D, both VO(2) and VCO(2) were significantly lower than the FU system at 100-300 W, and the relative differences ranged -10.7 to -12.0% and -7.7 to -8.2%, respectively. Altering the software approximately halved the VO(2) discrepancy between the CPX/DDelta and FU systems. When data from all five workloads were pooled, V(E) of the CPX/D (67.2 +/- 26.4 L x min-1) and CPX/DDelta (67.5 +/- 26.9 L x min-1) were significantly lower than for the FU system (70.5 +/- 27.1 L x min-1); and at 300 W, the relative differences were -4.0% and -3.4% for the CPX/D and CPX/DDelta, respectively. Altering the software changed the pooled %O(2) from 16.24 +/- 0.40% for the CPX/D to 16.04 +/- 0.39% for the CPX/DDelta, and these were significantly different than pooled data for the FU system (16.15 +/- 0.39%).
    Conclusions: During submaximal exercise, the CPX/D yields VO(2) values that are approximately 11% lower than the criterion system, and the source of the discrepancy does not appear to be primarily related to volume measurement. A disturbing observation is that factory defaults for the lag time use different correction factors, which vary by 60 ms and this significantly alters VO(2) and VCO(2).
    MeSH term(s) Adolescent ; Adult ; Carbon Dioxide/analysis ; Exercise/physiology ; Heart Rate/physiology ; Humans ; Male ; Oxygen Consumption/physiology ; Physiology/instrumentation ; Pulmonary Gas Exchange/physiology ; Sensitivity and Specificity ; Software ; Spirometry/instrumentation ; Sports Medicine/instrumentation
    Chemical Substances Carbon Dioxide (142M471B3J)
    Language English
    Publishing date 2003-08
    Publishing country United States
    Document type Clinical Trial ; Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 603994-7
    ISSN 1530-0315 ; 0195-9131 ; 0025-7990
    ISSN (online) 1530-0315
    ISSN 0195-9131 ; 0025-7990
    DOI 10.1249/01.MSS.0000079045.86512.C5
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 869: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Book: Black belt Korean karate

    Son, Duk Sung / Clark, Robert J.

    1983  

    Author's details Duk Sung Son & [and] Robert J. Clark
    Publisher Prentice-Hall; Englewood Cliffs, N.J.
    Document type Book
    HBZ-ID HT016783568
    ISBN 0-13-077669-6 ; 978-0-13-077669-3
    Database Central Library of Sport Science of the German Sport University Cologne

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  10. Article: Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite h152/81.

    Zhang, J George / Dehal, Shangara S / Ho, Thuy / Johnson, Jennifer / Chandler, Catherine / Blanchard, Andrew P / Clark, Robert J / Crespi, Charles L / Stresser, David M / Wong, James

    Drug metabolism and disposition: the biological fate of chemicals

    2006  Volume 34, Issue 5, Page(s) 734–737

    Abstract: Clevidipine is a short-acting dihydropyridine calcium channel antagonist under development for treatment of perioperative hypertension. Patients treated with clevidipine are likely to be comedicated. Therefore, the potential for clevidipine and its major ...

    Abstract Clevidipine is a short-acting dihydropyridine calcium channel antagonist under development for treatment of perioperative hypertension. Patients treated with clevidipine are likely to be comedicated. Therefore, the potential for clevidipine and its major metabolite H152/81 to elicit drug interactions by induction or inhibition of cytochrome P450 was investigated. Induction of CYP1A2, CYP2C9, and CYP3A4 was examined in primary human hepatocytes treated with clevidipine at 1, 10, and 100 microM. Clevidipine was found to be an inducer of CYP3A4, but not of CYP1A2 or CYP2C9, at the 10 microM and 100 microM concentrations of clevidipine tested. Induction response for CYP3A4 to 100 microM clevidipine was approximately 20% of that of the positive control inducer rifampicin. The response of H152/81 was similar. Using cDNA-expressed enzymes, clevidipine inhibited CYP2C9, CYP2C19, and CYP3A4 activities with IC(50) values below 10 microM, whereas CYP1A2, CYP2D6, and CYP2E1 activities were not substantially inhibited (IC(50) values >70 microM). The K(i) values for CYP2C9 and CYP2C19 were 1.7 and 3.3 microM, respectively, and those for CYP3A4 were 8.3 and 2.9 microM, using two substrates, testosterone and midazolam, respectively. These values are at least 10 times higher than the highest clevidipine concentration typically seen in the clinic. Little or no inhibition by H152/81 was found for the enzyme activities mentioned above (IC(50) values >or= 69 microM). The present study demonstrates that it is highly unlikely for clevidipine or its major metabolite to cause cytochrome P450-related drug interactions when used in the dose range required to manage hypertension in humans.
    MeSH term(s) Calcium Channel Blockers/pharmacology ; Cells, Cultured ; Child ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System/biosynthesis ; DNA, Complementary/biosynthesis ; DNA, Complementary/genetics ; Dihydropyridines/pharmacology ; Drug Interactions ; Enzyme Inhibitors/pharmacology ; Female ; Hepatocytes/drug effects ; Hepatocytes/enzymology ; Humans ; Isoenzymes/antagonists & inhibitors ; Male ; Middle Aged ; Pyridines/pharmacology
    Chemical Substances Calcium Channel Blockers ; Cytochrome P-450 Enzyme Inhibitors ; DNA, Complementary ; Dihydropyridines ; Enzyme Inhibitors ; Isoenzymes ; Pyridines ; monomethyl 4-(2',3'-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-2,5-dicarboxylate ; clevidipine (19O2GP3B7Q) ; Cytochrome P-450 Enzyme System (9035-51-2)
    Language English
    Publishing date 2006-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 186795-7
    ISSN 1521-009X ; 0090-9556
    ISSN (online) 1521-009X
    ISSN 0090-9556
    DOI 10.1124/dmd.105.006569
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1014: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top