The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
Fritz Sörgel - One of the best experts on this subject based on the ideXlab platform.
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competitive inhibition of renal tubular secretion of ciprofloxacin and metabolite by Probenecid
British Journal of Clinical Pharmacology, 2010Co-Authors: Cornelia B. Landersdorfer, Carl M. J. Kirkpatrick, Martina Kinzig, Jürgen B. Bulitta, Ulrike Holzgrabe, Ulrich Jaehde, Andreas Reiter, Kurt G Naber, Michael Rodamer, Fritz SörgelAbstract:Aims Probenecid influences transport processes of drugs at several sites in the body and decreases elimination of several quinolones. We sought to explore extent, time course, and mechanism of the interaction between ciprofloxacin and Probenecid at renal and nonrenal sites. Methods A randomized, two-way crossover study was conducted in 12 healthy volunteers (in part previously published Clin Pharmacol Ther 1995; 58: 532-41). Subjects received 200 mg ciprofloxacin as 30-min intravenous infusion without and with 3 g Probenecid divided into five oral doses. Drug concentrations were analysed by liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography. Ciprofloxacin and its 2-aminoethylamino-metabolite (M1) in plasma and urine with and without Probenecid were modelled simultaneously with WinNonlin. Results Data are ratio of geometric means (90% confidence intervals). Addition of Probenecid reduced the median renal clearance from 23.8 to 8.25 l h(-1)[65% reduction (59, 71), P Conclusions Probenecid inhibited the renal tubular secretion of ciprofloxacin and M1, probably by a competitive mechanism and due to reaching >100-fold higher plasma concentrations. Formation of M1, nonrenal clearance and distribution of ciprofloxacin were not affected.
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Competitive inhibition of renal tubular secretion of gemifloxacin by Probenecid
Antimicrobial agents and chemotherapy, 2009Co-Authors: Cornelia B. Landersdorfer, Carl M. J. Kirkpatrick, Martina Kinzig, Jürgen B. Bulitta, Ulrike Holzgrabe, George L. Drusano, Fritz SörgelAbstract:Probenecid interacts with transport processes of drugs at several sites in the body. For most quinolones, renal clearance is reduced by concomitant administration of Probenecid. The interaction between gemifloxacin and Probenecid has not yet been studied. We studied the extent, time course, site(s), and mechanism of this interaction. Seventeen healthy volunteers participated in a randomized, two-way crossover study. Subjects received 320 mg gemifloxacin as an oral tablet without and with 4.5 g Probenecid divided in eight oral doses. Drug concentrations in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry. WinNonlin was used for noncompartmental analysis, compartmental modeling, and statistics, and NONMEM was used for visual predictive checks. Concomitant administration of Probenecid increased plasma gemifloxacin concentrations and amounts excreted in urine compared to baseline amounts. Data are average estimates (percent coefficients of variation). Modeling showed a competitive inhibition of the renal tubular secretion of gemifloxacin by Probenecid as the most likely mechanism of the interaction. The estimated K m and V max for the saturable part of renal elimination were 9.16 mg/liter (20%) and 113 mg/h (21%), respectively. Based on the molar ratio, the affinity for the renal transporter was 10-fold higher for gemifloxacin than for Probenecid. Since Probenecid reached an ∼200-times-higher area under the molar concentration-time curve from 0 to 24 h than gemifloxacin, Probenecid inhibited the active tubular secretion of gemifloxacin. Probenecid also reduced the nonrenal clearance of gemifloxacin from 25.2 (26%) to 21.0 (23%) liters/h. Probenecid inhibited the renal tubular secretion of gemifloxacin, most likely by a competitive mechanism, and slightly decreased nonrenal clearance of gemifloxacin.
Leigh Anne Swayne - One of the best experts on this subject based on the ideXlab platform.
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Probenecid disrupts a novel pannexin 1 collapsin response mediator protein 2 interaction and increases microtubule stability
Frontiers in Cellular Neuroscience, 2018Co-Authors: Leigh E Wickistordeur, Juan C Sanchezarias, Mei Liu, Maria S Weaver, Catherine S W Choi, Leigh Anne SwayneAbstract:Neurite formation relies on finely-tuned control of the cytoskeleton. Here we identified a novel protein-protein interaction between the ion and metabolite channel protein Pannexin 1 (Panx1) and collapsin response mediator protein 2 (Crmp2), a positive regulator of microtubule polymerization and stabilization. Panx1 and Crmp2 co-precipitated from both Neuro-2a (N2a) cells and mouse ventricular zone (VZ) tissue. In vitro binding assays between purified proteins revealed the interaction occurs directly between the Panx1 C-terminus (Panx1 CT) and Crmp2. Because Crmp2 is a well-established microtubule-stabilizing protein, and we previously observed a marked increase in neurite formation following treatment with the Panx1 blocker, Probenecid, in N2a cells and VZ neural precursor cells (NPCs), we investigated the impact of Probenecid on the Panx1-Crmp2 interaction. Probenecid treatment significantly disrupted the Panx1-Crmp2 interaction by both immunoprecipitation (IP) and proximity ligation analysis, without altering overall Crmp2 protein expression levels. In the presence of Probenecid, Crmp2 was concentrated at the distal ends of growing neurites. Moreover, Probenecid treatment increased tubulin polymerization and microtubule stability in N2a cells. These results reveal that Probenecid disrupts a novel interaction between Panx1 and the microtubule stabilizer, Crmp2, and also increases microtubule stability.
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Presentation_1_Probenecid Disrupts a Novel Pannexin 1-Collapsin Response Mediator Protein 2 Interaction and Increases Microtubule Stability.PDF
2018Co-Authors: Leigh E. Wicki-stordeur, Mei Liu, Maria S Weaver, Catherine S W Choi, Juan C. Sanchez-arias, Leigh Anne SwayneAbstract:Neurite formation relies on finely-tuned control of the cytoskeleton. Here we identified a novel protein-protein interaction between the ion and metabolite channel protein Pannexin 1 (Panx1) and collapsin response mediator protein 2 (Crmp2), a positive regulator of microtubule polymerization and stabilization. Panx1 and Crmp2 co-precipitated from both Neuro-2a (N2a) cells and mouse ventricular zone (VZ) tissue. In vitro binding assays between purified proteins revealed the interaction occurs directly between the Panx1 C-terminus (Panx1 CT) and Crmp2. Because Crmp2 is a well-established microtubule-stabilizing protein, and we previously observed a marked increase in neurite formation following treatment with the Panx1 blocker, Probenecid, in N2a cells and VZ neural precursor cells (NPCs), we investigated the impact of Probenecid on the Panx1-Crmp2 interaction. Probenecid treatment significantly disrupted the Panx1-Crmp2 interaction by both immunoprecipitation (IP) and proximity ligation analysis, without altering overall Crmp2 protein expression levels. In the presence of Probenecid, Crmp2 was concentrated at the distal ends of growing neurites. Moreover, Probenecid treatment increased tubulin polymerization and microtubule stability in N2a cells. These results reveal that Probenecid disrupts a novel interaction between Panx1 and the microtubule stabilizer, Crmp2, and also increases microtubule stability.
Cornelia B. Landersdorfer - One of the best experts on this subject based on the ideXlab platform.
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competitive inhibition of renal tubular secretion of ciprofloxacin and metabolite by Probenecid
British Journal of Clinical Pharmacology, 2010Co-Authors: Cornelia B. Landersdorfer, Carl M. J. Kirkpatrick, Martina Kinzig, Jürgen B. Bulitta, Ulrike Holzgrabe, Ulrich Jaehde, Andreas Reiter, Kurt G Naber, Michael Rodamer, Fritz SörgelAbstract:Aims Probenecid influences transport processes of drugs at several sites in the body and decreases elimination of several quinolones. We sought to explore extent, time course, and mechanism of the interaction between ciprofloxacin and Probenecid at renal and nonrenal sites. Methods A randomized, two-way crossover study was conducted in 12 healthy volunteers (in part previously published Clin Pharmacol Ther 1995; 58: 532-41). Subjects received 200 mg ciprofloxacin as 30-min intravenous infusion without and with 3 g Probenecid divided into five oral doses. Drug concentrations were analysed by liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography. Ciprofloxacin and its 2-aminoethylamino-metabolite (M1) in plasma and urine with and without Probenecid were modelled simultaneously with WinNonlin. Results Data are ratio of geometric means (90% confidence intervals). Addition of Probenecid reduced the median renal clearance from 23.8 to 8.25 l h(-1)[65% reduction (59, 71), P Conclusions Probenecid inhibited the renal tubular secretion of ciprofloxacin and M1, probably by a competitive mechanism and due to reaching >100-fold higher plasma concentrations. Formation of M1, nonrenal clearance and distribution of ciprofloxacin were not affected.
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Competitive inhibition of renal tubular secretion of gemifloxacin by Probenecid
Antimicrobial agents and chemotherapy, 2009Co-Authors: Cornelia B. Landersdorfer, Carl M. J. Kirkpatrick, Martina Kinzig, Jürgen B. Bulitta, Ulrike Holzgrabe, George L. Drusano, Fritz SörgelAbstract:Probenecid interacts with transport processes of drugs at several sites in the body. For most quinolones, renal clearance is reduced by concomitant administration of Probenecid. The interaction between gemifloxacin and Probenecid has not yet been studied. We studied the extent, time course, site(s), and mechanism of this interaction. Seventeen healthy volunteers participated in a randomized, two-way crossover study. Subjects received 320 mg gemifloxacin as an oral tablet without and with 4.5 g Probenecid divided in eight oral doses. Drug concentrations in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry. WinNonlin was used for noncompartmental analysis, compartmental modeling, and statistics, and NONMEM was used for visual predictive checks. Concomitant administration of Probenecid increased plasma gemifloxacin concentrations and amounts excreted in urine compared to baseline amounts. Data are average estimates (percent coefficients of variation). Modeling showed a competitive inhibition of the renal tubular secretion of gemifloxacin by Probenecid as the most likely mechanism of the interaction. The estimated K m and V max for the saturable part of renal elimination were 9.16 mg/liter (20%) and 113 mg/h (21%), respectively. Based on the molar ratio, the affinity for the renal transporter was 10-fold higher for gemifloxacin than for Probenecid. Since Probenecid reached an ∼200-times-higher area under the molar concentration-time curve from 0 to 24 h than gemifloxacin, Probenecid inhibited the active tubular secretion of gemifloxacin. Probenecid also reduced the nonrenal clearance of gemifloxacin from 25.2 (26%) to 21.0 (23%) liters/h. Probenecid inhibited the renal tubular secretion of gemifloxacin, most likely by a competitive mechanism, and slightly decreased nonrenal clearance of gemifloxacin.
Ulrike Holzgrabe - One of the best experts on this subject based on the ideXlab platform.
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competitive inhibition of renal tubular secretion of ciprofloxacin and metabolite by Probenecid
British Journal of Clinical Pharmacology, 2010Co-Authors: Cornelia B. Landersdorfer, Carl M. J. Kirkpatrick, Martina Kinzig, Jürgen B. Bulitta, Ulrike Holzgrabe, Ulrich Jaehde, Andreas Reiter, Kurt G Naber, Michael Rodamer, Fritz SörgelAbstract:Aims Probenecid influences transport processes of drugs at several sites in the body and decreases elimination of several quinolones. We sought to explore extent, time course, and mechanism of the interaction between ciprofloxacin and Probenecid at renal and nonrenal sites. Methods A randomized, two-way crossover study was conducted in 12 healthy volunteers (in part previously published Clin Pharmacol Ther 1995; 58: 532-41). Subjects received 200 mg ciprofloxacin as 30-min intravenous infusion without and with 3 g Probenecid divided into five oral doses. Drug concentrations were analysed by liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography. Ciprofloxacin and its 2-aminoethylamino-metabolite (M1) in plasma and urine with and without Probenecid were modelled simultaneously with WinNonlin. Results Data are ratio of geometric means (90% confidence intervals). Addition of Probenecid reduced the median renal clearance from 23.8 to 8.25 l h(-1)[65% reduction (59, 71), P Conclusions Probenecid inhibited the renal tubular secretion of ciprofloxacin and M1, probably by a competitive mechanism and due to reaching >100-fold higher plasma concentrations. Formation of M1, nonrenal clearance and distribution of ciprofloxacin were not affected.
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Competitive inhibition of renal tubular secretion of gemifloxacin by Probenecid
Antimicrobial agents and chemotherapy, 2009Co-Authors: Cornelia B. Landersdorfer, Carl M. J. Kirkpatrick, Martina Kinzig, Jürgen B. Bulitta, Ulrike Holzgrabe, George L. Drusano, Fritz SörgelAbstract:Probenecid interacts with transport processes of drugs at several sites in the body. For most quinolones, renal clearance is reduced by concomitant administration of Probenecid. The interaction between gemifloxacin and Probenecid has not yet been studied. We studied the extent, time course, site(s), and mechanism of this interaction. Seventeen healthy volunteers participated in a randomized, two-way crossover study. Subjects received 320 mg gemifloxacin as an oral tablet without and with 4.5 g Probenecid divided in eight oral doses. Drug concentrations in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry. WinNonlin was used for noncompartmental analysis, compartmental modeling, and statistics, and NONMEM was used for visual predictive checks. Concomitant administration of Probenecid increased plasma gemifloxacin concentrations and amounts excreted in urine compared to baseline amounts. Data are average estimates (percent coefficients of variation). Modeling showed a competitive inhibition of the renal tubular secretion of gemifloxacin by Probenecid as the most likely mechanism of the interaction. The estimated K m and V max for the saturable part of renal elimination were 9.16 mg/liter (20%) and 113 mg/h (21%), respectively. Based on the molar ratio, the affinity for the renal transporter was 10-fold higher for gemifloxacin than for Probenecid. Since Probenecid reached an ∼200-times-higher area under the molar concentration-time curve from 0 to 24 h than gemifloxacin, Probenecid inhibited the active tubular secretion of gemifloxacin. Probenecid also reduced the nonrenal clearance of gemifloxacin from 25.2 (26%) to 21.0 (23%) liters/h. Probenecid inhibited the renal tubular secretion of gemifloxacin, most likely by a competitive mechanism, and slightly decreased nonrenal clearance of gemifloxacin.
Jürgen B. Bulitta - One of the best experts on this subject based on the ideXlab platform.
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competitive inhibition of renal tubular secretion of ciprofloxacin and metabolite by Probenecid
British Journal of Clinical Pharmacology, 2010Co-Authors: Cornelia B. Landersdorfer, Carl M. J. Kirkpatrick, Martina Kinzig, Jürgen B. Bulitta, Ulrike Holzgrabe, Ulrich Jaehde, Andreas Reiter, Kurt G Naber, Michael Rodamer, Fritz SörgelAbstract:Aims Probenecid influences transport processes of drugs at several sites in the body and decreases elimination of several quinolones. We sought to explore extent, time course, and mechanism of the interaction between ciprofloxacin and Probenecid at renal and nonrenal sites. Methods A randomized, two-way crossover study was conducted in 12 healthy volunteers (in part previously published Clin Pharmacol Ther 1995; 58: 532-41). Subjects received 200 mg ciprofloxacin as 30-min intravenous infusion without and with 3 g Probenecid divided into five oral doses. Drug concentrations were analysed by liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography. Ciprofloxacin and its 2-aminoethylamino-metabolite (M1) in plasma and urine with and without Probenecid were modelled simultaneously with WinNonlin. Results Data are ratio of geometric means (90% confidence intervals). Addition of Probenecid reduced the median renal clearance from 23.8 to 8.25 l h(-1)[65% reduction (59, 71), P Conclusions Probenecid inhibited the renal tubular secretion of ciprofloxacin and M1, probably by a competitive mechanism and due to reaching >100-fold higher plasma concentrations. Formation of M1, nonrenal clearance and distribution of ciprofloxacin were not affected.
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Competitive inhibition of renal tubular secretion of gemifloxacin by Probenecid
Antimicrobial agents and chemotherapy, 2009Co-Authors: Cornelia B. Landersdorfer, Carl M. J. Kirkpatrick, Martina Kinzig, Jürgen B. Bulitta, Ulrike Holzgrabe, George L. Drusano, Fritz SörgelAbstract:Probenecid interacts with transport processes of drugs at several sites in the body. For most quinolones, renal clearance is reduced by concomitant administration of Probenecid. The interaction between gemifloxacin and Probenecid has not yet been studied. We studied the extent, time course, site(s), and mechanism of this interaction. Seventeen healthy volunteers participated in a randomized, two-way crossover study. Subjects received 320 mg gemifloxacin as an oral tablet without and with 4.5 g Probenecid divided in eight oral doses. Drug concentrations in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry. WinNonlin was used for noncompartmental analysis, compartmental modeling, and statistics, and NONMEM was used for visual predictive checks. Concomitant administration of Probenecid increased plasma gemifloxacin concentrations and amounts excreted in urine compared to baseline amounts. Data are average estimates (percent coefficients of variation). Modeling showed a competitive inhibition of the renal tubular secretion of gemifloxacin by Probenecid as the most likely mechanism of the interaction. The estimated K m and V max for the saturable part of renal elimination were 9.16 mg/liter (20%) and 113 mg/h (21%), respectively. Based on the molar ratio, the affinity for the renal transporter was 10-fold higher for gemifloxacin than for Probenecid. Since Probenecid reached an ∼200-times-higher area under the molar concentration-time curve from 0 to 24 h than gemifloxacin, Probenecid inhibited the active tubular secretion of gemifloxacin. Probenecid also reduced the nonrenal clearance of gemifloxacin from 25.2 (26%) to 21.0 (23%) liters/h. Probenecid inhibited the renal tubular secretion of gemifloxacin, most likely by a competitive mechanism, and slightly decreased nonrenal clearance of gemifloxacin.
