The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
Douglas H. Sweet - One of the best experts on this subject based on the ideXlab platform.
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1 Human Organic Cation Transporters 1 (SLC22A1), 2 (SLC22A2), and 3 (SLC22A3) as 1 Disposition Pathways for Fluoroquinolone Antimicrobials 2 3
2016Co-Authors: Aditi Mulgaonkar, Dirk Gründemann, Jurgen Venitz, Douglas H. SweetAbstract:D ow nloaded from 2 Abstract 19 Fluoroquinolones (FQs) are important antimicrobials that exhibit activity against a wide 20 range of bacterial pathogens and excellent tissue permeation. They exist as charged molecules in 21 biological fluids and, thus, their disposition depends heavily on active transport and facilitative 22 diffusion. A recent review of the clinical literature indicated that tubular secretion and 23 reabsorption are major determinants of their half-life in plasma, efficacy, and drug-drug 24 interactions. In particular, published in vivo interactions between FQs and cationic drugs 25 affecting renal clearance implicated organic cation transporters (OCTs). In this study, thirteen 26 FQs, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, 27 norfloxacin, ofloxacin, pefloxacin, prulifloxacin, Rufloxacin and sparfloxacin, were screened for 28 their ability to inhibit transport activity of human OCT1 (SLC22A1), hOCT2 (SLC22A2), and 2
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human organic cation transporters 1 slc22a1 2 slc22a2 and 3 slc22a3 as disposition pathways for fluoroquinolone antimicrobials
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Aditi Mulgaonkar, Dirk Gründemann, Jurgen Venitz, Douglas H. SweetAbstract:ABSTRACT Fluoroquinolones (FQs) are important antimicrobials that exhibit activity against a wide range of bacterial pathogens and excellent tissue permeation. They exist as charged molecules in biological fluids, and thus, their disposition depends heavily on active transport and facilitative diffusion. A recent review of the clinical literature indicated that tubular secretion and reabsorption are major determinants of their half-life in plasma, efficacy, and drug-drug interactions. In particular, reported in vivo interactions between FQs and cationic drugs affecting renal clearance implicated organic cation transporters (OCTs). In this study, 13 FQs, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, prulifloxacin, Rufloxacin, and sparfloxacin, were screened for their ability to inhibit transport activity of human OCT1 (hOCT1) (SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3). All, with the exception of enoxacin, significantly inhibited hOCT1-mediated uptake under initial test conditions. None of the FQs inhibited hOCT2, and only moxifloxacin inhibited hOCT3 (∼30%), even at a 1,000-fold excess. Gatifloxacin, moxifloxacin, prulifloxacin, and sparfloxacin were determined to be competitive inhibitors of hOCT1. Inhibition constants ( K i ) were estimated to be 250 ± 18 μM, 161 ± 19 μM, 136 ± 33 μM, and 94 ± 8 μM, respectively. Moxifloxacin competitively inhibited hOCT3-mediated uptake, with a K i value of 1,598 ± 146 μM. Despite expression in enterocytes (luminal), hepatocytes (sinusoidal), and proximal tubule cells (basolateral), hOCT3 does not appear to contribute significantly to FQ disposition. However, hOCT1 in the sinusoidal membrane of hepatocytes, and potentially the basolateral membrane of proximal tubule cells, is likely to play a role in the disposition of these antimicrobial agents.
Aditi Mulgaonkar - One of the best experts on this subject based on the ideXlab platform.
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1 Human Organic Cation Transporters 1 (SLC22A1), 2 (SLC22A2), and 3 (SLC22A3) as 1 Disposition Pathways for Fluoroquinolone Antimicrobials 2 3
2016Co-Authors: Aditi Mulgaonkar, Dirk Gründemann, Jurgen Venitz, Douglas H. SweetAbstract:D ow nloaded from 2 Abstract 19 Fluoroquinolones (FQs) are important antimicrobials that exhibit activity against a wide 20 range of bacterial pathogens and excellent tissue permeation. They exist as charged molecules in 21 biological fluids and, thus, their disposition depends heavily on active transport and facilitative 22 diffusion. A recent review of the clinical literature indicated that tubular secretion and 23 reabsorption are major determinants of their half-life in plasma, efficacy, and drug-drug 24 interactions. In particular, published in vivo interactions between FQs and cationic drugs 25 affecting renal clearance implicated organic cation transporters (OCTs). In this study, thirteen 26 FQs, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, 27 norfloxacin, ofloxacin, pefloxacin, prulifloxacin, Rufloxacin and sparfloxacin, were screened for 28 their ability to inhibit transport activity of human OCT1 (SLC22A1), hOCT2 (SLC22A2), and 2
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human organic cation transporters 1 slc22a1 2 slc22a2 and 3 slc22a3 as disposition pathways for fluoroquinolone antimicrobials
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Aditi Mulgaonkar, Dirk Gründemann, Jurgen Venitz, Douglas H. SweetAbstract:ABSTRACT Fluoroquinolones (FQs) are important antimicrobials that exhibit activity against a wide range of bacterial pathogens and excellent tissue permeation. They exist as charged molecules in biological fluids, and thus, their disposition depends heavily on active transport and facilitative diffusion. A recent review of the clinical literature indicated that tubular secretion and reabsorption are major determinants of their half-life in plasma, efficacy, and drug-drug interactions. In particular, reported in vivo interactions between FQs and cationic drugs affecting renal clearance implicated organic cation transporters (OCTs). In this study, 13 FQs, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, prulifloxacin, Rufloxacin, and sparfloxacin, were screened for their ability to inhibit transport activity of human OCT1 (hOCT1) (SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3). All, with the exception of enoxacin, significantly inhibited hOCT1-mediated uptake under initial test conditions. None of the FQs inhibited hOCT2, and only moxifloxacin inhibited hOCT3 (∼30%), even at a 1,000-fold excess. Gatifloxacin, moxifloxacin, prulifloxacin, and sparfloxacin were determined to be competitive inhibitors of hOCT1. Inhibition constants ( K i ) were estimated to be 250 ± 18 μM, 161 ± 19 μM, 136 ± 33 μM, and 94 ± 8 μM, respectively. Moxifloxacin competitively inhibited hOCT3-mediated uptake, with a K i value of 1,598 ± 146 μM. Despite expression in enterocytes (luminal), hepatocytes (sinusoidal), and proximal tubule cells (basolateral), hOCT3 does not appear to contribute significantly to FQ disposition. However, hOCT1 in the sinusoidal membrane of hepatocytes, and potentially the basolateral membrane of proximal tubule cells, is likely to play a role in the disposition of these antimicrobial agents.
A. De Sarro - One of the best experts on this subject based on the ideXlab platform.
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Effects of Novel 6-Desfluoroquinolones and Classic Quinolones on Pentylenetetrazole-Induced Seizures in Mice
Antimicrobial Agents and Chemotherapy, 1999Co-Authors: A. De Sarro, Violetta Cecchetti, V. Fravolini, F. Naccari, Oriana Tabarrini, G. B. De SarroAbstract:There have been several reports that convulsions, although rare, occur in patients who receive fluoroquinolones. In this study, the proconvulsant effects exhibited by a novel series of 6-desfluoroquinolones and some classic quinolones on pentylenetetrazole (PTZ)-induced seizures in mice were evaluated and compared. Animals were intraperitoneally injected with vehicle or quinolone derivatives (5 to 100 μg/g of body weight) 30 min before the subcutaneous (s.c.) administration of PTZ (40 μg/g). In each experiment, mice were then observed for 1 h to monitor for the incidence and onset of clonic seizures. The order of proconvulsant activity in our epileptic model was MF5184 > MF5187 > pefloxacin > MF5189 > ofloxacin > ciprofloxacin > MF5140 > MF5181 > MF5137 > Rufloxacin > MF5143 > MF5158 > MF5191 > MF5128 > MF5138 > cinoxacin > MF5142 > norfloxacin > nalidixic acid. The relationship between the chemical structure and the proconvulsant activity of 6-desfluoroquinolone derivatives was studied. We observed that, in terms of toxicity to the central nervous system (CNS), besides the heterocyclic side chain (moiety) at the C-7 position, the C-6 substituent also appears to play an important role. In particular, a hydrogen at the C-6 position seemed to be responsible for major neurotoxic activity in comparison to an amino group located in the same position. The relationship between lipophilicity and proconvulsant activity was also investigated. We did not find any clear relationship between a higher level of lipophilicity and major proconvulsant properties. Although the principal mechanism by which quinolones induce potentiation of the proconvulsant effects of PTZ cannot be easily determined, it is possible that the convulsions are caused by drug interactions, because both PTZ and quinolones are believed to increase excitation of the CNS by inhibition of γ-aminobutyric acid binding to receptors.
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Quinolones potentiate cefazolin-induced seizures in DBA/2 mice.
Antimicrobial agents and chemotherapy, 1993Co-Authors: A. De Sarro, Maria Zappalà, Alba Chimirri, Silvana Grasso, G. De SarroAbstract:The behavioral and convulsant effects of cefazolin, a beta-lactam derivative, were studied after intraperitoneal administration to DBA/2 mice, a strain genetically susceptible to sound-induced seizures, and Swiss mice. DBA/2 mice were more susceptible to seizures induced by cefazolin than were Swiss mice. The proconvulsant effects of some quinolones on seizures evoked by intraperitoneal administration of cefazolin were also evaluated in DBA/2 mice. Our study also demonstrated that the order of proconvulsant activity in our epileptic model was pefloxacin > enoxacin > ofloxacin > Rufloxacin > norfloxacin > cinoxacin > ciprofloxacin > nalidixic acid. The relationships between the chemical structures and proconvulsant activities of quinolone derivatives were studied. The relationship between lipophilicity and proconvulsant activity was also investigated.
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Quinolones potentiate cefazolin-induced seizures in DBA/2 mice. Antimicrob. Agents Chemother
1993Co-Authors: A. De Sarro, Maria Zappalà, Alba Chimirri, Silvana Grasso, G. B. De SarroAbstract:The behavioral and convulsant effects of cefazolin, a I-lactam derivative, were studied after intraperitoneal administration to DBA/2 mice, a strain genetically susceptible to sound-induced seizures, and Swiss mice. DBA/2 mice were more susceptible to seizures induced by cefazolin than were Swiss mice. The proconvulsant effects of some quinolones on seizures evoked by intraperitoneal administration of cefazolin were also evaluated in DBA/2 mice. Our study also demonstrated that the order of proconvulsant activity in our epileptic model was pefloxacin> enoxacin> ofloxacin> Rufloxacin> norfloxacin> cinoxacin> ciprofloxacin> nalidixic acid. The relationships between the chemical structures and proconvulsant activities of quinolone derivatives were studied. The relationship between lipophilicity and proconvulsant activity was also investigated. The genetically epilepsy-prone mouse or Dilute Brown Agouti DBA/2J (DBA/2) mouse has been known since 1947 to be a strain susceptible to audiogenic seizures (AGSs) (21). The characteristics and neurochemical abnormalities of this mouse strain have been described by various researchers (6, 35, 36, 40). Between 16 and 30 days of age in response to a loud tone, this mouse strain shows ill-coordinated locomo
Dirk Gründemann - One of the best experts on this subject based on the ideXlab platform.
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1 Human Organic Cation Transporters 1 (SLC22A1), 2 (SLC22A2), and 3 (SLC22A3) as 1 Disposition Pathways for Fluoroquinolone Antimicrobials 2 3
2016Co-Authors: Aditi Mulgaonkar, Dirk Gründemann, Jurgen Venitz, Douglas H. SweetAbstract:D ow nloaded from 2 Abstract 19 Fluoroquinolones (FQs) are important antimicrobials that exhibit activity against a wide 20 range of bacterial pathogens and excellent tissue permeation. They exist as charged molecules in 21 biological fluids and, thus, their disposition depends heavily on active transport and facilitative 22 diffusion. A recent review of the clinical literature indicated that tubular secretion and 23 reabsorption are major determinants of their half-life in plasma, efficacy, and drug-drug 24 interactions. In particular, published in vivo interactions between FQs and cationic drugs 25 affecting renal clearance implicated organic cation transporters (OCTs). In this study, thirteen 26 FQs, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, 27 norfloxacin, ofloxacin, pefloxacin, prulifloxacin, Rufloxacin and sparfloxacin, were screened for 28 their ability to inhibit transport activity of human OCT1 (SLC22A1), hOCT2 (SLC22A2), and 2
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human organic cation transporters 1 slc22a1 2 slc22a2 and 3 slc22a3 as disposition pathways for fluoroquinolone antimicrobials
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Aditi Mulgaonkar, Dirk Gründemann, Jurgen Venitz, Douglas H. SweetAbstract:ABSTRACT Fluoroquinolones (FQs) are important antimicrobials that exhibit activity against a wide range of bacterial pathogens and excellent tissue permeation. They exist as charged molecules in biological fluids, and thus, their disposition depends heavily on active transport and facilitative diffusion. A recent review of the clinical literature indicated that tubular secretion and reabsorption are major determinants of their half-life in plasma, efficacy, and drug-drug interactions. In particular, reported in vivo interactions between FQs and cationic drugs affecting renal clearance implicated organic cation transporters (OCTs). In this study, 13 FQs, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, prulifloxacin, Rufloxacin, and sparfloxacin, were screened for their ability to inhibit transport activity of human OCT1 (hOCT1) (SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3). All, with the exception of enoxacin, significantly inhibited hOCT1-mediated uptake under initial test conditions. None of the FQs inhibited hOCT2, and only moxifloxacin inhibited hOCT3 (∼30%), even at a 1,000-fold excess. Gatifloxacin, moxifloxacin, prulifloxacin, and sparfloxacin were determined to be competitive inhibitors of hOCT1. Inhibition constants ( K i ) were estimated to be 250 ± 18 μM, 161 ± 19 μM, 136 ± 33 μM, and 94 ± 8 μM, respectively. Moxifloxacin competitively inhibited hOCT3-mediated uptake, with a K i value of 1,598 ± 146 μM. Despite expression in enterocytes (luminal), hepatocytes (sinusoidal), and proximal tubule cells (basolateral), hOCT3 does not appear to contribute significantly to FQ disposition. However, hOCT1 in the sinusoidal membrane of hepatocytes, and potentially the basolateral membrane of proximal tubule cells, is likely to play a role in the disposition of these antimicrobial agents.
Jurgen Venitz - One of the best experts on this subject based on the ideXlab platform.
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1 Human Organic Cation Transporters 1 (SLC22A1), 2 (SLC22A2), and 3 (SLC22A3) as 1 Disposition Pathways for Fluoroquinolone Antimicrobials 2 3
2016Co-Authors: Aditi Mulgaonkar, Dirk Gründemann, Jurgen Venitz, Douglas H. SweetAbstract:D ow nloaded from 2 Abstract 19 Fluoroquinolones (FQs) are important antimicrobials that exhibit activity against a wide 20 range of bacterial pathogens and excellent tissue permeation. They exist as charged molecules in 21 biological fluids and, thus, their disposition depends heavily on active transport and facilitative 22 diffusion. A recent review of the clinical literature indicated that tubular secretion and 23 reabsorption are major determinants of their half-life in plasma, efficacy, and drug-drug 24 interactions. In particular, published in vivo interactions between FQs and cationic drugs 25 affecting renal clearance implicated organic cation transporters (OCTs). In this study, thirteen 26 FQs, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, 27 norfloxacin, ofloxacin, pefloxacin, prulifloxacin, Rufloxacin and sparfloxacin, were screened for 28 their ability to inhibit transport activity of human OCT1 (SLC22A1), hOCT2 (SLC22A2), and 2
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human organic cation transporters 1 slc22a1 2 slc22a2 and 3 slc22a3 as disposition pathways for fluoroquinolone antimicrobials
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Aditi Mulgaonkar, Dirk Gründemann, Jurgen Venitz, Douglas H. SweetAbstract:ABSTRACT Fluoroquinolones (FQs) are important antimicrobials that exhibit activity against a wide range of bacterial pathogens and excellent tissue permeation. They exist as charged molecules in biological fluids, and thus, their disposition depends heavily on active transport and facilitative diffusion. A recent review of the clinical literature indicated that tubular secretion and reabsorption are major determinants of their half-life in plasma, efficacy, and drug-drug interactions. In particular, reported in vivo interactions between FQs and cationic drugs affecting renal clearance implicated organic cation transporters (OCTs). In this study, 13 FQs, ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, prulifloxacin, Rufloxacin, and sparfloxacin, were screened for their ability to inhibit transport activity of human OCT1 (hOCT1) (SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3). All, with the exception of enoxacin, significantly inhibited hOCT1-mediated uptake under initial test conditions. None of the FQs inhibited hOCT2, and only moxifloxacin inhibited hOCT3 (∼30%), even at a 1,000-fold excess. Gatifloxacin, moxifloxacin, prulifloxacin, and sparfloxacin were determined to be competitive inhibitors of hOCT1. Inhibition constants ( K i ) were estimated to be 250 ± 18 μM, 161 ± 19 μM, 136 ± 33 μM, and 94 ± 8 μM, respectively. Moxifloxacin competitively inhibited hOCT3-mediated uptake, with a K i value of 1,598 ± 146 μM. Despite expression in enterocytes (luminal), hepatocytes (sinusoidal), and proximal tubule cells (basolateral), hOCT3 does not appear to contribute significantly to FQ disposition. However, hOCT1 in the sinusoidal membrane of hepatocytes, and potentially the basolateral membrane of proximal tubule cells, is likely to play a role in the disposition of these antimicrobial agents.
