The Experts below are selected from a list of 14130 Experts worldwide ranked by ideXlab platform
Bernard Faller - One of the best experts on this subject based on the ideXlab platform.
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high throughput permeability ph profile and high throughput alkane water log p with Artificial Membranes
Journal of Medicinal Chemistry, 2001Co-Authors: Frank Wohnsland, Bernard FallerAbstract:This study reports on a novel, high-throughput assay, designed to predict passive, transcellular permeability in early drug discovery. The assay is carried out in 96-well microtiterplates and measures the ability of compounds to diffuse from a donor to an acceptor compartment which are separated by a 9-10 microm hexadecane liquid layer. A set of 32 well-characterized, chemically diverse drugs was used to validate the method. The permeability values derived from the flux factors between donor and acceptor compartments show a good correlation with gastrointestinal absorption in humans. For comparison, correlations based on experimental or calculated octanol/water distribution coefficients (log D(o/w,6.8)) were significantly lower. In addition, this simple and robust assay allows determination of pH permeability profiles, critical information to predict gastrointestinal absorption of ionizable drugs and difficult to obtain from cell culture experiments. Correction for the unstirred water layer effect allows to differentiate between effective and intrinsic membrane permeability and opens up the dynamic range of the method. In addition, alkane/water partition coefficients can be derived from intrinsic membrane permeabilities, making this assay the first high-throughput method able to measure alkane/water log P in the microtiterplate format.
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high throughput permeability ph profile and high throughput alkane water log p with Artificial Membranes
Journal of Medicinal Chemistry, 2001Co-Authors: Frank Wohnsland, Bernard FallerAbstract:This study reports on a novel, high-throughput assay, designed to predict passive, transcellular permeability in early drug discovery. The assay is carried out in 96-well microtiterplates and measures the ability of compounds to diffuse from a donor to an acceptor compartment which are separated by a 9−10 μm hexadecane liquid layer. A set of 32 well-characterized, chemically diverse drugs was used to validate the method. The permeability values derived from the flux factors between donor and acceptor compartments show a good correlation with gastrointestinal absorption in humans. For comparison, correlations based on experimental or calculated octanol/water distribution coefficients (log Do/w,6.8) were significantly lower. In addition, this simple and robust assay allows determination of pH permeability profiles, critical information to predict gastrointestinal absorption of ionizable drugs and difficult to obtain from cell culture experiments. Correction for the unstirred water layer effect allows to dif...
Frank Wohnsland - One of the best experts on this subject based on the ideXlab platform.
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high throughput permeability ph profile and high throughput alkane water log p with Artificial Membranes
Journal of Medicinal Chemistry, 2001Co-Authors: Frank Wohnsland, Bernard FallerAbstract:This study reports on a novel, high-throughput assay, designed to predict passive, transcellular permeability in early drug discovery. The assay is carried out in 96-well microtiterplates and measures the ability of compounds to diffuse from a donor to an acceptor compartment which are separated by a 9-10 microm hexadecane liquid layer. A set of 32 well-characterized, chemically diverse drugs was used to validate the method. The permeability values derived from the flux factors between donor and acceptor compartments show a good correlation with gastrointestinal absorption in humans. For comparison, correlations based on experimental or calculated octanol/water distribution coefficients (log D(o/w,6.8)) were significantly lower. In addition, this simple and robust assay allows determination of pH permeability profiles, critical information to predict gastrointestinal absorption of ionizable drugs and difficult to obtain from cell culture experiments. Correction for the unstirred water layer effect allows to differentiate between effective and intrinsic membrane permeability and opens up the dynamic range of the method. In addition, alkane/water partition coefficients can be derived from intrinsic membrane permeabilities, making this assay the first high-throughput method able to measure alkane/water log P in the microtiterplate format.
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high throughput permeability ph profile and high throughput alkane water log p with Artificial Membranes
Journal of Medicinal Chemistry, 2001Co-Authors: Frank Wohnsland, Bernard FallerAbstract:This study reports on a novel, high-throughput assay, designed to predict passive, transcellular permeability in early drug discovery. The assay is carried out in 96-well microtiterplates and measures the ability of compounds to diffuse from a donor to an acceptor compartment which are separated by a 9−10 μm hexadecane liquid layer. A set of 32 well-characterized, chemically diverse drugs was used to validate the method. The permeability values derived from the flux factors between donor and acceptor compartments show a good correlation with gastrointestinal absorption in humans. For comparison, correlations based on experimental or calculated octanol/water distribution coefficients (log Do/w,6.8) were significantly lower. In addition, this simple and robust assay allows determination of pH permeability profiles, critical information to predict gastrointestinal absorption of ionizable drugs and difficult to obtain from cell culture experiments. Correction for the unstirred water layer effect allows to dif...
Frans Jongejan - One of the best experts on this subject based on the ideXlab platform.
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transmission of ehrlichia canis by rhipicephalus sanguineus ticks feeding on dogs and on Artificial Membranes
Veterinary Parasitology, 2013Co-Authors: Josephus J Fourie, Dorothee Stanneck, Herman G Luus, Frederic Beugnet, Michiel Wijnveld, Frans JongejanAbstract:A South African strain of Ehrlichia canis was isolated and used to infect a laboratory-bred Beagle dog. Rhipicephalus sanguineus nymphs, which fed on this dog, moulted to adult ticks which carried infection rates of E. canis between 12% and 19% and were used in a series of in vivo and in vitro experiments. Five groups of 6 dogs were challenged with the infected R. sanguineus ticks, which were removed 24h, 12h, 6h or 3h after the ticks had been released onto the dogs. The animals were monitored for fever and thrombocytopenia and were considered infected if they became serologically positive for E. canis antibodies as well as PCR positive for E. canis DNA. Seven dogs became infected with E. canis in the following groups: Group 1 (24h tick challenge) 1 out of 6; Group 2 (12h) 1 of 6; Group 3 (6h) 2 of 6; Group 4 (6h) 2 of 6 and Group 5 (3h) 1 out of 6. Six of those 7 infected dogs developed fever and a significant thrombocytopenia. One dog did not show any symptoms, but seroconverted and was found PCR positive on several occasions. Five additional dogs were PCR positive on one test sample only but were not considered infected because they did not develop any specific E. canis antibodies. In vitro, R. sanguineus ticks attached and fed on bovine blood through silicone Membranes with attachment rates up to 72.5% after 24h increasing to 84.2% at 72 h. The ticks transmitted E. canis as soon as 8h post application as demonstrated by E. canis DNA found in the nutritive blood medium. In conclusion, transmission of E. canis by R. sanguineus ticks starts within a few hours after attachment, which is earlier than previously thought. These findings underpin the need for acaricides to provide either a repellent, an anti-attachment and/or a rapid killing effect against ticks in order to decrease the risk of transmission of E. canis.
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transmission of ehrlichia canis by rhipicephalus sanguineus ticks feeding on dogs and on Artificial Membranes
Veterinary Parasitology, 2013Co-Authors: Josephus J Fourie, Dorothee Stanneck, Herman G Luus, Frederic Beugnet, Michiel Wijnveld, Frans JongejanAbstract:Abstract A South African strain of Ehrlichia canis was isolated and used to infect a laboratory-bred Beagle dog. Rhipicephalus sanguineus nymphs, which fed on this dog, moulted to adult ticks which carried infection rates of E. canis between 12% and 19% and were used in a series of in vivo and in vitro experiments. Five groups of 6 dogs were challenged with the infected R. sanguineus ticks, which were removed 24 h, 12 h, 6 h or 3 h after the ticks had been released onto the dogs. The animals were monitored for fever and thrombocytopenia and were considered infected if they became serologically positive for E. canis antibodies as well as PCR positive for E. canis DNA. Seven dogs became infected with E. canis in the following groups: Group 1 (24 h tick challenge) 1 out of 6; Group 2 (12 h) 1 of 6; Group 3 (6 h) 2 of 6; Group 4 (6 h) 2 of 6 and Group 5 (3 h) 1 out of 6. Six of those 7 infected dogs developed fever and a significant thrombocytopenia. One dog did not show any symptoms, but seroconverted and was found PCR positive on several occasions. Five additional dogs were PCR positive on one test sample only but were not considered infected because they did not develop any specific E. canis antibodies. In vitro, R. sanguineus ticks attached and fed on bovine blood through silicone Membranes with attachment rates up to 72.5% after 24 h increasing to 84.2% at 72 h. The ticks transmitted E. canis as soon as 8 h post application as demonstrated by E. canis DNA found in the nutritive blood medium. In conclusion, transmission of E. canis by R. sanguineus ticks starts within a few hours after attachment, which is earlier than previously thought. These findings underpin the need for acaricides to provide either a repellent, an anti-attachment and/or a rapid killing effect against ticks in order to decrease the risk of transmission of E. canis.
Charles Pidgeon - One of the best experts on this subject based on the ideXlab platform.
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immobilized Artificial Membranes screens for drug membrane interactions
Advanced Drug Delivery Reviews, 1997Co-Authors: Cheng Y Yang, Hanlan Liu, Song J Cai, Charles PidgeonAbstract:Abstract Immobilized Artificial Membranes (IAMs) are monolayers of phospholipid analogs covalently bonded to the surface of silica particles. 31P NMR and molecular dynamics (MD) simulations demonstrated that IAMs and liposome Membranes exhibit similar interfacial properties. These similar interfacial properties have resulted in IAMs' being useful as a physico-chemical model of drug-membrane partitioning. IAM chromatography has been successful used to predict: (1) solute partitioning into liposome Membranes; (2) drug permeability through Caco-2 cells; (3) drug intestinal absorption; (4) brain uptake of amino acids; (5) bile salt-membrane interactions; and (6) human skin permeability of steroids and alcohols. In addition, IAM chromatography has also been used to obtain hydrophobicity parameters for SAR studies.
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immobilized Artificial membrane chromatography measurements of membrane partition coefficient and predicting drug membrane permeability
Journal of Chromatography A, 1996Co-Authors: Shaowei Ong, Hanlan Liu, Charles PidgeonAbstract:Immobilized Artificial Membranes (IAMs) are chromatographic surfaces prepared by covalently immobilizing cell membrane phospholipids to solid surfaces at monolayer densities. IAM surfaces mimic fluid cell Membranes. For 23 structurally unrelated compounds, solute capacity factors [log (k'IAM)] measured on IAM columns correlate very well with the solute equilibrium partition coefficients [log (Km)] measured in fluid liposome systems (r = 0.907). This indicates that solute partitioning between the IAM bonded phase and the aqueous mobile phase is similar to the solute partitioning between liposomes and the aqueous phase. IAMs also predicted oral drug absorption in mice and drug permeability through Caco-2 cells. IAM chromatography is experimentally simple and large volume screening of experimental compounds for drug absorption is possible. Solute retention on IAMs was found to be dominated by a partitioning mechanism. The structural requirements for HPLC bonded phases to predict solute-membrane partitioning are briefly discussed.
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immobilized Artificial membrane chromatography measurements of membrane partition coefficient and predicting drug membrane permeability
Journal of Chromatography A, 1996Co-Authors: Charles PidgeonAbstract:Abstract Immobilized Artificial Membranes (IAMs) are chromatographic surfaces prepared by covalently immobilizing cell membrane phospholipids to solid surfaces at monolayer densities. IAM surfaces mimic fluid cell Membranes. For 23 structurally unrelated compounds, solute capacity factors [log (k′IAM)] measured on IAM columns correlate very well with the solute equilibrium partition coefficients [log (Km)] measured in fluid liposome systems (r = 0.907). This indicates that solute partitioning between the IAM bonded phase and the aqueous mobile phase is similar to the solute partitioning between liposomes and the aqueous phase. IAMs also predicted oral drug absorption in mice and drug permeability through Caco-2 cells. IAM chromatography is experimentally simple and large volume screening of experimental compounds for drug absorption is possible. Solute retention on IAMs was found to be dominated by a partitioning mechanism. The structural requirements for HPLC bonded to predict solute-membrane partitioning are briefly discussed.
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iam chromatography an in vitro screen for predicting drug membrane permeability
Journal of Medicinal Chemistry, 1995Co-Authors: Charles Pidgeon, Shaowei Ong, Hanlan Liu, X Qiu, M Pidgeon, A H Dantzig, J Munroe, W J Hornback, J S Kasher, L GlunzAbstract:Fluid cell Membranes are the main barrier to drug absorption when diffusion limits uptake. Immobilized Artificial Membranes (IAMs) are solid phase models of fluid Membranes that predicted oral drug absorption in mice for a homologous set of cephalosporins. IAMs also predicted drug permeability through Caco-2 cells. Since drug permeability in Caco-2 cells is known to correlate with the oral absorption of drugs in humans, IAMs may also model drug absorption in humans. IAM analysis is experimentally simple, and large-volume screening of experimental compounds for drug absorption is possible.
Hanlan Liu - One of the best experts on this subject based on the ideXlab platform.
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immobilized Artificial Membranes screens for drug membrane interactions
Advanced Drug Delivery Reviews, 1997Co-Authors: Cheng Y Yang, Hanlan Liu, Song J Cai, Charles PidgeonAbstract:Abstract Immobilized Artificial Membranes (IAMs) are monolayers of phospholipid analogs covalently bonded to the surface of silica particles. 31P NMR and molecular dynamics (MD) simulations demonstrated that IAMs and liposome Membranes exhibit similar interfacial properties. These similar interfacial properties have resulted in IAMs' being useful as a physico-chemical model of drug-membrane partitioning. IAM chromatography has been successful used to predict: (1) solute partitioning into liposome Membranes; (2) drug permeability through Caco-2 cells; (3) drug intestinal absorption; (4) brain uptake of amino acids; (5) bile salt-membrane interactions; and (6) human skin permeability of steroids and alcohols. In addition, IAM chromatography has also been used to obtain hydrophobicity parameters for SAR studies.
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immobilized Artificial membrane chromatography measurements of membrane partition coefficient and predicting drug membrane permeability
Journal of Chromatography A, 1996Co-Authors: Shaowei Ong, Hanlan Liu, Charles PidgeonAbstract:Immobilized Artificial Membranes (IAMs) are chromatographic surfaces prepared by covalently immobilizing cell membrane phospholipids to solid surfaces at monolayer densities. IAM surfaces mimic fluid cell Membranes. For 23 structurally unrelated compounds, solute capacity factors [log (k'IAM)] measured on IAM columns correlate very well with the solute equilibrium partition coefficients [log (Km)] measured in fluid liposome systems (r = 0.907). This indicates that solute partitioning between the IAM bonded phase and the aqueous mobile phase is similar to the solute partitioning between liposomes and the aqueous phase. IAMs also predicted oral drug absorption in mice and drug permeability through Caco-2 cells. IAM chromatography is experimentally simple and large volume screening of experimental compounds for drug absorption is possible. Solute retention on IAMs was found to be dominated by a partitioning mechanism. The structural requirements for HPLC bonded phases to predict solute-membrane partitioning are briefly discussed.
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iam chromatography an in vitro screen for predicting drug membrane permeability
Journal of Medicinal Chemistry, 1995Co-Authors: Charles Pidgeon, Shaowei Ong, Hanlan Liu, X Qiu, M Pidgeon, A H Dantzig, J Munroe, W J Hornback, J S Kasher, L GlunzAbstract:Fluid cell Membranes are the main barrier to drug absorption when diffusion limits uptake. Immobilized Artificial Membranes (IAMs) are solid phase models of fluid Membranes that predicted oral drug absorption in mice for a homologous set of cephalosporins. IAMs also predicted drug permeability through Caco-2 cells. Since drug permeability in Caco-2 cells is known to correlate with the oral absorption of drugs in humans, IAMs may also model drug absorption in humans. IAM analysis is experimentally simple, and large-volume screening of experimental compounds for drug absorption is possible.
