The Experts below are selected from a list of 42 Experts worldwide ranked by ideXlab platform
Stephen Toovey - One of the best experts on this subject based on the ideXlab platform.
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tafenoquine and primaquine do not exhibit clinical neurologic signs associated with central nervous system lesions in the same manner as earlier 8 aminoquinolines
Malaria Journal, 2018Co-Authors: Judith Berman, Geoffrey S. Dow, Tracey Brown, Stephen TooveyAbstract:Tafenoquine was recently approved for Plasmodium vivax radical cure (KRINTAFEL™) and malaria prevention (ARAKODA™). A review of the non-clinical and clinical literature was conducted to assess whether tafenoquine (and primaquine) exhibit the same neurologic lesions and associated clinical signs as earlier 8-aminoquinolines, as has been alleged in recent opinion pieces. Plasmocid, Pamaquine and pentaquine damage specific neuro-anatomical structures in Rhesus monkeys and humans leading to corresponding deficits in neurologic function. Neurologic therapeutic indices for these 3 drugs calculated based on monkey data were well correlated with human data. Despite 60 years of use, there is no evidence that primaquine exhibits similar neurotoxicity in humans. Extrapolation of data from Rhesus monkeys to humans, and the available clinical data, suggest that tafenoquine also does not exhibit Pamaquine, pentaquine or plasmocid-like clinical neurologic signs in humans.
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Tafenoquine and primaquine do not exhibit clinical neurologic signs associated with central nervous system lesions in the same manner as earlier 8-aminoquinolines
Malaria Journal, 2018Co-Authors: Jonathan Berman, Tracey Brown, Geoffrey Dow, Stephen TooveyAbstract:Background Tafenoquine was recently approved for Plasmodium vivax radical cure (KRINTAFEL™) and malaria prevention (ARAKODA™). Methods A review of the non-clinical and clinical literature was conducted to assess whether tafenoquine (and primaquine) exhibit the same neurologic lesions and associated clinical signs as earlier 8-aminoquinolines, as has been alleged in recent opinion pieces. Results Plasmocid, Pamaquine and pentaquine damage specific neuro-anatomical structures in Rhesus monkeys and humans leading to corresponding deficits in neurologic function. Neurologic therapeutic indices for these 3 drugs calculated based on monkey data were well correlated with human data. Despite 60 years of use, there is no evidence that primaquine exhibits similar neurotoxicity in humans. Discussion/conclusions Extrapolation of data from Rhesus monkeys to humans, and the available clinical data, suggest that tafenoquine also does not exhibit Pamaquine, pentaquine or plasmocid-like clinical neurologic signs in humans.
Colin Ohrt - One of the best experts on this subject based on the ideXlab platform.
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An In vivo Drug Screening Model Using Glucose-6-Phosphate Dehydrogenase Deficient Mice to Predict the Hemolytic Toxicity of 8-Aminoquinolines
2016Co-Authors: Peng Zhang, Xiugong Gao, Hiroshi Ishida, Jack Amnuaysirikul, Peter J. Weina, Max Grogl, Michael T. O’neil, Diana Caridha, Colin OhrtAbstract:Abstract. Anti-malarial 8-aminoquinolines drugs cause acute hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDD). Efforts to develop non-hemolytic 8-aminoquinolines have been severely limited caused by the lack of a predictive in vivo animal model of hemolytic potential that would allow screening of candidate compounds. This report describes a G6PDD mouse model with a phenotype closely resembling the G6PDD phenotype found in the African A-type G6PDD human. These G6PDD mice, given different doses of primaquine, which used as a reference hemolytic drug, display a full array of hemolytic anemia parameters, consistently and reproducibly. The hemolytic and therapeutic indexes were generated for evaluation of hemotoxicity of drugs. This model demonstrated a complete hemolytic toxicity response to another known hemolytic antimalarial drug, Pamaquine, but no response to non-hemolytic drugs, chloroquine and mefloquine. These results suggest that this model is suitable for evaluation of selected 8-AQ type candidate antimalarial drugs for their hemolytic potential
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ZHANG AND OTHERS 8-AMINOQUINOLINES HEMOLYTIC TOXICITY IN G6PD-DEFICIENT MICE An In vivo Drug Screening Model Using Glucose-6-Phosphate Dehydrogenase Deficient Mice to Predict the Hemolytic Toxicity of 8-Aminoquinolines
2016Co-Authors: Peng Zhang, Colin Ohrt, Xiugong Gao, Hiroshi Ishida, Jack Amnuaysirikul, Peter J. Weina, Max Grogl, Diana Caridha, Mark HickmanAbstract:Anti-malarial 8-aminoquinolines drugs cause acute hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDD). Efforts to develop non-hemolytic 8-aminoquinolines have been severely limited caused by the lack of a predictive in vivo animal model of hemolytic potential that would allow screening of candidate compounds. This report describes a G6PDD mouse model with a phenotype closely resembling the G6PDD phenotype found in the African A-type G6PDD human. These G6PDD mice, given different doses of primaquine, which used as a reference hemolytic drug, display a full array of hemolytic anemia parameters, consistently and reproducibly. The hemolytic and therapeutic indexes were generated for evaluation of hemotoxicity of drugs. This model demonstrated a complete hemolytic toxicity response to another known hemolytic antimalarial drug, Pamaquine, but no response to non-hemolytic drugs, chloroquine and mefloquine. These results suggest that this model is suitable for evaluation of selected 8-AQ type candidate antimalarial drugs for their hemolytic potential
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humanized mouse model of glucose 6 phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Rosemary Rochford, Colin Ohrt, Paul C Baresel, Brice Campo, Aruna Sampath, Alan J Magill, Babu L Tekwani, Larry A WalkerAbstract:Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk for the development of hemolytic anemia when given 8-aminoquinolines (8-AQs), an important class of antimalarial/antiinfective therapeutics. However, there is no suitable animal model that can predict the clinical hemolytic potential of drugs. We developed and validated a human (hu)RBC-SCID mouse model by giving nonobese diabetic/SCID mice daily transfusions of huRBCs from G6PD-deficient donors. Treatment of SCID mice engrafted with G6PD-deficient huRBCs with primaquine, an 8-AQ, resulted in a dose-dependent selective loss of huRBCs. To validate the specificity of this model, we tested known nonhemolytic antimalarial drugs: mefloquine, chloroquine, doxycycline, and pyrimethamine. No significant loss of G6PD-deficient huRBCs was observed. Treatment with drugs known to cause hemolytic toxicity (Pamaquine, sitamaquine, tafenoquine, and dapsone) resulted in loss of G6PD-deficient huRBCs comparable to primaquine. This mouse model provides an important tool to test drugs for their potential to cause hemolytic toxicity in G6PD-deficient populations.
Larry A Walker - One of the best experts on this subject based on the ideXlab platform.
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humanized mouse model of glucose 6 phosphate dehydrogenase deficiency for in vivo assessment of hemolytic toxicity
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Rosemary Rochford, Colin Ohrt, Paul C Baresel, Brice Campo, Aruna Sampath, Alan J Magill, Babu L Tekwani, Larry A WalkerAbstract:Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk for the development of hemolytic anemia when given 8-aminoquinolines (8-AQs), an important class of antimalarial/antiinfective therapeutics. However, there is no suitable animal model that can predict the clinical hemolytic potential of drugs. We developed and validated a human (hu)RBC-SCID mouse model by giving nonobese diabetic/SCID mice daily transfusions of huRBCs from G6PD-deficient donors. Treatment of SCID mice engrafted with G6PD-deficient huRBCs with primaquine, an 8-AQ, resulted in a dose-dependent selective loss of huRBCs. To validate the specificity of this model, we tested known nonhemolytic antimalarial drugs: mefloquine, chloroquine, doxycycline, and pyrimethamine. No significant loss of G6PD-deficient huRBCs was observed. Treatment with drugs known to cause hemolytic toxicity (Pamaquine, sitamaquine, tafenoquine, and dapsone) resulted in loss of G6PD-deficient huRBCs comparable to primaquine. This mouse model provides an important tool to test drugs for their potential to cause hemolytic toxicity in G6PD-deficient populations.
Tracey Brown - One of the best experts on this subject based on the ideXlab platform.
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tafenoquine and primaquine do not exhibit clinical neurologic signs associated with central nervous system lesions in the same manner as earlier 8 aminoquinolines
Malaria Journal, 2018Co-Authors: Judith Berman, Geoffrey S. Dow, Tracey Brown, Stephen TooveyAbstract:Tafenoquine was recently approved for Plasmodium vivax radical cure (KRINTAFEL™) and malaria prevention (ARAKODA™). A review of the non-clinical and clinical literature was conducted to assess whether tafenoquine (and primaquine) exhibit the same neurologic lesions and associated clinical signs as earlier 8-aminoquinolines, as has been alleged in recent opinion pieces. Plasmocid, Pamaquine and pentaquine damage specific neuro-anatomical structures in Rhesus monkeys and humans leading to corresponding deficits in neurologic function. Neurologic therapeutic indices for these 3 drugs calculated based on monkey data were well correlated with human data. Despite 60 years of use, there is no evidence that primaquine exhibits similar neurotoxicity in humans. Extrapolation of data from Rhesus monkeys to humans, and the available clinical data, suggest that tafenoquine also does not exhibit Pamaquine, pentaquine or plasmocid-like clinical neurologic signs in humans.
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Tafenoquine and primaquine do not exhibit clinical neurologic signs associated with central nervous system lesions in the same manner as earlier 8-aminoquinolines
Malaria Journal, 2018Co-Authors: Jonathan Berman, Tracey Brown, Geoffrey Dow, Stephen TooveyAbstract:Background Tafenoquine was recently approved for Plasmodium vivax radical cure (KRINTAFEL™) and malaria prevention (ARAKODA™). Methods A review of the non-clinical and clinical literature was conducted to assess whether tafenoquine (and primaquine) exhibit the same neurologic lesions and associated clinical signs as earlier 8-aminoquinolines, as has been alleged in recent opinion pieces. Results Plasmocid, Pamaquine and pentaquine damage specific neuro-anatomical structures in Rhesus monkeys and humans leading to corresponding deficits in neurologic function. Neurologic therapeutic indices for these 3 drugs calculated based on monkey data were well correlated with human data. Despite 60 years of use, there is no evidence that primaquine exhibits similar neurotoxicity in humans. Discussion/conclusions Extrapolation of data from Rhesus monkeys to humans, and the available clinical data, suggest that tafenoquine also does not exhibit Pamaquine, pentaquine or plasmocid-like clinical neurologic signs in humans.
Judith Berman - One of the best experts on this subject based on the ideXlab platform.
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tafenoquine and primaquine do not exhibit clinical neurologic signs associated with central nervous system lesions in the same manner as earlier 8 aminoquinolines
Malaria Journal, 2018Co-Authors: Judith Berman, Geoffrey S. Dow, Tracey Brown, Stephen TooveyAbstract:Tafenoquine was recently approved for Plasmodium vivax radical cure (KRINTAFEL™) and malaria prevention (ARAKODA™). A review of the non-clinical and clinical literature was conducted to assess whether tafenoquine (and primaquine) exhibit the same neurologic lesions and associated clinical signs as earlier 8-aminoquinolines, as has been alleged in recent opinion pieces. Plasmocid, Pamaquine and pentaquine damage specific neuro-anatomical structures in Rhesus monkeys and humans leading to corresponding deficits in neurologic function. Neurologic therapeutic indices for these 3 drugs calculated based on monkey data were well correlated with human data. Despite 60 years of use, there is no evidence that primaquine exhibits similar neurotoxicity in humans. Extrapolation of data from Rhesus monkeys to humans, and the available clinical data, suggest that tafenoquine also does not exhibit Pamaquine, pentaquine or plasmocid-like clinical neurologic signs in humans.
