A5055732602- Malaria Research and Control
- Drug Transport and Resistance Mechanisms
- Pharmacogenetics and Drug Metabolism
- Drug-Induced Hepatotoxicity and Protection
- Computational Drug Discovery Methods
- HIV/AIDS drug development and treatment
- Mosquito-borne diseases and control
- Pharmacological Effects and Toxicity Studies
- Synthesis and biological activity
- Research on Leishmaniasis Studies
- Hemoglobinopathies and Related Disorders
- Pharmacological Effects of Natural Compounds
- Antibiotics Pharmacokinetics and Efficacy
- Estrogen and related hormone effects
- Multiple Myeloma Research and Treatments
- Neonatal Health and Biochemistry
- Genomics and Phylogenetic Studies
- Eicosanoids and Hypertension Pharmacology
- Synthesis and Catalytic Reactions
- Infectious Encephalopathies and Encephalitis
- Drug Solubulity and Delivery Systems
- Endometriosis Research and Treatment
- Pharmacological Effects and Assays
- Rabbits: Nutrition, Reproduction, Health
- Metabolomics and Mass Spectrometry Studies
Shandong Agricultural University
2021-2023
China University of Petroleum, East China
2021-2022
Walter Reed Army Institute of Research
2011-2021
Sichuan Agricultural University
2021
Uniformed Services University of the Health Sciences
2009
Mahidol University
2004
Tongji University
1990
Huazhong University of Science and Technology
1987
The efficacy of the 8-aminoquinoline (8AQ) drug primaquine (PQ) has been historically linked to CYP-mediated metabolism. Although date no clear evidence exists in literature that unambiguously assigns metabolic pathway or specific metabolites necessary for activity, recent suggests a role CYP 2D6 generation redox active metabolites. In present study, inhibitor paroxetine was used assess its effects on production phenolic thought be involved PQ efficacy. Further, causal prophylactic...
Tafenoquine (TQ) is an 8-aminoquinoline (8AQ) that has been tested in several Phase II and III clinical studies currently late stage development as anti-malarial prophylactic agent. NPC-1161B a promising 8AQ preclinical development. It recently reported the drug primaquine requires metabolic activation by CYP 2D6 for efficacy humans mice, highlighting importance of pharmacogenomics target population when administering primaquine. A logical follow-up study was to determine whether 2D required...
Primaquine (PQ) metabolism by the cytochrome P450 (CYP) 2D family of enzymes is required for antimalarial activity in both humans (2D6) and mice (2D). Human CYP 2D6 highly polymorphic, decreased enzyme has been linked to PQ activity. Despite importance efficacy, exact role that these play pharmacokinetics not extensively studied vivo. In this study, a series pharmacokinetic experiments were conducted with differential characteristics, including wild-type (WT), knockout (KO), humanized...
ABSTRACT The antimalarial activity and pharmacology of a series phenylthiazolyl-bearing hydroxamate-based histone deacetylase inhibitors (HDACIs) was evaluated. In in vitro growth inhibition assays approximately 50 analogs were evaluated against four drug resistant strains Plasmodium falciparum . range 50% inhibitory concentrations (IC s) 0.0005 to >1 μM. Five exhibited IC s <3 nM, three these selectivity indices >600. most potent compound, WR301801 (YC-2-88) shown cause...
As anti-malarial drug resistance escalates, new safe and effective medications are necessary to prevent treat malaria infections. The US Army is developing tafenoquine (TQ), an analogue of primaquine (PQ), which expected be more in preventing deployed military personnel. To compare the prophylactic efficacy TQ PQ, a transgenic Plasmodium berghei parasite expressing bioluminescent reporter protein luciferase was utilized visualize quantify development C57BL/6 albino mice treated with PQ...
ELQ-300 is a preclinical antimalarial drug candidate that active against liver, blood, and transmission stages of Plasmodium falciparum. While highly effective when administered in low multidose regimen, poor aqueous solubility high crystallinity have hindered its clinical development. To overcome challenging physiochemical properties, number bioreversible alkoxycarbonate ester prodrugs were synthesized. These are converted to by host parasite esterase action the liver bloodstream host. One...
The need for improved malaria diagnostics has long been recognized.Human parasitized erythrocytes based on the principles of flow cytometry (FCM) method is described determination parasitemia in Plasmodium falciparum cultures using fluorescence activated cell sorter and DNA-binding fluorescent dye, YOYO-1. same assay samples can be also evaluated both microscopically by scintillation counting after use (3)H-hypoxanthine-labeled parasites.The counts uninfected, infected, nucleated cells...
ABSTRACT Cytochrome P450 (CYP) 2D metabolism is required for the liver-stage antimalarial efficacy of 8-aminoquinoline molecule tafenoquine in mice. This could be problematic Plasmodium vivax radical cure, as human CYP ortholog (2D6) highly polymorphic. Diminished 2D6 enzyme activity, poor-metabolizer phenotype, compromise curative humans. Despite importance efficacy, exact role that plays and pharmacokinetics other molecules has not been extensively studied. In this study, a series...
SUMMARY Maize is an important crop worldwide, as well a valuable model with vast genetic diversity. Accurate genome and annotation information for wide range of inbred lines would provide resources improvement pan‐genome characterization. In this study, we generated high‐quality de novo assembly (contig N50 15.43 Mb) the Chinese elite line RP125 using Nanopore long‐read sequencing Hi‐C scaffolding, which yield highly contiguous, chromosome‐length scaffolds. Global comparison those B73, W22,...
The present study reports the tissue distribution, pharmacokinetics, mass balance, and elimination of [(14)C] artesunate (AS) following single intravenous administration in rats. Protein binding was performed with rat human plasma. Radioactivity drug levels blood, plasma, tissues, urine, feces up to 192 hours were collected measured. mean terminal half-life plasma (76 h) blood (105 radioactivity prolonged compared that unchanged AS (0.43 dihydroartemisinin (0.75 h), an active metabolite AS....
Abstract Background Dihydroartemisinin (DHA), a powerful anti-malarial drug, has been used as monotherapy and artemisinin-based combination therapy (ACT) for more than decades. So far, however, the tissue distribution metabolic profile of DHA data are not available from animal humans. Methods Pharmacokinetics, distribution, mass balance, elimination [ 14 C] have studieded in rats following single intravenous administration. Protein binding was performed with rat human plasma. Drug...
The pharmacokinetics of good manufacturing process injection artesunate (AS) were evaluated after single doses at 0.5, 1, 2, 4, and 8 mg/kg with a 2-minute infusion in 40 healthy subjects. Drug concentrations analyzed by validated liquid chromatography mass spectrometry system (LC-MS/MS) procedures. drug was immediately converted to dihydroartemisinin (DHA), elimination half-lives ranging 0.12–0.24 1.15–2.37 hours for AS DHA, respectively. Pharmacokinetic model-dependent analysis is suitable...
Severe malaria results in over a million deaths every year, most of them children aged less than five years and living sub-Saharan Africa. Injectable artesunate (AS) was recommended as initial treatment for severe by WHO 2006. The Walter Reed Army Institute Research (WRAIR) has been developing novel good manufacturing practice (GMP) injection AS, which approved the US FDA investigational drug use distribution CDC.Tolerability pharmacokinetics current GMP intravenous an anti-malarial agent,...
Plasmodium vivax malaria requires a 2-week course of primaquine (PQ) for radical cure. Evidence suggests that the hepatic isoenzyme cytochrome P450 2D6 (CYP2D6) is key enzyme required to convert PQ into its active metabolite.CYP2D6 genotypes and phenotypes 550 service personnel were determined, pharmacokinetics (PK) 30-mg oral dose was measured in 45 volunteers. Blood urine samples collected, with metabolites using ultraperformance liquid chromatography mass spectrometry.Seventy-six CYP2D6...
Apicomplexan infections cause substantial morbidity and mortality, worldwide. New, improved therapies are needed. Herein, we create a next generation anti-apicomplexan lead compound, JAG21, tetrahydroquinolone, with increased sp3-character to improve parasite selectivity. Relative other cytochromeb inhibitors, JAG21 has solubility ADMET properties, without need for pro-drug. significantly reduces Toxoplasma gondii tachyzoites encysted bradyzoites in vitro, primary established chronic vivo....
Decoquinate (DQ) is highly effective at killing malaria parasites in vitro ; however, it extremely insoluble water. In this study, solid dispersion method was used for DQ formulation which created a suitable physical form of aqueous phase particle manipulation. Among many polymers and surfactants tested, polyvinylpyrrolidone 10, polymer, L- α -phosphatidylcholine or polysorbate, two surfactants, were chosen as components. The particles reduced to mean size between 200 400 nm, stable medium...
Comparative toxicokinetic (TK) and hydrolysis studies of intravenously administered two new antimalarial agents, artelinate (AL) artesunate (AS), were performed in malaria-infected rats using three daily equimolar doses (96 micromoles/kg). The TK evaluation was related to select one drug for severe malaria treatment U.S. Army. Drug concentration AS with dose 36.7 mg/kg one-third less on day 3 than 1, which resembled its active metabolite, dihydroartemisinin (DHA), suggesting an autoinduction...