pharmacokinetic Articles
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A model to resolve the dynamics of organochlorine pharmacokinetics in migrating humpback whales
Humpback whales are iconic mammals at the top of the Antarctic food chain. Their large reserves of lipid rich tissues such as blubber predispose them to accumulation of lipophilic contaminants throughout their lifetime. Changes in the volumes and distribution of lipids in humpback whales, particularly during migration, could play an important role in the pharmacokinetics of lipophilic ...
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CYP‐mediated warfarin metabolic ability is not a critical determinant of warfarin sensitivity in avian species; in vitro assays in several birds and in vivo assays in chicken
Coumarin derivative anticoagulant rodenticides used for rodent control are posing a serious risk to wild bird populations. For warfarin (WF) a classic coumarin derivative, chicken have a high LD50 while mammalian species generally have much lower LD50. Large interspecies differences in sensitivity to WF are to be expected. We previously reported substantial differences in WF metabolism among ...
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New levodopa therapeutic strategies
Abstract During its almost half-century of use for treating Parkinson's disease, levodopa therapy has permitted most patients to reverse much of this disorder's symptomatology. However, the full range of its therapeutic properties is not completely understood, as levodopa is showing itself to be more than just a metabolic intermediate for dopamine synthesis. Improving the constancy of drug ...
By Sensidose AB
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A physiologically‐based pharmacokinetic model for disposition of 2,3,7,8‐TCDD in fathead minnow and medaka
A Physiologically‐Based Pharmacokinetic (PBPK) model was developed for the disposition of 2,3,7,8‐TCDD in two fish species, fathead minnow and medaka. The model was developed based on the empirical data on disposition of dioxins in fish tissues, as well as existing knowledge on the mechanisms of uptake, distribution, storage and elimination of dioxins in various species (other than fish). This ...
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First-in-Human Dose Finding Study of Venadaparib (IDX-1197), a Potent and Selective PARP inhibitor, in Patients with Advanced Solid Tumors
Poly ADP-ribose polymerase (PARP) is an enzyme that is central to the repair of DNA replication errors known as single-strand breaks. PARP inhibitors are currently approved (or ovary, breast, pancreatic and prostate cancers which harbor BRCA1/2 mutations and/or homologous recombinant repair mutation. In this phase 1 dose escalation study of venadaparib, we determined the maximum tolerated dose ...
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ADCs Customized Linkers
Antibody Drug Conjugates (ADCs) use targeting ability of monoclonal antibodies to deliver potent cytototoxic payloads to their intended target. The linker encompasses a conjugating functionality suitable for attachment to the antibody, a spacer unit that typically incorporates a hydrophilic element and a trigger which releases the potent cytototoxic warhead. The properties that an optimal linker ...
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Nanodrug potential in cancer therapy: efficacy/toxicity studies in cancer cells
The interest of nanotechnology to find a more effective approach for drug delivery is growing fast. Nanoparticles as drug vehicles potentially improve the pharmacokinetic and pharmacodynamic properties of various types of drugs, and provide a tool to visualise molecules and tumour target cells that otherwise cannot be detected through conventional imaging. However, there are many aspects of ...
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Methylmercury accumulation and elimination in mink (Neovison vison) hair and blood: Results of a controlled feeding experiment using stable isotope tracers
Concentrations of metals in hair are used often to develop pharmacokinetic models for both animals and humans. While data on uptake are available, elimination kinetics are less well understood; stable isotope tracers provide an excellent tool for measuring uptake and elimination kinetics. In the present study, methylmercury (MeHg) concentrations through time were measured in the hair and blood ...
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Augmentation of anti–tumour activity of cisplatin by pectin nano–conjugates in B–16 mouse model: pharmacokinetics and in–vivo biodistribution of radio–labelled, hydrophilic nano–conjugates
Nanoconjugates have matured from simple devices to multifunctional, biodegradable, non–toxic and non–immunogenic constructs, capable of delivering synergistically functioning drugs in vivo. The present study evaluates the efficacy of drug polymer self folding nano–conjugates of pectin–cisplatin to enhance blood circulating levels of cisplatin. Physical characterisation was done by DLS, zeta ...
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Abstract 10306: Identification and Characterization of Orally Bioavailable Small Molecule Protease Proprotein Convertase Subtilisin-like Kexin Type 9 Inhibitors (Best of Basic Science Abstract)
Abstract Intervention with drugs to reduce low density lipoprotein-cholesterol (LDL-C) has proven to decrease mortality and morbidity. Here, we report the development of small molecules that lower LDL-C by targeting the LDL-receptor (LDLR) degradation pathway, which is modulated by the protease proprotein convertase subtilisin-like kexin type 9 (PCSK9). PCSK9 is synthesized as a 72-kDa zymogen ...
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Glycosylation of Fc Fusion Proteins: Insights into its Biological Significance
Fc fusion protein (Fc-Fusion) has a complex and diverse molecular structure, and may contain glycosylation modification sites at amino acid 297 of its Fc fragment and the Fab region of some molecules. Moreover, its biological ligands are structurally diverse, and their glycosylation modifications may also be complex, usually involving multiple N-glycan and O-glycan sites and a large number of ...
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Understanding the Importance of Preclinical Animal Models in Drug Development
In the world of pharmaceuticals, developing safe and effective drugs is a complex and time-consuming process. Before a new drug candidate can progress to clinical trials and ultimately reach the market, it needs to undergo rigorous testing in various model systems to assess its efficacy and safety. One critical component of this evaluation is the use of preclinical animal models. Preclinical ...
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How to Apply In Vitro DMPK Services to Support Drug Development and ADMET Study
Drug development is a complex and multifaceted process that involves extensive research and testing to ensure safety, efficacy and quality for human use. One critical element in the drug development process is drug metabolism and pharmacokinetics (DMPK), which refers to how a drug is absorbed, distributed, metabolized, and excreted (ADME) from the body. In vitro DMPK services, along with ...
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How to Apply In Vitro DMPK Services to Support Drug Development and ADMET Study
Drug development is a complex and multifaceted process that involves extensive research and testing to ensure safety, efficacy and quality for human use. One critical element in the drug development process is drug metabolism and pharmacokinetics (DMPK), which refers to how a drug is absorbed, distributed, metabolized, and excreted (ADME) from the body. In vitro DMPK services, along with ...
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Synthesis and characterisation of new designed protoporphyrin-stabilised gold nanoparticles for cancer cells nanotechnology-based targeting
Nanotechnology has entered the field of medicine in recent dacades and especially, in drug delivery systems, nanoparticles have shown an ability to improve pharmacokinetics, pharmacodynamics, efficacy and to reduce the toxicity of associated drugs. In this study, we have designed a new protoporphyrin-conjugated gold nanoparticle to selectively target and photo- or sonodynamic therapy of tumoural ...
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Bioconjugation Strategies for Enhancing Drug Delivery and Therapeutic Efficacy
In recent years, bioconjugation has emerged as a powerful strategy for improving drug delivery and enhancing therapeutic efficacy. By linking drugs to various biological entities, such as proteins, antibodies, nanoparticles, or targeting moieties, bioconjugation enables precise and targeted delivery of therapeutic agents to desired sites. This article aims to provide an overview of different ...
By BOC Sciences
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121 - Development of Protease Proprotein Convertase Subtilisin-Like Kexin Type 9 Antagonists
Abstract Protease proprotein convertase subtilisin-like kexin type 9 (PCSK9) is an important target for the treatment of hypercholesterolemia. Several pharmaceutical companies have focused on the development of mAbs. Yet, our approach has focused on developing orally bioavailable small molecule antagonists. PCSK9 is a serine protease that is synthesized as a zymogen that undergoes autocatalytic ...
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The Function of Drug Coating
Coating refers to the unit operation of applying a layer of outer coating material to the dry surface of the formulation. This coating material not only makes the product easier to identify, but even improves the pharmacokinetic properties of the drug by altering its release: ensuring that the drug reaches its target and provides sufficient concentrations in the body to be maintained for an ...
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Huateng Pharma Supplies Ensitrelvir Intermeidates Against COVID-19
Ensitrelvir (code name S-217622, brand name Xocova), is a new inhibitor of the SARS-CoV-2 major protease (Mpro), also known as 3C-like protease, has been shown to reduce the viral load and help alleviate the severity of SARS-CoV-2 in infected hamsters. In cells, low nanomolar to sub-micromolar doses of Ensitrelvir suppress viral growth. In hamsters, oral treatment of Ensitrelvir showed excellent ...
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Medication Adherence Data Used Proactively in Clinical Trials
From clinical trial enrollment through completion, understanding medication adherence is critical to data integrity and AiCure offers a competitive edge where traditional methods fall short. To ensure trial participants are complying with dosing regimens, sites often rely on traditional patient reported outcome systems with participant diaries, which can be unreliable. Also in common use are ...
By AiCure
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