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Marine Drugs Nov 2020Marine organisms represent an excellent source of innovative compounds that have the potential for the development of new drugs. The pharmacokinetics of marine drugs has... (Review)
Review
Marine organisms represent an excellent source of innovative compounds that have the potential for the development of new drugs. The pharmacokinetics of marine drugs has attracted increasing interest in recent decades due to its effective and potential contribution to the selection of rational dosage recommendations and the optimal use of the therapeutic arsenal. In general, pharmacokinetics studies how drugs change after administration via the processes of absorption, distribution, metabolism, and excretion (ADME). This review provides a summary of the pharmacokinetics studies of marine-derived active compounds, with a particular focus on their ADME. The pharmacokinetics of compounds derived from algae, crustaceans, sea cucumber, fungus, sea urchins, sponges, mollusks, tunicate, and bryozoan is discussed, and the pharmacokinetics data in human experiments are analyzed. In-depth characterization using pharmacokinetics is useful for obtaining information for understanding the molecular basis of pharmacological activity, for correct doses and treatment schemes selection, and for more effective drug application. Thus, an increase in pharmacokinetic research on marine-derived compounds is expected in the near future.
Topics: Animals; Aquatic Organisms; Biological Availability; Biological Products; Drug Dosage Calculations; Half-Life; Humans; Metabolic Clearance Rate; Tissue Distribution
PubMed: 33182407
DOI: 10.3390/md18110557 -
Journal of Medical Toxicology :... Apr 2019Cyanide, a metabolic poison, is a rising chemial threat and ingestion is the most common route of exposure. Terrorist organizations have threatened to attack the USA and... (Review)
Review
Cyanide, a metabolic poison, is a rising chemial threat and ingestion is the most common route of exposure. Terrorist organizations have threatened to attack the USA and international food and water supplies. The toxicokinetics and toxicodynamics of oral cyanide are unique, resulting in high-dose exposures, severe symptoms, and slower onset of symptoms. There are no FDA-approved therapies tested for oral cyanide ingestions and no approved intramuscular or oral therapies, which would be valuable in mass casualty settings. The aim of this review is to evaluate the risks of oral cyanide and its unique toxicokinetics, as well as address the lack of available rapid diagnostics and treatments for mass casualty events. We will also review current strategies for developing new therapies. A review of the literature using the PRISMA checklist detected 7284 articles, screened 1091, and included 59 articles or other reports. Articles referenced in this review were specific to risk, clinical presentation, diagnostics, current treatments, and developing therapies. Current diagnostics of cyanide exposure can take hours or days, which can delay treatment. Moreover, current therapies for cyanide poisoning are administered intravenously and are not specifically tested for oral exposures, which can result in higher cyanide doses and unique toxicodynamics. New therapies developed for oral cyanide exposures that are easily delivered, safe, and can be administered quickly by first responders in a mass casualty event are needed. Current research is aimed at identifying an antidote that is safe, effective, easy to administer, and has a rapid onset of action.
Topics: Administration, Oral; Antidotes; Cyanides; Humans; Mass Casualty Incidents; Poisoning; Risk; Terrorism; Toxicokinetics
PubMed: 30539383
DOI: 10.1007/s13181-018-0688-y -
Wiley Interdisciplinary Reviews.... Nov 2022The rapid growth of nanomaterial applications has raised safety concerns for human health. A number of studies have been conducted to assess the toxicokinetics,... (Review)
Review
The rapid growth of nanomaterial applications has raised safety concerns for human health. A number of studies have been conducted to assess the toxicokinetics, toxicology, dose-response, and risk assessment of different nanomaterials using in vitro and in vivo animal and human models. However, current studies cannot meet the demand for efficient assessment of toxicokinetics, dose-response relationships, or the toxicological risk arising from the rapidly increasing number of newly synthesized nanomaterials. In this article, we review the methods for conducting toxicokinetics, hazard identification, dose-response, exposure, and risk assessment studies of nanomaterials, identify the knowledge gaps, and discuss the challenges remaining. We provide the rationale behind the appropriate design of nanomaterial plasma toxicokinetic and tissue distribution studies, including caveats on the interpretation and correlation of in vitro and in vivo toxicology studies. The potential of using physiologically based pharmacokinetic (PBPK) models to extrapolate toxicokinetic and toxicity findings from in vitro to in vivo and from animals to humans is discussed, and the knowledge gaps of PBPK modeling for nanomaterials are identified. While challenges still exist, there has been progress in the toxicokinetics, hazard identification, and risk assessment of nanomaterials in the past two decades. Recent advancements in the field are highlighted with relevant examples. We also share latest guidelines as well as our perspectives on future studies needed to characterize the toxicokinetics, toxicity, and dose-response relationship in support of nanomaterial risk assessment. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.
Topics: Animals; Humans; Toxicokinetics; Risk Assessment; Nanostructures; Nanomedicine; Tissue Distribution
PubMed: 36416026
DOI: 10.1002/wnan.1808 -
Clinical and Translational Science Nov 2018The tutorial introduces the readers to the fundamentals of antibody pharmacokinetics (PK) in the context of drug development. Topics covered include an overview of...
The tutorial introduces the readers to the fundamentals of antibody pharmacokinetics (PK) in the context of drug development. Topics covered include an overview of antibody development, PK characteristics, and the application of antibody PK/pharmacodynamics (PD) in research and development decision-making. We also discuss the general considerations for planning a nonclinical PK program and describe the types of PK studies that should be performed during early development of monoclonal antibodies.
Topics: Antibodies, Monoclonal; Biological Availability; Clinical Trials as Topic; Decision Making; Drug Development; Half-Life; History, 21st Century; Humans; Metabolic Clearance Rate; Models, Biological; Molecular Targeted Therapy; Tissue Distribution
PubMed: 29877608
DOI: 10.1111/cts.12567 -
Drug Metabolism and Pharmacokinetics Feb 2018In the earliest stage of drug discovery/development, various cell-based models and animal models were used for the prediction of human pharmacokinetics and... (Review)
Review
In the earliest stage of drug discovery/development, various cell-based models and animal models were used for the prediction of human pharmacokinetics and toxicokinetics. Unfortunately, drugs under development are often discontinued because their nonclinical results do not extrapolate to human clinical studies in relation to either safety or efficacy. Therefore, it is important to improve the time- and cost-effectiveness of drug development. This might be achieved by developing new technologies including pharmacokinetics and toxicokinetics models that use human and mouse artificial chromosome vectors (HACs/MACs). HACs/MACs are unique vectors with several advantages: 1) independent maintenance, 2) defined copy number and mitotically stable, 3) no silencing of the transgene, and 4) no limitation of DNA insertion size. This review provides information on the advantages and examples of the utility of various models based on the recent advances in HAC/MAC technologies, including multifunctional cell-based models for assaying drug-drug interactions, bidirectional permeability, and cytotoxicity, as well as fully genetically humanized mouse models. We also discuss the future prospects of these technologies to advance drug discovery. In summary, these technologies offer advantages over current conventional models and should improve the success rate of drug development related to efficacy and safety for humans.
Topics: Animals; Chromosomes, Artificial; Chromosomes, Artificial, Human; Cloning, Molecular; Drug Discovery; Gene Transfer Techniques; Genetic Vectors; Humans; Mice; Toxicokinetics
PubMed: 29398301
DOI: 10.1016/j.dmpk.2018.01.002 -
Xenobiotica; the Fate of Foreign... Feb 2021We investigated the plasma toxicokinetic behavior of free (parent) and total (parent and conjugated forms) of bisphenol S (BPS) and bisphenol AF (BPAF) in plasma of...
We investigated the plasma toxicokinetic behavior of free (parent) and total (parent and conjugated forms) of bisphenol S (BPS) and bisphenol AF (BPAF) in plasma of adult male rats and mice following exposure via feed for 7 days to BPS (338, 1125, and 3375 ppm) or BPAF (338, 1125, and 3750 ppm). In rats, the exposure concentration-normalized maximum concentration [C/D (ng/mL)/(ppm)] and area under the concentration time curve [AUC/D (h × ng/mL)/(ppm)] for free was higher for BPS (C/D: 0.476-1.02; AUC/D: 3.58-8.26) than for BPAF (C/D: 0.017-0.037; AUC/D:0.196-0.436). In mice, the difference in systemic exposure parameters between free BPS (C/D: 0.376-0.459; AUC/D: 1.52-2.54) and free BPAF (C/D: 0.111-0.165; AUC/D:0.846-1.09) was marginal. Elimination half-lives for free analytes (4.41-10.4 h) were comparable between species and analogues. When systemic exposure to free analyte was compared between species, in rats, BPS exposure was slightly higher but BPAF exposure was much lower than in mice. BPS and BPAF were highly conjugated; total BPS AUC values (rats ≥18-fold, mice ≥17-fold) and BPAF (rats ≥127-fold, mice ≥16-fold) were higher than corresponding free values. Data demonstrated that there are analogue and species differences in the kinetics of BPS and BPAF.
Topics: Animals; Benzhydryl Compounds; Hazardous Substances; Kinetics; Male; Mice; Phenols; Rats; Sulfones; Toxicity Tests; Toxicokinetics
PubMed: 32985913
DOI: 10.1080/00498254.2020.1829171 -
Journal of Nanobiotechnology Apr 2021The widespread use of nanomaterials (NMs) has raised concerns that exposure to them may introduce potential risks to the human body and environment. The liver is the... (Review)
Review
The widespread use of nanomaterials (NMs) has raised concerns that exposure to them may introduce potential risks to the human body and environment. The liver is the main target organ for NMs. Hepatotoxic effects caused by NMs have been observed in recent studies but have not been linked to liver disease, and the intrinsic mechanisms are poorly elucidated. Additionally, NMs exhibit varied toxicokinetics and induce enhanced toxic effects in susceptible livers; however, thus far, this issue has not been thoroughly reviewed. This review provides an overview of the toxicokinetics of NMs. We highlight the possibility that NMs induce hepatic diseases, including nonalcoholic steatohepatitis (NASH), fibrosis, liver cancer, and metabolic disorders, and explore the underlying intrinsic mechanisms. Additionally, NM toxicokinetics and the potential induced risks in the livers of susceptible individuals, including subjects with liver disease, obese individuals, aging individuals and individuals of both sexes, are summarized. To understand how NM type affect their toxicity, the influences of the physicochemical and morphological (PCM) properties of NMs on their toxicokinetics and toxicity are also explored. This review provides guidance for further toxicological studies on NMs and will be important for the further development of NMs for applications in various fields.
Topics: Animals; Fibrosis; Humans; Hydrophobic and Hydrophilic Interactions; Liver; Liver Diseases; Liver Neoplasms; Metabolic Diseases; Nanostructures; Toxicokinetics
PubMed: 33863340
DOI: 10.1186/s12951-021-00843-2 -
International Journal of Toxicology 2016Nanomaterials, including nanoparticles and nanoobjects, are being incorporated into everyday products at an increasing rate. These products include consumer products of... (Review)
Review
Nanomaterials, including nanoparticles and nanoobjects, are being incorporated into everyday products at an increasing rate. These products include consumer products of interest to toxicologists such as pharmaceuticals, cosmetics, food, food packaging, household products, and so on. The manufacturing of products containing or utilizing nanomaterials in their composition may also present potential toxicologic concerns in the workplace. The molecular complexity and composition of these nanomaterials are ever increasing, and the means and methods being applied to characterize and perform useful toxicologic assessments are rapidly advancing. This article includes presentations by experienced toxicologists in the nanotoxicology community who are focused on the applied aspect of the discipline toward supporting state of the art toxicologic assessments for food products and packaging, pharmaceuticals and medical devices, inhaled nanoparticle and gastrointestinal exposures, and addressing occupational safety and health issues and concerns. This symposium overview article summarizes 5 talks that were presented at the 35th Annual meeting of the American College of Toxicology on the subject of "Applied Nanotechnology."
Topics: Animals; Humans; Nanostructures; Toxicity Tests; Toxicokinetics
PubMed: 26957538
DOI: 10.1177/1091581816628484 -
Toxins Jun 2020One of the concerns when using grain ingredients in feed formulation for livestock and poultry diets is mycotoxin contamination. Aflatoxin, fumonisin, ochratoxin,... (Review)
Review
One of the concerns when using grain ingredients in feed formulation for livestock and poultry diets is mycotoxin contamination. Aflatoxin, fumonisin, ochratoxin, trichothecene (deoxynivalenol, T-2 and HT-2) and zearalenone (ZEN) are mycotoxins that have been frequently reported in animal feed. ZEN, which has raised additional concern due to its estrogenic response in animals, is mainly produced by (), , , , and , and often co-occurs with deoxynivalenol in grains. The commonly elaborated derivatives of ZEN are -zearalenol, -zearalenol, zearalanone, -zearalanol, and -zearalanol. Other modified and masked forms of ZEN (including the extractable conjugated and non-extractable bound derivatives of ZEN) have also been quantified. In this review, common dose of ZEN in animal feed was summarized. The absorption rate, distribution ("carry-over"), major metabolites, toxicity and estrogenicity of ZEN related to poultry, swine and ruminants are discussed.
Topics: Animal Feed; Animal Husbandry; Animals; Dose-Response Relationship, Drug; Estrogens; Food Chain; Food Microbiology; Fungi; Poultry; Risk Assessment; Ruminants; Sus scrofa; Toxicokinetics; Zearalenone
PubMed: 32517357
DOI: 10.3390/toxins12060377 -
Chemical Research in Toxicology May 2018Quantitative predictions of in vivo chemical levels based on in vitro data will become a cornerstone of next generation nonanimal risk evaluations. Both regulatory and...
Quantitative predictions of in vivo chemical levels based on in vitro data will become a cornerstone of next generation nonanimal risk evaluations. Both regulatory and scientific experience with quantitative toxicokinetics must increase now for this transition to happen.
Topics: Animal Testing Alternatives; Animals; Humans; Risk Assessment; Toxicity Tests; Toxicokinetics
PubMed: 29641185
DOI: 10.1021/acs.chemrestox.8b00061