Browsing by Subject "Pharmaceutical Preparations"

Now showing 1 - 8 of 8
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    Developmental exposure of zebrafish to vitamin D receptor acting drugs and environmental toxicants disrupts behavioral function.
    (Neurotoxicology and teratology, 2020-09) Oliveri, Anthony N; Glazer, Lilah; Mahapatra, Debabrata; Kullman, Seth W; Levin, Edward D
    Vitamin D receptor (VDR) signaling is important for optimal neurobehavioral development. Disruption of VDR signaling by environmental toxicants during early development might contribute to the etiology of behavioral dysfunction. In the current set of studies, we examined ten compounds known to affect VDR function in vitro for neurobehavioral effects in vivo in zebrafish. Zebrafish embryos were exposed to concentrations of the compounds in their water during the first 5 days post-fertilization. On day 5, the embryos were tested in an alternating light-dark locomotor assay using a computerized video tracking system. We found that most of the compounds produced significant changes in locomotor behavior in exposed zebrafish larvae, although the direction of the effect (i.e., hypo- or hyperactivity) and the sensitivity of the effect to changes in illumination condition varied across the compounds. The nature of the behavioral effects generally corresponded to the effects these compounds have been shown to exert on VDR. These studies lay a foundation for further investigation to determine whether behavioral dysfunction persists into adulthood and if so which behavioral functions are affected. Zebrafish can be useful for screening compounds identified in high throughput in vitro assays to provide an initial test for how those compounds would affect construction and behavioral function of a complex nervous system, helping to bridge the gap between in vitro neurotoxicity assays and mammalian models for risk assessment in humans.
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    Elucidating the impact of microbial community biodiversity on pharmaceutical biotransformation during wastewater treatment.
    (Microbial biotechnology, 2018-11) Stadler, Lauren B; Delgado Vela, Jeseth; Jain, Sunit; Dick, Gregory J; Love, Nancy G
    In addition to removing organics and other nutrients, the microorganisms in wastewater treatment plants (WWTPs) biotransform many pharmaceuticals present in wastewater. The objective of this study was to examine the relationship between pharmaceutical biotransformation and biodiversity in WWTP bioreactor microbial communities and identify taxa and functional genes that were strongly associated with biotransformation. Dilution-to-extinction of an activated sludge microbial community was performed to establish cultures with a gradient of microbial biodiversity. Batch experiments were performed using the dilution cultures to determine biotransformation extents of several environmentally relevant pharmaceuticals. With this approach, because the communities were all established from the same original community, and using sequencing of the 16S rRNA and metatranscriptome, we identified candidate taxa and genes whose activity and transcript abundances associated with the extent of individual pharmaceutical biotransformation and were lost across the biodiversity gradient. Metabolic genes such as dehydrogenases, amidases and monooxygenases were significantly associated with pharmaceutical biotransformation, and five genera were identified whose activity significantly associated with pharmaceutical biotransformation. Understanding how biotransformation relates to biodiversity will inform the design of biological WWTPs for enhanced removal of chemicals that negatively impact environmental health.
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    Microdosing and drug development: past, present and future.
    (Expert Opin Drug Metab Toxicol, 2013-07) Lappin, Graham; Noveck, Robert; Burt, Tal
    INTRODUCTION: Microdosing is an approach to early drug development where exploratory pharmacokinetic data are acquired in humans using inherently safe sub-pharmacologic doses of drug. The first publication of microdose data was 10 years ago and this review comprehensively explores the microdose concept from conception, over the past decade, up until the current date. AREAS COVERED: The authors define and distinguish the concept of microdosing from similar approaches. The authors review the ability of microdosing to provide exploratory pharmacokinetics (concentration-time data) but exclude microdosing using positron emission tomography. The article provides a comprehensive review of data within the peer-reviewed literature as well as the latest applications and a look into the future, towards where microdosing may be headed. EXPERT OPINION: Evidence so far suggests that microdosing may be a better predictive tool of human pharmacokinetics than alternative methods and combination with physiologically based modelling may lead to much more reliable predictions in the future. The concept has also been applied to drug-drug interactions, polymorphism and assessing drug concentrations over time at its site of action. Microdosing may yet have more to offer in unanticipated directions and provide benefits that have not been fully realised to date.
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    Prediction of short-term antidepressant response using probabilistic graphical models with replication across multiple drugs and treatment settings.
    (Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021-06) Athreya, Arjun P; Brückl, Tanja; Binder, Elisabeth B; John Rush, A; Biernacka, Joanna; Frye, Mark A; Neavin, Drew; Skime, Michelle; Monrad, Ditlev; Iyer, Ravishankar K; Mayes, Taryn; Trivedi, Madhukar; Carter, Rickey E; Wang, Liewei; Weinshilboum, Richard M; Croarkin, Paul E; Bobo, William V
    Heterogeneity in the clinical presentation of major depressive disorder and response to antidepressants limits clinicians' ability to accurately predict a specific patient's eventual response to therapy. Validated depressive symptom profiles may be an important tool for identifying poor outcomes early in the course of treatment. To derive these symptom profiles, we first examined data from 947 depressed subjects treated with selective serotonin reuptake inhibitors (SSRIs) to delineate the heterogeneity of antidepressant response using probabilistic graphical models (PGMs). We then used unsupervised machine learning to identify specific depressive symptoms and thresholds of improvement that were predictive of antidepressant response by 4 weeks for a patient to achieve remission, response, or nonresponse by 8 weeks. Four depressive symptoms (depressed mood, guilt feelings and delusion, work and activities and psychic anxiety) and specific thresholds of change in each at 4 weeks predicted eventual outcome at 8 weeks to SSRI therapy with an average accuracy of 77% (p = 5.5E-08). The same four symptoms and prognostic thresholds derived from patients treated with SSRIs correctly predicted outcomes in 72% (p = 1.25E-05) of 1996 patients treated with other antidepressants in both inpatient and outpatient settings in independent publicly-available datasets. These predictive accuracies were higher than the accuracy of 53% for predicting SSRI response achieved using approaches that (i) incorporated only baseline clinical and sociodemographic factors, or (ii) used 4-week nonresponse status to predict likely outcomes at 8 weeks. The present findings suggest that PGMs providing interpretable predictions have the potential to enhance clinical treatment of depression and reduce the time burden associated with trials of ineffective antidepressants. Prospective trials examining this approach are forthcoming.
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    Priorities for the Priority Review Voucher.
    (Am J Trop Med Hyg, 2017-01-11) Ridley, David B
    The U.S. Congress created the priority review voucher program in 2007 to encourage development of drugs for neglected diseases. Under the voucher program, the developer of a drug for a neglected or rare pediatric disease that is approved by the U.S. Food and Drug Administration receives a bonus priority review voucher for another drug. As of 2016, four vouchers have sold for an average price of $200 million. Recent experience with the voucher program indicates strengths and weaknesses of the program, as well as a need for legislative changes.
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    Quantifying the utility of taking pills for preventing adverse health outcomes: a cross-sectional survey.
    (BMJ Open, 2015-05-11) Hutchins, Robert; Pignone, Michael P; Sheridan, Stacey L; Viera, Anthony J
    OBJECTIVES: The utility value attributed to taking pills for prevention can have a major effect on the cost-effectiveness of interventions, but few published studies have systematically quantified this value. We sought to quantify the utility value of taking pills used for prevention of cardiovascular disease (CVD). DESIGN: Cross-sectional survey. SETTING: Central North Carolina. PARTICIPANTS: 708 healthcare employees aged 18 years and older. PRIMARY AND SECONDARY OUTCOMES: Utility values for taking 1 pill/day, assessed using time trade-off, modified standard gamble and willingness-to-pay methods. RESULTS: Mean age of respondents was 43 years (19-74). The majority of the respondents were female (83%) and Caucasian (80%). Most (80%) took at least 2 pills/day. Mean utility values for taking 1 pill/day using the time trade-off method were: 0.9972 (95% CI 0.9962 to 0.9980). Values derived from the standard gamble and willingness-to-pay methods were 0.9967 (0.9954 to 0.9979) and 0.9989 (95% CI 0.9986 to 0.9991), respectively. Utility values varied little across characteristics such as age, sex, race, education level or number of pills taken per day. CONCLUSIONS: The utility value of taking pills daily in order to prevent an adverse CVD health outcome is approximately 0.997.
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    Quantum dot-based theranostics.
    (Nanoscale, 2010-01) Ho, Yi-Ping; Leong, Kam W
    Luminescent semiconductor nanocrystals, also known as quantum dots (QDs), have advanced the fields of molecular diagnostics and nanotherapeutics. Much of the initial progress for QDs in biology and medicine has focused on developing new biosensing formats to push the limit of detection sensitivity. Nevertheless, QDs can be more than passive bio-probes or labels for biological imaging and cellular studies. The high surface-to-volume ratio of QDs enables the construction of a "smart" multifunctional nanoplatform, where the QDs serve not only as an imaging agent but also a nanoscaffold catering for therapeutic and diagnostic (theranostic) modalities. This mini review highlights the emerging applications of functionalized QDs as fluorescence contrast agents for imaging or as nanoscale vehicles for delivery of therapeutics, with special attention paid to the promise and challenges towards QD-based theranostics.
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    Should the patent system for new medicines be abolished?
    (Clin Pharmacol Ther, 2007-11) DiMasi, JA; Grabowski, HG