Trends in microdosing and other exploratory human pharmacokinetic studies for early drug development

Bioanalysis ◽  
2010 ◽  
Vol 2 (3) ◽  
pp. 377-379 ◽  
Author(s):  
Berend Oosterhuis
1992 ◽  
Vol 11 (3) ◽  
pp. 303-308
Author(s):  
Judi Weissinger

Kinetic, dynamic, and metabolic data can be used to predict the appropriate studies, doses, duration, route of administration, species, and dosage interval in toxicology studies coordinated with drug development. These data are used to predict starting and maximal doses in human studies, and when evaluated in conjunction with the data obtained in human pharmacokinetic studies, serve as an index for animal to human comparisons and extrapolations. The optimal use of kinetic and dynamic information in standard pharmacologic and toxicologic studies will be presented. Reference will be made to problems encountered in the absence of these data and protocol development advantages where these data are incorporated. Developmental of pharmaceuticals, without incorporating kinetic and dynamic information, is currently associated with more costly, more time consuming, less utilizable knowledge and subsequent studies are often needed to explain anomalous results.


2015 ◽  
Vol 289 (3) ◽  
pp. 525-533 ◽  
Author(s):  
Wenhu Huang ◽  
Walter Collette ◽  
Michelle Twamley ◽  
Shirley A. Aguirre ◽  
Aida Sacaan

2021 ◽  
Vol 12 ◽  
Author(s):  
Rodrigo Cuiabano Paes Leme ◽  
Raquel Bandeira da Silva

It has been demonstrated that some non-steroidal anti-inflammatory drugs (NSAIDs), like acetylsalicylic acid, diclofenac, and ibuprofen, have anti-biofilm activity in concentrations found in human pharmacokinetic studies, which could fuel an interest in repurposing these well tolerated drugs as adjunctive therapies for biofilm-related infections. Here we sought to review the currently available data on the anti-biofilm activity of NSAIDs and its relevance in a clinical context. We performed a systematic literature review to identify the most commonly tested NSAIDs drugs in the last 5 years, the bacterial species that have demonstrated to be responsive to their actions, and the emergence of resistance to these molecules. We found that most studies investigating NSAIDs’ activity against biofilms were in vitro, and frequently tested non-clinical bacterial isolates, which may not adequately represent the bacterial populations that cause clinically-relevant biofilm-related infections. Furthermore, studies concerning NSAIDs and antibiotic resistance are scarce, with divergent outcomes. Although the potential to use NSAIDs to control biofilm-related infections seems to be an exciting avenue, there is a paucity of studies that tested these drugs using appropriate in vivo models of biofilm infections or in controlled human clinical trials to support their repurposing as anti-biofilm agents.


Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1397 ◽  
Author(s):  
Sidney J. Stohs ◽  
Oliver Chen ◽  
Sidhartha D. Ray ◽  
Jin Ji ◽  
Luke R. Bucci ◽  
...  

Curcumin exerts a wide range of beneficial physiological and pharmacological activities, including antioxidant, anti-amyloid, anti-inflammatory, anti-microbial, anti-neoplastic, immune-modulating, metabolism regulating, anti-depressant, neuroprotective and tissue protective effects. However, its poor solubility and poor absorption in the free form in the gastrointestinal tract and its rapid biotransformation to inactive metabolites greatly limit its utility as a health-promoting agent and dietary supplement. Recent advances in micro- and nano-formulations of curcumin with greatly enhanced absorption resulting in desirable blood levels of the active forms of curcumin now make it possible to address a wide range of potential applications, including pain management, and as tissue protective. Using these forms of highly bioavailable curcumin now enable a broad spectrum of appropriate studies to be conducted. This review discusses the formulations designed to enhance bioavailability, metabolism of curcumin, relationships between solubility and particle size relative to bioavailability, human pharmacokinetic studies involving formulated curcumin products, the widely used but inappropriate practice of hydrolyzing plasma samples for quantification of blood curcumin, current applications of curcumin and its metabolites and promising directions for health maintenance and applications.


2018 ◽  
Vol 24 (5) ◽  
pp. 560-574 ◽  
Author(s):  
Aymeric Ousset ◽  
Céline Bassand ◽  
Pierre-François Chavez ◽  
Joke Meeus ◽  
Florent Robin ◽  
...  

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