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Reflection paper on investigation of pharmacokinetics in the obese population - Scientific guideline

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onsdag, februari 14, 2024

Leptin, PD, Metabolism, Toxicity, Body composition, Ciprofloxacin, Clinical Pharmacokinetics, Water, LBW, Perfusion, LBM, Canadian International Council, AUC, PLOS One, Bariatric surgery, Clopidogrel, CYP, Breast, Health, DNA-binding protein, BMC Public Health, Pharmacology, BMI, CRP, Pharmaceutical Research (journal), Organ, Draft, Guideline, Bypass surgery, WHO, Ageing, INT, Pharmacokinetics, Liver, Bioavailability, Chronic liver disease, Human, Incidence, Committee, Absorption, TBW, Cardiovascular disease, Anatomy, CYP2C19, PBPK, Cmax, Factorization of polynomials, European, Lancet, CHMP, Journal, NASH, Pharmacotherapy, Adipose tissue, Non-alcoholic fatty liver disease, Journal of Clinical Investigation, Medication package insert, Overweight, NPS MedicineWise, Permeability, Benzodiazepine, Meta-analysis, Liver disease, Half-life, Acetylcholine, Ciclosporin, AAG, Kinetics, Midazolam, Kidney, Safety, Biomarker, Clinical Pharmacology & Therapeutics, Peptide, Classification, Hypertension, Metabolic syndrome, Acute coronary syndrome, Insulin resistance, Fatty liver disease, CYP2E1, Lithium, Body mass index, Reproduction, EMA, IBW, Injection, Anker, NCA, Enzyme, Inflammation, Cancer, Weight loss, Gastrointestinal tract, Cardiac output, Public health, Adipokine, CYP2C9, E pluribus unum, Physiology, Agency, Risk, Steroid, Lymph, CYP2D6, BSA, GI, Cytokine, Systematic review, Vaccine

Reflection paper on investigations of pharmacokinetics in

Key Points:

Reflection paper on investigations of pharmacokinetics in
the obese population
Table of contents
1.
References .............................................................................................. 9
Reflection paper on investigations of pharmacokinetics in the obese population
EMA/CHMP/535116/2016

Page 2/12

1.
This is considered
a shortcoming that is potentially compounded by obese patients often being poorly represented in
clinical studies.
The specific aims of this reflection paper are to:
?
describe how the effects of obesity can be investigated during clinical medicinal product
development.
?
provide recommendations on when investigations of the effect of obesity on the PK of a
medicinal product should be particularly considered.
Reflection paper on investigations of pharmacokinetics in the obese population
EMA/CHMP/535116/2016
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?

discuss how to reflect PK (and/or PK/PD) findings in weight/weight-based dosing
recommendations.
Absorption
Reduced rate of absorption linked to locally reduced blood flow (8) is reported for the subcutaneous
and transdermal routes in obese subjects.
Distribution
The distribution of medicinal products is driven by body composition, regional blood flow and binding to
tissue and plasma proteins.
Obese subjects have a larger absolute lean body weight (LBW) as well as fat mass.
The physicochemical properties of a medicinal product (lipophilicity, polarity, molecular size, and
degree of ionization) influence its distribution in the body.
In BMI class III obese
subjects, the blood flow per gram of fat is significantly lower than that observed in class I obese or
lean subjects (4).
Reflection paper on investigations of pharmacokinetics in the obese population
EMA/CHMP/535116/2016
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An increased amount of alpha-1-acid-glycoprotein (AAG), linked to a chronic inflammatory state, is
reported in obese individuals.
Fatty infiltrations are present in the liver for 90% of obese subjects, with the extent of the infiltrations
being proportional to the degree of obesity.
In some cases, in particular for CYP3A4 metabolized medicinal products,
bodyweight normalized clearance can be lower in obese patients (23).
Based on presently available data, it has been suggested that uptake transporters
Reflection paper on investigations of pharmacokinetics in the obese population
EMA/CHMP/535116/2016

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are downregulated while efflux transporters may be upregulated (31).
Platelet hyper-reactivity is also observed,
which can impair the response to anti-platelet medicinal products in obese patients (42, 43).
Reflection paper on investigations of pharmacokinetics in the obese population
EMA/CHMP/535116/2016
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3.

the medicinal product properties and scientific literature indicate that obesity may lead to a
marked effect on elimination and/or distribution or on the PK/PD relationship.
These
models may aid in extrapolating the known efficacy and safety in the non-obese population to the
obese population.
The Pharmacokinetics of the CYP3A Substrate Midazolam in Morbidly Obese Patients
Before and One Year After Bariatric Surgery.
Reflection paper on investigations of pharmacokinetics in the obese population
EMA/CHMP/535116/2016
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41.
Reflection paper on investigations of pharmacokinetics in the obese population
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Chung-Ang University Team Achieves High-Safety Ultra-Fast Charging for Lithium Batteries

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tisdag, februari 6, 2024

Lithium, Attention, Kinetics, Lithium hexafluorophosphate, Carbonate, Climate change, Safety, Carbon, EV, Energy Storage Materials, Chung-Ang University, Associate, Health, Engineering, Electrolyte, Electric battery

SEOUL, South Korea, Feb. 6, 2024 /PRNewswire/ -- Lithium-ion (Li-ion) batteries are indispensable for modern devices like electric vehicles, which are playing an increasingly crucial role in people's lives. However, to fully electrify vehicles with Li-ion batteries, the main hurdle is achieving rapid charging without compromising energy density. The convenience and acceptance of electric vehicles by consumers are also influenced by factors such as their range and charging times. Additionally, the utilization of Li plating for ultra-fast charging raises safety concerns due to high cell polarization, requiring careful attention.

Key Points:

However, to fully electrify vehicles with Li-ion batteries, the main hurdle is achieving rapid charging without compromising energy density.
The convenience and acceptance of electric vehicles by consumers are also influenced by factors such as their range and charging times.
Additionally, the utilization of Li plating for ultra-fast charging raises safety concerns due to high cell polarization, requiring careful attention.
Title of original paper: Boosting interfacial kinetics in extremely fast rechargeable Li-ion batteries with linear carbonate-based, LiPF6-concentrated electrolyte

ARRALYZE® Launches CellShepherd®: A Fully Autonomous Single-Cell Platform For Real-Time Monitoring Of Functional Assays

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tisdag, februari 6, 2024

Glass, Kinetics, Miniaturization, Cell, Laboratory

After a successful beta-testing phase in 2023, this groundbreaking platform is now ready to revolutionize cell-based research and development across biomedical and various life science fields.

Key Points:

After a successful beta-testing phase in 2023, this groundbreaking platform is now ready to revolutionize cell-based research and development across biomedical and various life science fields.
CellShepherd®, developed by ARRALYZE®, responds to the urgent need for advanced functional cell screening technologies in academic and industrial laboratories.
It stands out with ARRALYZE’s proprietary nanowell glass arrays, which miniaturize cell-based assays while enabling real-time monitoring at the single-cell level.
This autonomous platform boasts precise dispensing into nanoliter glass wells and supports (co)-culturing under climate-controlled, sterile conditions.

Bruker Introduces the Ingenious Novel ‘Triceratops’ SPR #64 Surface Plasmon Resonance System for Drug Discovery at SLAS2024

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måndag, februari 5, 2024

At the SLAS2024 International Conference and Exhibition , Bruker Corporation (Nasdaq: BRKR) today introduced the ground-breaking, new ‘Triceratops’ SPR #64 Surface Plasmon Resonance (SPR) instrument.

Key Points:

At the SLAS2024 International Conference and Exhibition , Bruker Corporation (Nasdaq: BRKR) today introduced the ground-breaking, new ‘Triceratops’ SPR #64 Surface Plasmon Resonance (SPR) instrument.
The SPR #64 system has been engineered from the bottom up to accelerate drug discovery with increased SPR throughput, leading sensitivity and data quality.
View the full release here: https://www.businesswire.com/news/home/20240205314598/en/
‘Triceratops’ SPR #64: the all new, high-throughput multiplexing Surface Plasmon Resonance (SPR) system (Photo: Business Wire)
The ‘Triceratops’ SPR #64 system combines highest sensitivity detection with a novel microfluidics concept, which via the perpendicular rotation of the 8-channel flow cell, now facilitates the simultaneous reading of 64 sensor spots.
With the ‘Triceratops’ SPR #64, Bruker is now offering drug discovery customers the highest throughput in the industry with uncompromising data quality.

RTX's CHIMERA high-power microwave system excels during three-week field test

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måndag, januari 29, 2024

Engineering, Conventional weapon, Kinetics, Raytheon Technologies, Advanced technology, Radio, Partnership, Government, AFRL, Defense, HPM, Air Force Research Laboratory, Research, Arms industry

WHITE SANDS, N.M., Jan. 29, 2024 /PRNewswire/ -- The Air Force Research Laboratory and Raytheon, an RTX (NYSE: RTX) business, have successfully completed a three-week field test of the CHIMERA high-power microwave (HPM) weapon at White Sands Missile Range in New Mexico. During the test, CHIMERA applied directed energy to multiple static target variations and demonstrated end-to-end fire control by acquiring and tracking aerial targets and maintaining tracking for the entire flight path.

Key Points:

During the test, CHIMERA applied directed energy to multiple static target variations and demonstrated end-to-end fire control by acquiring and tracking aerial targets and maintaining tracking for the entire flight path.
The Counter-Electronic High-Power Microwave Extended-Range Air Base Defense system, known as CHIMERA, was built to fire highly concentrated radio energy at multiple middle-to-long-range targets.
The ground-based demonstration system wields more power than other HPM systems to defeat airborne threats at the speed of light.
CHIMERA is part of the Directed Energy Front-line Electromagnetic Neutralization and Defeat (DEFEND) program , which is a joint service effort to design, build and test HPM systems for front-line deployment.

LyondellBasell Launches Petrothene T3XL7420: A Revolutionary Polymer Compound for Optimized Manufacturing

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tisdag, januari 23, 2024

CSA, SAE, CSA Group, International Organization (journal), Chemical industry, Kinetics, SAE International, LyondellBasell, International Organization for Standardization, UL, ISO, UL (safety organization), LYB

HOUSTON, Jan. 23, 2024 /PRNewswire/ -- LyondellBasell (LYB), a global leader in the chemical industry, is proud to announce the release of a cross-linkable, all-in-one flame-retardant compound, Petrothene T3XL7420, which is expected to deliver considerable cost savings while streamlining manufacturing processes.

Key Points:

HOUSTON, Jan. 23, 2024 /PRNewswire/ -- LyondellBasell (LYB), a global leader in the chemical industry, is proud to announce the release of a cross-linkable, all-in-one flame-retardant compound, Petrothene T3XL7420, which is expected to deliver considerable cost savings while streamlining manufacturing processes.
This new product offering also improves the quality of end products for wire producers in the automotive and appliance industries.
Based on customer demand and industry need, LyondellBasell designed this innovative compound to address the need to optimize production line speeds and enhance manufacturing efficiency.
Petrothene T3XL7420 has undergone rigorous testing and certification processes to ensure its quality and reliability.

Cellply launches its end-to-end single cell potency characterization platform VivaCyte

Retrieved on:

onsdag, januari 17, 2024

Doctor of Philosophy, Cell, Phenotype, Kinetics, Research, Heart, Quality control, Drug discovery, Vaccine

VivaCyte enables rapid testing of multiple cell therapy candidates from multiple process options, against multiple target tumor cells.

Key Points:

VivaCyte enables rapid testing of multiple cell therapy candidates from multiple process options, against multiple target tumor cells.
Unprecedented depth of analysis combined with parallel screening of multiple conditions in a single run, delivers reproducible immune cell characterization and single-cell functional characterization at a fraction of the time currently needed by existing analytical tools.
"Helping the biopharmaceutical industry to identify and develop the most effective versions of their cellular therapies is our goal," stated Emiliano Spagnolo, CEO, Cellply.
"We have seen an explosion in the demand for a characterization platform capable of rapidly measuring the potential effectiveness of these game-changing cellular immunotherapies and accelerating their development.

Cellply launches its end-to-end single cell potency characterization platform VivaCyte

Retrieved on:

onsdag, januari 17, 2024

Doctor of Philosophy, Cell, Phenotype, Kinetics, Research, Heart, Quality control, Drug discovery, Vaccine

VivaCyte enables rapid testing of multiple cell therapy candidates from multiple process options, against multiple target tumor cells.

Key Points:

VivaCyte enables rapid testing of multiple cell therapy candidates from multiple process options, against multiple target tumor cells.
Unprecedented depth of analysis combined with parallel screening of multiple conditions in a single run, delivers reproducible immune cell characterization and single-cell functional characterization at a fraction of the time currently needed by existing analytical tools.
"Helping the biopharmaceutical industry to identify and develop the most effective versions of their cellular therapies is our goal," stated Emiliano Spagnolo, CEO, Cellply.
"We have seen an explosion in the demand for a characterization platform capable of rapidly measuring the potential effectiveness of these game-changing cellular immunotherapies and accelerating their development.

Gwangju Institute of Science and Technology Researchers Unveil Useful Strategies for Sustainable Gas Storage and Separation with Clathrate Hydrates

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tisdag, januari 9, 2024

CO2, Kinetics, Natural gas, Research, Professor, Temperature, Power, Permafrost, Gas, Accounts of Chemical Research, Hydrogen, Carbon dioxide, Carbon, Climate change, Hydrate, Water, Transport, Clathrate compound

In a new study led by Professor Youngjune Park from the Gwangju Institute of Science and Technology in Korea, a team of researchers has comprehensively reviewed recent research findings, including their own, that address these myriad challenges associated with clathrate hydrates.

Key Points:

In a new study led by Professor Youngjune Park from the Gwangju Institute of Science and Technology in Korea, a team of researchers has comprehensively reviewed recent research findings, including their own, that address these myriad challenges associated with clathrate hydrates.
According to Prof. Park: "By exploring the untapped potential of clathrate hydrates, we have effectively mitigated these limitations and provided efficient hydrogen (H2) storage solutions through the introduction of hydrogen-natural gas blends into clathrate hydrates."
"This research has significant long-term potential for the gas storage and separation industry, particularly in achieving carbon neutrality.
Title of original paper: Advances in Nanomaterials for Sustainable Gas Separation and Storage: Focus on Clathrate Hydrates

Atea Pharmaceuticals Announces Positive Initial Data from Phase 2 Study for Hepatitis C Virus (HCV) and Significant Enrollment Milestone for Phase 3 SUNRISE-3 Trial for COVID-19

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måndag, januari 8, 2024

BOSTON, Jan. 08, 2024 (GLOBE NEWSWIRE) -- Atea Pharmaceuticals, Inc. (Nasdaq: AVIR) (“Atea”), a clinical-stage biopharmaceutical company engaged in the discovery and development of oral antiviral therapeutics for serious viral diseases, today announced the achievement of two significant clinical milestones from its Hepatitis C Virus (HCV) and COVID-19 programs. The Company reported positive initial data from the first 52 patients in the lead-in cohort of its Phase 2 combination 8-week study of bemnifosbuvir and ruzasvir (RZR) for the treatment of HCV. Additionally, Atea has enrolled more than 650 patients in the monotherapy arm of its Phase 3 SUNRISE-3 trial for the treatment of COVID-19, and enrollment continues with the current wave. This enrollment milestone allows for the first interim analysis of the study by the DSMB, which is expected this March.

Key Points:

This enrollment milestone allows for the first interim analysis of the study by the DSMB, which is expected this March.
“We are excited to share that the initial data from the Phase 2 combination 8-week study showed a 98% SVR4, which exceeds our efficacy criterion of >90% for continuing the study.
Preliminary data are being presented as available, with SVR4 data currently available from 52 of the 60 lead-in patients.
The primary endpoint of the trial is all-cause hospitalization or death through Day 29 post-treatment in the monotherapy arm in 2,200 patients.