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PMC11236904
core_pubmed_pmc
Dalzanemdor (SAGE‐718), a novel, investigational N‐methyl‐D‐aspartate receptor positive allosteric modulator: Safety, tolerability, and clinical pharmacology in randomized dose‐finding studies in healthy participants and an open‐label study in participants with Huntington's disease
Dalzanemdor (SAGE‐718), a novel, investigational N‐methyl‐D‐aspartate receptor positive allosteric modulator: Safety, tolerability, and clinical pharmacology in randomized dose‐finding studies in healthy participants and an open‐label study in participants with Huntington's disease Abstract Abstract N‐methyl‐D‐aspartat...
PMC4063859
core_pubmed_pmc
Effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and relevant pharmacological interventions on fall risk in elderly patients
Effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and relevant pharmacological interventions on fall risk in elderly patients Abstract Abstract Background Falls among the elderly are an issue internationally and a public health problem that brings substantial economic and qu...
PMC7164401
core_pubmed_pmc
Relative bioavailability and pharmacokinetic comparison of calcium glucoheptonate with calcium carbonate
Relative bioavailability and pharmacokinetic comparison of calcium glucoheptonate with calcium carbonate Abstract Abstract Adequate calcium intake is important for the prevention of bone loss and osteoporosis. For some populations such as those of Southeast Asia where calcium intake is very low, supplements represent a...
PMC12304869
core_pubmed_pmc
Long‐acting PYY 3 −36 analogue with semaglutide for obesity: from preclinical assessment through randomized clinical studies
Long‐acting PYY 3 −36 analogue with semaglutide for obesity: from preclinical assessment through randomized clinical studies Abstract Abstract Objective The hormone peptide YY (PYY; cleaved into Y 2 ‐selective form PYY 3‐36 ) is an attractive candidate for use as a complementary pharmacotherapy for obesity along with g...
PMC10215934
core_pubmed_pmc
Daptomycin Pharmacokinetics in Blood and Wound Fluid in Critical Ill Patients with Left Ventricle Assist Devices
Daptomycin Pharmacokinetics in Blood and Wound Fluid in Critical Ill Patients with Left Ventricle Assist Devices Abstract Abstract Daptomycin is a cyclic lipopeptide antibiotic with bactericidal effects against multidrug-resistant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and ...
PMC10779271
core_pubmed_pmc
Biotransformation of Δ 1 -Progesterone Using Selected Entomopathogenic Filamentous Fungi and Prediction of Its Products’ Bioactivity
Biotransformation of Δ 1 -Progesterone Using Selected Entomopathogenic Filamentous Fungi and Prediction of Its Products’ Bioactivity Abstract Abstract This research aimed at obtaining new derivatives of pregn-1,4-diene-3,20-dione (Δ 1 -progesterone) ( 2 ) through microbiological transformation. For the role of catalyst...
PMC8400955
core_pubmed_pmc
Fulvestrant-3-Boronic Acid (ZB716) Demonstrates Oral Bioavailability and Favorable Pharmacokinetic Profile in Preclinical ADME Studies
Fulvestrant-3-Boronic Acid (ZB716) Demonstrates Oral Bioavailability and Favorable Pharmacokinetic Profile in Preclinical ADME Studies Abstract Abstract Fulvestrant-3-boronic acid (ZB716), an oral selective estrogen receptor degrader (SERD) under clinical development, has been investigated in ADME studies to characteri...
PMC12191206
core_pubmed_pmc
Analysis of Tacrolimus Clearance in Patients with Kidney Transplants from Romania
Analysis of Tacrolimus Clearance in Patients with Kidney Transplants from Romania Abstract Background/Objectives : Tacrolimus is a key immunosuppressant in kidney transplantation, but its high interindividual pharmacokinetic variability complicates dosing. This study aimed to develop a population pharmacokinetic model ...
PMC10097687
core_pubmed_pmc
Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders
Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders Abstract Clearance of neurotoxic brain proteins via cerebrospinal fluid (CSF) to blood has recently emerged to be crucial, and plasma biomarkers of neurodegeneration were newly introduc...
PMC8956633
core_pubmed_pmc
Safety, pharmacokinetics, and pharmacodynamics of milvexian in healthy Japanese participants
Safety, pharmacokinetics, and pharmacodynamics of milvexian in healthy Japanese participants Abstract Abstract This randomized, double-blind, placebo-controlled, multiple ascending–dose study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of milvexian, an oral small-molecule FX...
PMC9008922
core_pubmed_pmc
Advanced pharmacodynamics of cangrelor in healthy volunteers: a dose-finding, open-label, pilot trial
Advanced pharmacodynamics of cangrelor in healthy volunteers: a dose-finding, open-label, pilot trial Abstract Abstract Background High on-treatment platelet reactivity (HTPR) remains a major problem in the acute management of ST-elevation myocardial infarction (STEMI), leading to higher rates of stent thrombosis and m...
PMC11373226
core_pubmed_pmc
Assessment of pharmacokinetics-pharmacodynamics to support omadacycline dosing regimens for the treatment of patients with acute bacterial skin and skin structure infections
Assessment of pharmacokinetics-pharmacodynamics to support omadacycline dosing regimens for the treatment of patients with acute bacterial skin and skin structure infections Abstract ABSTRACT Pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy were evaluated using data from omadacycline-treated patients ...
PMC6284260
core_pubmed_pmc
Tolerance, Variability and Pharmacokinetics of Albumin-Bound Paclitaxel in Chinese Breast Cancer Patients
Tolerance, Variability and Pharmacokinetics of Albumin-Bound Paclitaxel in Chinese Breast Cancer Patients Abstract Objective: The aim of this study was to explore the tolerance, variability, and pharmacokinetics (PK) of albumin-bound paclitaxel (QL, HR, ZDTQ) among Chinese breast cancer patients. Methods: Three randomi...
PMC10948391
core_pubmed_pmc
Making drugs from T cells: The quantitative pharmacology of engineered T cell therapeutics
Making drugs from T cells: The quantitative pharmacology of engineered T cell therapeutics Abstract Engineered T cells have emerged as highly effective treatments for hematological cancers. Hundreds of clinical programs are underway in efforts to expand the efficacy, safety, and applications of this immuno-therapeutic ...
PMC9446899
core_pubmed_pmc
Anti-Extra Domain B Splice Variant of Fibronectin Antibody–Drug Conjugate Eliminates Tumors with Enhanced Efficacy When Combined with Checkpoint Blockade
Anti-Extra Domain B Splice Variant of Fibronectin Antibody–Drug Conjugate Eliminates Tumors with Enhanced Efficacy When Combined with Checkpoint Blockade Abstract Abstract Extra domain B splice variant of fibronectin (EDB+FN) is an extracellular matrix protein (ECM) deposited by tumor-associated fibroblasts, and is ass...
PMC10780910
core_pubmed_pmc
Opioid/Dopamine Receptor Binding Studies, NMR and Molecular Dynamics Simulation of LENART01 Chimera, an Opioid-Bombesin-like Peptide
Opioid/Dopamine Receptor Binding Studies, NMR and Molecular Dynamics Simulation of LENART01 Chimera, an Opioid-Bombesin-like Peptide Abstract Abstract The design and development of hybrid compounds as a new class of drug candidates remains an excellent opportunity to improve the pharmacological properties of drugs (inc...
PMC6784292
core_pubmed_pmc
Bioisosteres of Carbohydrate Functional Groups in Glycomimetic Design
Bioisosteres of Carbohydrate Functional Groups in Glycomimetic Design Abstract Abstract The aberrant presentation of carbohydrates has been linked to a number of diseases, such as cancer metastasis and immune dysregulation. These altered glycan structures represent a target for novel therapies by modulating their assoc...
PMC9543385
core_pubmed_pmc
Population pharmacokinetics and exposure–response of anti‐programmed cell death protein‐1 monoclonal antibody dostarlimab in advanced solid tumours
Population pharmacokinetics and exposure–response of anti‐programmed cell death protein‐1 monoclonal antibody dostarlimab in advanced solid tumours Abstract Abstract Aim Develop a population pharmacokinetic (PopPK) model to characterise the pharmacokinetics (PK) of anti‐programmed cell death protein‐1 (PD‐1) antibody d...
PMC12617853
core_pubmed_pmc
Perfluorinated chemicals and adolescent respiratory health: Epidemiological evidence and mechanistic insights
Perfluorinated chemicals and adolescent respiratory health: Epidemiological evidence and mechanistic insights Abstract Perfluorinated compounds (PFCs) are persistent environmental pollutants with near-universal human exposure, yet their respiratory health impacts during adolescence remain insufficiently explored. This ...
PMC12291830
core_pubmed_pmc
Preclinical Study of Pharmacokinetic/Pharmacodynamic Analysis of Tebipenem Using Monte Carlo Simulation for Extended-Spectrum β-Lactamase-Producing Bacterial Urinary Tract Infections in Japanese Patients According to Renal Function
Preclinical Study of Pharmacokinetic/Pharmacodynamic Analysis of Tebipenem Using Monte Carlo Simulation for Extended-Spectrum β-Lactamase-Producing Bacterial Urinary Tract Infections in Japanese Patients According to Renal Function Abstract Abstract Background/Objectives: The increasing prevalence of urinary tract infe...
PMC7693231
core_pubmed_pmc
Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban
Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban Abstract Rivaroxaban (RIV) is commonly prescribed with carbamazepine or phenytoin (CBZ/PHT) in post-stroke seizure or post-stroke epilepsy patients. Although adverse events have been reported in several previous studies when ...
PMC12388889
core_pubmed_pmc
Anti-PEG Antibodies and Their Biological Impact on PEGylated Drugs: Challenges and Strategies for Optimization
Anti-PEG Antibodies and Their Biological Impact on PEGylated Drugs: Challenges and Strategies for Optimization Abstract Abstract Polyethylene glycol (PEG) has been widely utilized in optimizing therapeutics due to its excellent biocompatibility and chemical stability. However, multiple dosing of PEGylated drugs may res...
PMC4156804
core_pubmed_pmc
Use of probiotics to correct dysbiosis of normal microbiota following disease or disruptive events: a systematic review
Use of probiotics to correct dysbiosis of normal microbiota following disease or disruptive events: a systematic review Abstract Abstract Objective To assess the evidence for the claim probiotics can correct dysbiosis of the normal microbiota resulting from disease or disruptive events. Setting Systematic review of pub...
PMC9326246
core_pubmed_pmc
Neurotoxicity of Engineered Nanomaterials: Testing Considerations
Neurotoxicity of Engineered Nanomaterials: Testing Considerations Abstract Abstract As with toxicology in general, major challenges have emerged in its subfield neurotoxicology regarding the testing of engineered nanomaterials (ENM). This is on the one hand due to their complex physicochemical properties, like size, sp...
PMC9652412
core_pubmed_pmc
Ruxolitinib and exemestane for estrogen receptor positive, aromatase inhibitor resistant advanced breast cancer
Ruxolitinib and exemestane for estrogen receptor positive, aromatase inhibitor resistant advanced breast cancer Abstract Abstract Circulating IL-6, an activator of JAK/STAT signaling, is associated with poor prognosis and aromatase inhibitor (AI) resistance in hormone-receptor positive (HR+) breast cancer. Here we repo...
PMC12897889
core_pubmed_pmc
From Population-Based PBPK to Individualized Virtual Twins: Clinical Validation and Applications in Medicine
From Population-Based PBPK to Individualized Virtual Twins: Clinical Validation and Applications in Medicine Abstract Abstract Physiologically based pharmacokinetic (PBPK) models are widely used in the context of personalized medicine, as they allow for the evaluation of dosing schedules and routes of administration by...
PMC6619746
core_pubmed_pmc
Single nucleotide polymorphisms associated with elevated alanine aminotransferase in patients receiving asunaprevir plus daclatasvir combination therapy for chronic hepatitis C
Single nucleotide polymorphisms associated with elevated alanine aminotransferase in patients receiving asunaprevir plus daclatasvir combination therapy for chronic hepatitis C Abstract Aims Drug-induced liver damage characterized by serum alanine aminotransferase (ALT) elevation often occurs in direct-acting antiviral...
PMC9162170
core_pubmed_pmc
Pharmacokinetic Exposures Associated With Oral Administration of Sorafenib in Dogs With Spontaneous Tumors
Pharmacokinetic Exposures Associated With Oral Administration of Sorafenib in Dogs With Spontaneous Tumors Abstract Sorafenib is a multi-kinase small molecule inhibitor that targets serine/threonine and tyrosine kinases including the RAF kinase family, VEGFR-2, and PDGFR. The aim of this study was to evaluate the syste...
PMC7416922
core_pubmed_pmc
Benefit of serum drug monitoring complementing urine analysis to assess adherence to antihypertensive drugs in first-line therapy
Benefit of serum drug monitoring complementing urine analysis to assess adherence to antihypertensive drugs in first-line therapy Abstract With obesity having doubled in the last decade, hypertension is on the rise. In one-third of hypertensive patients the metabolic syndrome is present. This might be one factor for th...
PMC12006238
core_pubmed_pmc
Pharmacokinetic Comparability and Safety Between Original and Citrate-Free Mirikizumab Formulations for Subcutaneous Injections: Results from Three Clinical Trials
Pharmacokinetic Comparability and Safety Between Original and Citrate-Free Mirikizumab Formulations for Subcutaneous Injections: Results from Three Clinical Trials Abstract Introduction Mirikizumab, a p19-directed antibody against interleukin-23 (IL-23), is administered by subcutaneous (SC) injection. Injection site pa...
PMC7466776
core_pubmed_pmc
Towards more efficient use of intravenous lumens in multi-infusion settings: development and evaluation of a multiplex infusion scheduling algorithm
Towards more efficient use of intravenous lumens in multi-infusion settings: development and evaluation of a multiplex infusion scheduling algorithm Abstract Background Multi-drug intravenous (IV) therapy is one of the most common medical procedures used in intensive care units (ICUs), operating rooms, oncology wards a...
PMC6559215
core_pubmed_pmc
Role of Physiologically Based Kinetic modelling in addressing environmental chemical mixtures – A review
Role of Physiologically Based Kinetic modelling in addressing environmental chemical mixtures – A review Abstract Highlights • The availability and applicability of Physiologically Based Kinetic (PBK) models for mixtures is reviewed. • PBK models can support risk assessment of mixtures by incorporating the toxicokineti...
PMC12001277
core_pubmed_pmc
Pharmacokinetics‐Based Design of Subcutaneous Controlled Release Systems for Biologics
Pharmacokinetics‐Based Design of Subcutaneous Controlled Release Systems for Biologics Abstract ABSTRACT Protein therapeutics have emerged as an exceedingly promising treatment modality in recent times but are predominantly given as intravenous administration. Transitioning to subcutaneous (SC) administration of these ...
PMC9175024
core_pubmed_pmc
Mechanism-Based Pharmacokinetic Model for the Deglycosylation Kinetics of 20(S)-Ginsenosides Rh2
Mechanism-Based Pharmacokinetic Model for the Deglycosylation Kinetics of 20(S)-Ginsenosides Rh2 Abstract Aim: The 20(S)-ginsenoside Rh2 (Rh2) is being developed as a new antitumor drug. However, to date, little is known about the kinetics of its deglycosylation metabolite (protopanoxadiol) (PPD) following Rh2 administ...
PMC5057355
core_pubmed_pmc
Impact of cytochrome P450 2C19 polymorphisms on the pharmacokinetics of tacrolimus when coadministered with voriconazole
Impact of cytochrome P450 2C19 polymorphisms on the pharmacokinetics of tacrolimus when coadministered with voriconazole Abstract Abstract This study evaluated the effects of cytochrome P450 (CYP) 2C19 polymorphisms on tacrolimus pharmacokinetics when coadministered with voriconazole. Eighteen healthy volunteers, inclu...
PMC6499765
core_pubmed_pmc
Modeling long-term tumor growth and kill after combinations of radiation and radiosensitizing agents
Modeling long-term tumor growth and kill after combinations of radiation and radiosensitizing agents Abstract Abstract Purpose Radiation therapy, whether given alone or in combination with chemical agents, is one of the cornerstones of oncology. We develop a quantitative model that describes tumor growth during and aft...
PMC6706129
core_pubmed_pmc
A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs
A minimally-invasive serial cerebrospinal fluid sampling model in conscious Göttingen minipigs Abstract Drug concentrations in cerebrospinal fluid (CSF) are typically used as a as a surrogate measure of their availability in the CNS, and CSF penetration in animal studies are used for assessment of CNS drug delivery in ...
PMC9747126
core_pubmed_pmc
Population pharmacokinetic/pharmacodynamic modeling of the psychedelic experience induced by N,N‐dimethyltryptamine – Implications for dose considerations
Population pharmacokinetic/pharmacodynamic modeling of the psychedelic experience induced by N,N‐dimethyltryptamine – Implications for dose considerations Abstract Abstract N,N‐dimethyltryptamine (DMT) is a psychedelic compound that is believed to have potential as a therapeutic option in several psychiatric disorders....
PMC12706889
core_pubmed_pmc
Development and evaluation of a novel nebulized dihydromyricetin formulation: enhanced pulmonary delivery and pharmacokinetic properties
Development and evaluation of a novel nebulized dihydromyricetin formulation: enhanced pulmonary delivery and pharmacokinetic properties Abstract Background Respiratory diseases are a major global health burden, and inhalation therapy offers efficient pulmonary targeting and therapeutic effectiveness. Dihydromyricetin ...
PMC10175977
core_pubmed_pmc
Population pharmacokinetics of intramuscular recombinant Erwinia chrysanthemi asparaginase (JZP458) in patients with acute lymphoblastic leukemia
Population pharmacokinetics of intramuscular recombinant Erwinia chrysanthemi asparaginase (JZP458) in patients with acute lymphoblastic leukemia Abstract Abstract JZP458 is a recombinant Erwinia chrysanthemi asparaginase for patients with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) who have develop...
PMC5131885
core_pubmed_pmc
Model‐Based Assessment of Alternative Study Designs in Pediatric Trials. Part I: Frequentist Approaches
Model‐Based Assessment of Alternative Study Designs in Pediatric Trials. Part I: Frequentist Approaches Abstract Alternative designs can increase the feasibility of pediatric trials when compared to classical parallel designs (PaD). In this work we present a model‐based approach based on clinical trial simulations for ...
PMC8286902
core_pubmed_pmc
Profile of Ipragliflozin, an Oral SGLT-2 Inhibitor for the Treatment of Type 2 Diabetes: The Evidence to Date
Profile of Ipragliflozin, an Oral SGLT-2 Inhibitor for the Treatment of Type 2 Diabetes: The Evidence to Date Abstract Abstract Background Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a novel class of pharmacotherapeutics for type 2 diabetes management that work by reducing renal reabsorption of glucose. Ipra...
PMC3205132
core_pubmed_pmc
Solid lipid nanoparticle suspension enhanced the therapeutic efficacy of praziquantel against tapeworm
Solid lipid nanoparticle suspension enhanced the therapeutic efficacy of praziquantel against tapeworm Abstract Hydatid disease caused by tapeworm is an increasing public health and socioeconomic concern. In order to enhance the therapeutic efficacy of praziquantel (PZQ) against tapeworm, PZQ-loaded hydrogenated castor...
PMC4389135
core_pubmed_pmc
Randomized trial of enteric-coated mycophenolate sodium versus mycophenolate mofetil in multi-system autoimmune disease
Randomized trial of enteric-coated mycophenolate sodium versus mycophenolate mofetil in multi-system autoimmune disease Abstract Background The use of mycophenolate mofetil (MMF) in autoimmune disease is often limited by adverse effects. In this single-centre, open label, parallel design study, we investigated whether ...
PMC6571786
core_pubmed_pmc
Drug Combinations: Mathematical Modeling and Networking Methods
Drug Combinations: Mathematical Modeling and Networking Methods Abstract Treatments consisting of mixtures of pharmacological agents have been shown to have superior effects to treatments involving single compounds. Given the vast amount of possible combinations involving multiple drugs and the restrictions in time and...
PMC7796222
core_pubmed_pmc
Pyrrolidinyl Synthetic Cathinones α-PHP and 4F-α-PVP Metabolite Profiling Using Human Hepatocyte Incubations
Pyrrolidinyl Synthetic Cathinones α-PHP and 4F-α-PVP Metabolite Profiling Using Human Hepatocyte Incubations Abstract Abstract For more than ten years, new synthetic cathinones (SCs) mimicking the effects of controlled cocaine-like stimulants have flooded the illegal drug market, causing numerous intoxications and fata...
PMC9177445
core_pubmed_pmc
Clinical pharmacokinetics of capecitabine and its metabolites in colorectal cancer patients
Clinical pharmacokinetics of capecitabine and its metabolites in colorectal cancer patients Abstract Abstract Background Capecitabine is one of the fluoropyrimidine anticancer agents which is extensively used in the management of colorectal cancer. We have noticed a discrepancy between the doses we are using in our pat...
PMC10014690
core_pubmed_pmc
First‐in‐human study of JNJ ‐63709178, a CD123 / CD3 targeting antibody, in relapsed/refractory acute myeloid leukemia
First‐in‐human study of JNJ ‐63709178, a CD123 / CD3 targeting antibody, in relapsed/refractory acute myeloid leukemia Abstract Abstract This study aimed to identify a recommended phase II dose and evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary clinical activity of JNJ‐63709178, a...
PMC9578464
core_pubmed_pmc
A technical note on emerging combination approach involved in the onconanotherapeutics
A technical note on emerging combination approach involved in the onconanotherapeutics Abstract Abstract Cancer is the second cause of mortality worldwide, and the currently available conventional treatment approach is associated with serious side effects and poor clinical outcomes. Based on the outcome of the explorat...
PMC10030934
core_pubmed_pmc
Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches
Circulating tumor DNA: Opportunities and challenges for pharmacometric approaches Abstract Abstract To support further development of model-informed drug development approaches leveraging circulating tumor DNA (ctDNA), we performed an exploratory analysis of the relationships between treatment-induced changes to ctDNA ...
PMC6875146
core_pubmed_pmc
Evolution of the EU Biosimilar Framework: Past and Future
Evolution of the EU Biosimilar Framework: Past and Future Abstract The approval of biosimilars in the EU follows a comprehensive scientific assessment based on stringent regulatory standards. While the initial approach to biosimilars was understandably cautious and conservative in that uncharted territory to protect pa...
PMC5681983
core_pubmed_pmc
Nicotine Population Pharmacokinetics in Healthy Adult Smokers: A Retrospective Analysis
Nicotine Population Pharmacokinetics in Healthy Adult Smokers: A Retrospective Analysis Abstract Abstract Background and Objective Characterizing nicotine pharmacokinetics is challenging in the presence of background exposure. We performed a combined retrospective population pharmacokinetic analysis of 8 trials, includ...
PMC7423950
core_pubmed_pmc
Metabolites profiling and pharmacokinetics of troxipide and its pharmacodynamics in rats with gastric ulcer
Metabolites profiling and pharmacokinetics of troxipide and its pharmacodynamics in rats with gastric ulcer Abstract Troxipide is widely used to treat gastric ulcer (GU) in the clinic. However, a lack of systematic metabolic, pharmacokinetic and pharmacological studies limits its clinical use. This study aimed to first...
PMC10193636
core_pubmed_pmc
An insider's perspective on FDA approval of aducanumab
An insider's perspective on FDA approval of aducanumab Abstract Abstract Introduction Aducanumab was approved in 2021 by the US Food and Drug Administration (FDA) under the accelerated approval pathway. Since then, there have been many misconceptions about the approval decision despite multiple publications from the FD...
PMC11930174
core_pubmed_pmc
A hollow fiber infection model to study intracellular and extracellular antibiotic activity against Staphylococcus aureus
A hollow fiber infection model to study intracellular and extracellular antibiotic activity against Staphylococcus aureus Abstract Summary Antibiotic activity against intracellular pathogens is commonly evaluated in static models that do not reproduce plasma concentration fluctuations. However, efficacy is influenced b...
PMC3533740
core_pubmed_pmc
Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs
Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs Abstract Based on its PK/PD ratios, doxycycline hyclate (DOX-h), a time-dependant antibacterial, is ideally expected to achieve both sustained plasma drug concentrations at or slightly above the MIC level for as long as possible be...
PMC7004040
core_pubmed_pmc
Revefenacin, a Long‐Acting Muscarinic Antagonist, Does Not Prolong QT Interval in Healthy Subjects: Results of a Placebo‐ and Positive‐Controlled Thorough QT Study
Revefenacin, a Long‐Acting Muscarinic Antagonist, Does Not Prolong QT Interval in Healthy Subjects: Results of a Placebo‐ and Positive‐Controlled Thorough QT Study Abstract Abstract Revefenacin is a novel once‐daily, lung‐selective, long‐acting muscarinic antagonist developed as a nebulized inhalation solution for the ...
PMC9368481
core_pubmed_pmc
Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development
Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development Abstract There is an urgent need for analgesics with improved efficacy, especially in neuropathic and other chronic pain conditions. Unfortunately, in recent decades, many candidate analgesics have failed in clinical phase II or III trials des...
PMC10086813
core_pubmed_pmc
Valproic acid determination by liquid chromatography coupled to mass spectrometry (LC–MS/MS) in whole blood for forensic purposes
Valproic acid determination by liquid chromatography coupled to mass spectrometry (LC–MS/MS) in whole blood for forensic purposes Abstract Abstract Valproic acid (VPA) is a well‐known drug prescribed as anti‐epileptic. It has a narrow therapeutic range and shows great individual differences in pharmacodynamics and phar...
PMC4284021
core_pubmed_pmc
Effects of the cholesteryl ester transfer protein inhibitor evacetrapib on lipoproteins, apolipoproteins and 24-h ambulatory blood pressure in healthy adults
Effects of the cholesteryl ester transfer protein inhibitor evacetrapib on lipoproteins, apolipoproteins and 24-h ambulatory blood pressure in healthy adults Abstract Abstract Objectives We investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of evacetrapib. Methods Healthy volunteers received m...
PMC9303426
core_pubmed_pmc
Transcranial magnetic stimulation as biomarker of excitability in drug development: A randomized, double‐blind, placebo‐controlled, cross‐over study
Transcranial magnetic stimulation as biomarker of excitability in drug development: A randomized, double‐blind, placebo‐controlled, cross‐over study Abstract Aims The purpose of this study was to investigate pharmacodynamic effects of drugs targeting cortical excitability using transcranial magnetic stimulation (TMS) c...
PMC8817238
core_pubmed_pmc
Proof of Concept in Assignment of Within-Subject Variability During Virtual Bioequivalence Studies: Propagation of Intra-Subject Variation in Gastrointestinal Physiology Using Physiologically Based Pharmacokinetic Modeling
Proof of Concept in Assignment of Within-Subject Variability During Virtual Bioequivalence Studies: Propagation of Intra-Subject Variation in Gastrointestinal Physiology Using Physiologically Based Pharmacokinetic Modeling Abstract While the concept of ‘Virtual Bioequivalence’ (VBE) using a combination of modelling, in...
PMC8915602
core_pubmed_pmc
Mechanistic modeling of gastrointestinal motility with integrated dissolution for simulating drug absorption
Mechanistic modeling of gastrointestinal motility with integrated dissolution for simulating drug absorption Abstract A new computational method – the multiple moving plug (MMP) model – is described to simulate the effect of gastrointestinal motility and dissolution on the pharmacokinetic profile of any given drug. The...
PMC10610279
core_pubmed_pmc
Clinical Pharmacology of Vinpocetine: Properties Revisited and Introduction of a Population Pharmacokinetic Model for Its Metabolite, Apovincaminic Acid (AVA)
Clinical Pharmacology of Vinpocetine: Properties Revisited and Introduction of a Population Pharmacokinetic Model for Its Metabolite, Apovincaminic Acid (AVA) Abstract Abstract This paper examines the use of vinpocetine in the context of clinical pharmacology. The main and active metabolite of vinpocetine is apovincami...
PMC9220236
core_pubmed_pmc
Predicting Antibiotic Effect of Vancomycin Using Pharmacokinetic/Pharmacodynamic Modeling and Simulation: Dense Sampling versus Sparse Sampling
Predicting Antibiotic Effect of Vancomycin Using Pharmacokinetic/Pharmacodynamic Modeling and Simulation: Dense Sampling versus Sparse Sampling Abstract This study aimed to investigate the effect of a structural pharmacokinetic (PK) model with fewer compartments developed following sparse sampling on the PK parameter e...
PMC4662941
core_pubmed_pmc
Trimester-Specific Population Pharmacokinetics and Other Correlates of Variability in Sulphadoxine–Pyrimethamine Disposition Among Ugandan Pregnant Women
Trimester-Specific Population Pharmacokinetics and Other Correlates of Variability in Sulphadoxine–Pyrimethamine Disposition Among Ugandan Pregnant Women Abstract Abstract Background Sulphadoxine–pyrimethamine (SP) is widely used as an intermittent preventive treatment for malaria in pregnancy (IPTp). However, pharmaco...
PMC5800559
core_pubmed_pmc
Pharmacogenomics-guided policy in opioid use disorder (OUD) management: An ethnically-diverse case-based approach ☆
Pharmacogenomics-guided policy in opioid use disorder (OUD) management: An ethnically-diverse case-based approach ☆ Abstract Abstract Introduction Opioid use disorder (OUD) is characterized by a problematic pattern of opioid use leading to clinically-significant impairment or distress. Opioid agonist treatment is an in...
PMC4420274
core_pubmed_pmc
A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01 Study)
A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01 Study) Abstract Objectives The CHARM-01 study characterized the safety, acceptability, pharmacokinetics (PK), and pharmacodynamics (PD) of three tenofovir (T...
PMC5590800
core_pubmed_pmc
Effects of Adamantyl Derivatives on Pharmacokinetic Behavior of Paclitaxel in Rats
Effects of Adamantyl Derivatives on Pharmacokinetic Behavior of Paclitaxel in Rats Abstract Paclitaxel (PTX) is one of the most frequently used anticancer agent for treating refractory ovarian cancer, metastatic breast cancer and non-small cell lung cancer. However, its oral administration is impeded by very low bioava...
PMC12680284
core_pubmed_pmc
First-in-Human, Phase I/II Dose Escalation and Expansion Study of Zelenectide Pevedotin in Patients With Advanced Solid Tumors: Results From Monotherapy Dose Escalation
First-in-Human, Phase I/II Dose Escalation and Expansion Study of Zelenectide Pevedotin in Patients With Advanced Solid Tumors: Results From Monotherapy Dose Escalation Abstract Abstract PURPOSE Zelenectide pevedotin (BT8009) is a Bicycle Drug Conjugate comprising a highly selective Nectin-4–targeting Bicycle peptide, ...
PMC8718952
core_pubmed_pmc
Assessing the impact of organ-specific lesion dynamics on survival in patients with recurrent urothelial carcinoma treated with atezolizumab or chemotherapy
Assessing the impact of organ-specific lesion dynamics on survival in patients with recurrent urothelial carcinoma treated with atezolizumab or chemotherapy Abstract Background Tumor dynamics typically rely on the sum of the longest diameters (SLD) of target lesions, and ignore heterogeneity in individual lesion dynami...
PMC5037990
core_pubmed_pmc
Generation, characterization and preclinical studies of a human anti-L1CAM monoclonal antibody that cross-reacts with rodent L1CAM
Generation, characterization and preclinical studies of a human anti-L1CAM monoclonal antibody that cross-reacts with rodent L1CAM Abstract ABSTRACT L1 cell adhesion molecule (L1CAM) is aberrantly expressed in malignant tumors and plays important roles in tumor progression. Thus, L1CAM could serve as a therapeutic targ...
PMC9771834
core_pubmed_pmc
Fighting Plasmodium chloroquine resistance with acetylenic chloroquine analogues
Fighting Plasmodium chloroquine resistance with acetylenic chloroquine analogues Abstract Malaria is among the tropical diseases that cause the most deaths in Africa. Around 500,000 malaria deaths are reported yearly among African children under the age of five. Chloroquine ( CQ ) is a low-cost antimalarial used worldw...
PMC11324678
core_pubmed_pmc
Targeting CCL24 in Inflammatory and Fibrotic Diseases: Rationale and Results from Three CM-101 Phase 1 Studies
Targeting CCL24 in Inflammatory and Fibrotic Diseases: Rationale and Results from Three CM-101 Phase 1 Studies Abstract Background Overexpression of C-C motif chemokine ligand 24 (CCL24) is associated with inflammatory and fibrotic diseases, including primary sclerosing cholangitis (PSC), systemic sclerosis, metabolic ...
PMC3142054
core_pubmed_pmc
Improved Pharmacokinetic and Pharmacodynamic Profile of Rapid-Acting Insulin Using Needle-Free Jet Injection Technology
Improved Pharmacokinetic and Pharmacodynamic Profile of Rapid-Acting Insulin Using Needle-Free Jet Injection Technology Abstract OBJECTIVE Insulin administered by jet injectors is dispensed over a larger subcutaneous area than insulin injected with a syringe, which may facilitate a more rapid absorption. This study com...
PMC12224941
core_pubmed_pmc
Sortilin‐Mediated Rapid, Precise and Sustained Degradation of Membrane Proteins via mRNA‐Encoded Lysosome‐Targeting Chimera
Sortilin‐Mediated Rapid, Precise and Sustained Degradation of Membrane Proteins via mRNA‐Encoded Lysosome‐Targeting Chimera Abstract Abstract Recent advances in lysosome‐targeting degradation technologies have introduced strategies to regulate therapeutic membrane proteins (MPs), potentially transforming treatment para...
PMC9013026
core_pubmed_pmc
Phase I study of [ 131 I] ICF01012, a targeted radionuclide therapy, in metastatic melanoma: MELRIV-1 protocol
Phase I study of [ 131 I] ICF01012, a targeted radionuclide therapy, in metastatic melanoma: MELRIV-1 protocol Abstract Background Benzamide-based radioligands targeting melanin were first developed for imaging melanoma and then for therapeutic purpose with targeted radionuclide therapy (TRT). [ 131 I]ICF01012 presents...
PMC5445231
core_pubmed_pmc
Population Pharmacokinetics of Selumetinib and Its Metabolite N‐desmethyl‐selumetinib in Adult Patients With Advanced Solid Tumors and Children With Low‐Grade Gliomas
Population Pharmacokinetics of Selumetinib and Its Metabolite N‐desmethyl‐selumetinib in Adult Patients With Advanced Solid Tumors and Children With Low‐Grade Gliomas Abstract Selumetinib (AZD6244, ARRY‐142886), a mitogen activated protein kinases (MEK1 and 2) inhibitor, has been granted orphan drug designation for dif...
PMC11762149
core_pubmed_pmc
Pharmacokinetic Analysis of an Isoniazid Suspension Among Spanish Children Under 6 Years of Age
Pharmacokinetic Analysis of an Isoniazid Suspension Among Spanish Children Under 6 Years of Age Abstract Abstract Background : Isoniazid (INH) remains a first-line drug for the treatment of tuberculosis (TB) in young children. In 2010, the WHO recommended an increase in the daily dose of INH up to 10 (7–15) mg/kg. Curr...
PMC9494154
core_pubmed_pmc
Randomized, open-label, crossover trial comparing the pharmacokinetic profile of a novel oral aspirin solution and a chewed aspirin tablet
Randomized, open-label, crossover trial comparing the pharmacokinetic profile of a novel oral aspirin solution and a chewed aspirin tablet Abstract Abstract Objectives: The primary objective of this study was to assess the pharmacokinetic profiles of acetylsalicylic acid (ASA) and salicylic acid (SA) after administrati...
PMC8206466
core_pubmed_pmc
Tyrosol as a Neuroprotector: Strong Effects of a “Weak” Antioxidant
Tyrosol as a Neuroprotector: Strong Effects of a “Weak” Antioxidant Abstract The use of neuroprotective agents for stroke is pathogenetically justified, but the translation of the results of preclinical studies of neuroprotectors into clinical practice has been a noticeable failure. One of the leading reasons for these...
PMC10986696
core_pubmed_pmc
Single-Dose Crossover Comparative Bioavailability Study of Two Different Posaconazole 100 mg Gastro-Resistant Tablets Under Fasted and Fed Conditions in Healthy Volunteers
Single-Dose Crossover Comparative Bioavailability Study of Two Different Posaconazole 100 mg Gastro-Resistant Tablets Under Fasted and Fed Conditions in Healthy Volunteers Abstract Abstract Objective This study aimed to compare the bioavailability of two different gastro-resistant oral tablet formulations of posaconazo...
PMC6689881
core_pubmed_pmc
Adverse events with fatal outcome associated with alemtuzumab treatment in multiple sclerosis
Adverse events with fatal outcome associated with alemtuzumab treatment in multiple sclerosis Abstract Abstract Objective Sporadic fatal adverse events have been reported during treatment of multiple sclerosis with alemtuzumab. To provide a systematic overview, we searched the centralized European Medicines Agency data...
PMC3203257
core_pubmed_pmc
Kinetics of the viral cycle influence pharmacodynamics of antiretroviral therapy
Kinetics of the viral cycle influence pharmacodynamics of antiretroviral therapy Abstract Abstract Background More and more antiretroviral therapies are being developed for treatment of HIV infection. The in-vivo efficacy of these drugs is commonly predicted based on in-vitro measures of antiviral effect. One primary i...
PMC12487114
core_pubmed_pmc
Single- and multiple-dose pharmacokinetics, safety, and tolerability of Aripiprazole once-monthly, long-acting intramuscular injection for Chinese adults with schizophrenia
Single- and multiple-dose pharmacokinetics, safety, and tolerability of Aripiprazole once-monthly, long-acting intramuscular injection for Chinese adults with schizophrenia Abstract Abstract Background Aripiprazole once-monthly (AOM), a long-acting injectable antipsychotic, is increasingly used in managing schizophreni...
PMC11555525
core_pubmed_pmc
The Cognitive Restoration Effects of Resveratrol: Insight Molecular through Behavioral Studies in Various Cognitive Impairment Models
The Cognitive Restoration Effects of Resveratrol: Insight Molecular through Behavioral Studies in Various Cognitive Impairment Models Abstract Cognition is essential for daily activities and progressively deteriorates with age due to various factors leading to cognitive decline. This decline often begins with memory im...
PMC10820112
core_pubmed_pmc
Animal Models in Regulatory Breakpoint Determination: Review of New Drug Applications of Approved Antibiotics from 2014–2022
Animal Models in Regulatory Breakpoint Determination: Review of New Drug Applications of Approved Antibiotics from 2014–2022 Abstract We sought to better understand the utility and role of animal models of infection for Food and Drug Administration (FDA)-approved antibiotics for the indications of community-, hospital-...
PMC5882426
core_pubmed_pmc
Optimal dose of combined rocuronium and cisatracurium during minor surgery
Optimal dose of combined rocuronium and cisatracurium during minor surgery Abstract Abstract Background: Combined rocuronium and cisatracurium have synergistic effects. We investigated whether reduced doses are effective during coadministration, by monitoring neuromuscular relaxation during surgery. Methods: This rando...
PMC6201080
core_pubmed_pmc
Randomized, Double-Blind, Placebo-Controlled Studies of the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of Eravacycline
Randomized, Double-Blind, Placebo-Controlled Studies of the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of Eravacycline Abstract Eravacycline is a novel, fully synthetic fluorocycline antibiotic with in vitro activity against aerobic and anaerobic Gram-positive and Gram-negative pathogens, includ...
PMC8541459
core_pubmed_pmc
Gentamicin Population Pharmacokinetics in Pediatric Patients—A Prospective Study with Data Analysis Using the saemix Package in R
Gentamicin Population Pharmacokinetics in Pediatric Patients—A Prospective Study with Data Analysis Using the saemix Package in R Abstract Abstract The aminoglycoside gentamicin is used for the empirical treatment of pediatric infections. It has a narrow therapeutic window. In this prospective study at University Child...
PMC11090311
core_pubmed_pmc
Validity conditions of approximations for a target-mediated drug disposition model: A novel first-order approximation and its comparison to other approximations
Validity conditions of approximations for a target-mediated drug disposition model: A novel first-order approximation and its comparison to other approximations Abstract Abstract Target-mediated drug disposition (TMDD) is a phenomenon characterized by a drug’s high-affinity binding to a target molecule, which significa...
PMC7795779
core_pubmed_pmc
Development of p -Coumaric Acid Analysis in Human Plasma and Its Clinical Application to PK/PD Study
Development of p -Coumaric Acid Analysis in Human Plasma and Its Clinical Application to PK/PD Study Abstract It has been recognized that p -Coumaric acid ( p -CA) has protective effects as an antioxidant, anti-inflammatory agent. A sensitive and efficient Liquid Chromatography-Mass Spectrometry (LC-MS) method for maxi...
PMC9095778
core_pubmed_pmc
Pharmacokinetics of XEN496, a Novel Pediatric Formulation of Ezogabine, Under Fed and Fasted Conditions: A Phase 1 Trial
Pharmacokinetics of XEN496, a Novel Pediatric Formulation of Ezogabine, Under Fed and Fasted Conditions: A Phase 1 Trial Abstract Abstract Introduction XEN496 is a novel, granular, immediate-release formulation of ezogabine intended for pediatric use. The objective of this study was to assess the effect of food on the ...
PMC10954884
core_pubmed_pmc
Moving Beyond Boundaries: Utilization of Longitudinal Exposure–Response Model for Bounded Outcome Score to Inform Decision Making in the Accelerated Drug Development Paradigm
Moving Beyond Boundaries: Utilization of Longitudinal Exposure–Response Model for Bounded Outcome Score to Inform Decision Making in the Accelerated Drug Development Paradigm Abstract Abstract Background and Objectives As drug development scientists strive to accelerate availability of therapies for patients, model-inf...
PMC11348855
core_pubmed_pmc
Innovation and optimization in autoimmune encephalitis trials: the design and rationale for the Phase 3, randomized study of satralizumab in patients with NMDAR-IgG-antibody-positive or LGI1-IgG-antibody-positive autoimmune encephalitis (CIELO)
Innovation and optimization in autoimmune encephalitis trials: the design and rationale for the Phase 3, randomized study of satralizumab in patients with NMDAR-IgG-antibody-positive or LGI1-IgG-antibody-positive autoimmune encephalitis (CIELO) Abstract Background Autoimmune encephalitis (AIE) encompasses a spectrum of...
PMC11782740
core_pubmed_pmc
Role of Dolutegravir/Lamivudine in the Management of Pregnant People Living with HIV-1: A Narrative Review
Role of Dolutegravir/Lamivudine in the Management of Pregnant People Living with HIV-1: A Narrative Review Abstract Lowering viral load during pregnancy is regarded as the most important method of reducing human immunodeficiency virus 1 (HIV-1) vertical transmission risk, and minimizing fetal exposure to drugs is a gui...
PMC9355424
core_pubmed_pmc
Five-year comparative study of thin-strut rapamycin-eluting bioabsorbable scaffold with metallic drug-eluting stent in porcine coronary artery
Five-year comparative study of thin-strut rapamycin-eluting bioabsorbable scaffold with metallic drug-eluting stent in porcine coronary artery Abstract Objectives Using quantitative coronary angiography (QCA), optical coherence tomography (OCT), histomorphometry, and pharmacokinetics, this study tried to evaluate the s...
PMC7368240
core_pubmed_pmc
Nanotechnology-Based Cisplatin Intracellular Delivery to Enhance Chemo-Sensitivity of Ovarian Cancer
Nanotechnology-Based Cisplatin Intracellular Delivery to Enhance Chemo-Sensitivity of Ovarian Cancer Abstract Abstract Background Platinum resistance is a major challenge in the management of ovarian cancer. Even low levels of acquired resistance at the cellular level lead to impaired response to cisplatin. In ovarian ...
PMC12731232
core_pubmed_pmc
Microbial Biotransformation of the Sesquiterpene Carotol: Generation of Hydroxylated Metabolites with Potential Cytotoxic and Target-Specific Binding Activities
Microbial Biotransformation of the Sesquiterpene Carotol: Generation of Hydroxylated Metabolites with Potential Cytotoxic and Target-Specific Binding Activities Abstract Carotol, the major sesquiterpene alcohol in carrot essential oil, possesses notable cytotoxic activity against various cancer cell lines, yet its meta...
PMC4940534
core_pubmed_pmc
Antimicrobial Doses in Continuous Renal Replacement Therapy: A Comparison of Dosing Strategies
Antimicrobial Doses in Continuous Renal Replacement Therapy: A Comparison of Dosing Strategies Abstract Abstract Purpose . Drug dose recommendations are not well defined in patients undergoing continuous renal replacement therapy (CRRT) due to limited published data. Several guidelines and pharmacokinetic equations hav...