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PMC11987044
core_pubmed_pmc
AI‐Driven Applications in Clinical Pharmacology and Translational Science: Insights From the ASCPT 2024 AI Preconference
AI‐Driven Applications in Clinical Pharmacology and Translational Science: Insights From the ASCPT 2024 AI Preconference Abstract ABSTRACT Artificial intelligence (AI) is driving innovation in clinical pharmacology and translational science with tools to advance drug development, clinical trials, and patient care. This...
PMC8703159
core_pubmed_pmc
The Pharmacokinetics of Beta-Lactam Antibiotics Using Scavenged Samples in Pediatric Intensive Care Patients: The EXPAT Kids Study Protocol
The Pharmacokinetics of Beta-Lactam Antibiotics Using Scavenged Samples in Pediatric Intensive Care Patients: The EXPAT Kids Study Protocol Abstract Abstract Background: Emerging evidence supports the importance of optimized antibiotic exposure in pediatric intensive care unit (PICU) patients. Traditional antibiotic do...
PMC9664596
core_pubmed_pmc
Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial
Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial Abstract Abstract Background Betaine is an “alternate” methyl donor for homocysteine remethylation catalyzed by betaine homocysteine methyltransferase (BHMT), an enzyme mainly expressed in the liver and kidne...
PMC5522996
core_pubmed_pmc
Big conductance calcium‐activated potassium channel openers control spasticity without sedation
Big conductance calcium‐activated potassium channel openers control spasticity without sedation Abstract Background and Purpose Our initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis (MS), whilst avoiding the sedative side effects associated with can...
PMC8192039
core_pubmed_pmc
Engineering Quick- and Long-acting Naloxone Delivery Systems for Treating Opioid Overdose
Engineering Quick- and Long-acting Naloxone Delivery Systems for Treating Opioid Overdose Abstract Abstract Purpose Opioids have been the main factor for drug overdose deaths in the United States. Current naloxone delivery systems are effective in mitigating the opioid effects only for hours. Naloxone-loaded poly(lacti...
PMC9401461
core_pubmed_pmc
Phase 1 Trial of ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Patients with Solid Tumors and Lymphomas Bearing Wild-type TP53
Phase 1 Trial of ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Patients with Solid Tumors and Lymphomas Bearing Wild-type TP53 Abstract Abstract Purpose: We describe the first-in-human dose-escalation trial for ALRN-6924, a stabilized, cell-permeating peptide that disrupts p53 inhibition by mouse double minute 2 (MD...
PMC12167921
core_pubmed_pmc
Effect of Cumulative Exposure on the Efficacy of Paroxetine: A Population Pharmacokinetic‐Pharmacodynamic and Machine Learning Analyses
Effect of Cumulative Exposure on the Efficacy of Paroxetine: A Population Pharmacokinetic‐Pharmacodynamic and Machine Learning Analyses Abstract ABSTRACT Selective serotonin reuptake inhibitors (SSRIs) are widely used in depression treatment. However, the relationship between treatment efficacy and plasma concentration...
PMC7884051
core_pubmed_pmc
“Identification of Nafamostat and VR23 as COVID-19 drug candidates by targeting 3CL pro and PL pro "
“Identification of Nafamostat and VR23 as COVID-19 drug candidates by targeting 3CL pro and PL pro " Abstract The sudden increase in the COVID-19 epidemic affected by novel coronavirus 2019 has jeopardized public health worldwide. Hence the necessities of a drug or therapeutic agent that heal SARS-CoV-2 infections are ...
PMC10835732
core_pubmed_pmc
Pharmacokinetics of Hydroxytyrosol and Its Sulfate and Glucuronide Metabolites after the Oral Administration of Table Olives to Sprague-Dawley Rats
Pharmacokinetics of Hydroxytyrosol and Its Sulfate and Glucuronide Metabolites after the Oral Administration of Table Olives to Sprague-Dawley Rats Abstract The pharmacokinetics (PK) of hydroxytyrosol and its metabolites were characterized following oral administration to Sprague-Dawley rats of 3.85 and 7.70 g of desto...
PMC7761673
core_pubmed_pmc
Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of New Anti-Migraine Drugs—Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies
Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of New Anti-Migraine Drugs—Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies Abstract Abstract In the last few years, there have been significant advances in migraine management and prevention. Lasmiditan, ubrogep...
PMC8511786
core_pubmed_pmc
Toward Predicting Impact of Common Genetic Variants on Schizophrenia Clinical Responses With Antipsychotics: A Quantitative System Pharmacology Study
Toward Predicting Impact of Common Genetic Variants on Schizophrenia Clinical Responses With Antipsychotics: A Quantitative System Pharmacology Study Abstract Abstract CNS disorders are lagging behind other indications in implementing genotype-dependent treatment algorithms for personalized medicine. This report uses a...
PMC10947261
core_pubmed_pmc
Pharmacokinetic pharmacodynamic modeling of analgesics and sedatives in children
Pharmacokinetic pharmacodynamic modeling of analgesics and sedatives in children Abstract Abstract Pharmacokinetic pharmacodynamic modeling is an important tool which uses statistical methodology to provide a better understanding of the relationship between concentration and effect of drugs such as analgesics and sedat...
PMC8121789
core_pubmed_pmc
Characterization of an engineered live bacterial therapeutic for the treatment of phenylketonuria in a human gut-on-a-chip
Characterization of an engineered live bacterial therapeutic for the treatment of phenylketonuria in a human gut-on-a-chip Abstract Engineered bacteria (synthetic biotics) represent a new class of therapeutics that leverage the tools of synthetic biology. Translational testing strategies are required to predict synthet...
PMC9147171
core_pubmed_pmc
Pharmacokinetic/Pharmacodynamic Evaluation of a New Purine-2,6-Dione Derivative in Rodents with Experimental Autoimmune Diseases
Pharmacokinetic/Pharmacodynamic Evaluation of a New Purine-2,6-Dione Derivative in Rodents with Experimental Autoimmune Diseases Abstract Current treatment strategies of autoimmune diseases (ADs) display a limited efficacy and cause numerous adverse effects. Phosphodiesterase (PDE)4 and PDE7 inhibitors have been studie...
PMC5337879
core_pubmed_pmc
Peritoneal Nebulization of Ropivacaine during Laparoscopic Cholecystectomy: Dose Finding and Pharmacokinetic Study
Peritoneal Nebulization of Ropivacaine during Laparoscopic Cholecystectomy: Dose Finding and Pharmacokinetic Study Abstract Background . Intraperitoneal nebulization of ropivacaine reduces postoperative pain and morphine consumption after laparoscopic surgery. The aim of this multicenter double-blind randomized control...
PMC8447941
core_pubmed_pmc
Synthetic Pept-Ins as a Generic Amyloid-Like Aggregation-Based Platform for In Vivo PET Imaging of Intracellular Targets
Synthetic Pept-Ins as a Generic Amyloid-Like Aggregation-Based Platform for In Vivo PET Imaging of Intracellular Targets Abstract Amyloid-like aggregation of proteins is induced by short amyloidogenic sequence segments within a specific protein sequence resulting in self-assembly into β-sheets. We recently validated a ...
PMC7725875
core_pubmed_pmc
The Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Pinostrobin in Rats: Ultra-High-Performance Liquid Chromatography Coupled With Linear Trap Quadrupole Orbitrap Mass Spectrometry Studies
The Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Pinostrobin in Rats: Ultra-High-Performance Liquid Chromatography Coupled With Linear Trap Quadrupole Orbitrap Mass Spectrometry Studies Abstract Pinostrobin is a natural flavonoid found in various plants, well known for its wide range of pharmacol...
PMC5597703
core_pubmed_pmc
Evaluation of the Population Pharmacokinetic Properties of Lidocaine and its Metabolites After Long-Term Multiple Applications of a Lidocaine Plaster in Post-Herpetic Neuralgia Patients
Evaluation of the Population Pharmacokinetic Properties of Lidocaine and its Metabolites After Long-Term Multiple Applications of a Lidocaine Plaster in Post-Herpetic Neuralgia Patients Abstract Abstract Background and Objectives Lidocaine 5% medicated plaster is the first lidocaine containing product for chronic use. ...
PMC11860008
core_pubmed_pmc
Prediction of Pharmacokinetics for CYP3A4-Metabolized Drugs in Pediatrics and Geriatrics Using Dynamic Age-Dependent Physiologically Based Pharmacokinetic Models
Prediction of Pharmacokinetics for CYP3A4-Metabolized Drugs in Pediatrics and Geriatrics Using Dynamic Age-Dependent Physiologically Based Pharmacokinetic Models Abstract Abstract Background/Objectives : The use of medicines in pediatrics and geriatrics is widespread. However, information on pharmacokinetics of therape...
PMC12156175
core_pubmed_pmc
Enhancing Oral Absorption of Quercetin Through Multifactorial Synergies in Crystal Dispersion Systems
Enhancing Oral Absorption of Quercetin Through Multifactorial Synergies in Crystal Dispersion Systems Abstract This study aims to enhance the dissolution rate and oral absorption of quercetin (QUR) by formulating quercetin crystalline solid dispersion (QUR-CSD). Quercetin, as a natural antioxidant, can effectively neut...
PMC9694406
core_pubmed_pmc
Prospective Validation and Refinement of a Population Pharmacokinetic Model of Fludarabine in Children and Young Adults Undergoing Hematopoietic Cell Transplantation
Prospective Validation and Refinement of a Population Pharmacokinetic Model of Fludarabine in Children and Young Adults Undergoing Hematopoietic Cell Transplantation Abstract Abstract Fludarabine is a nucleoside analog with antileukemic and immunosuppressive activity commonly used in allogeneic hematopoietic cell trans...
PMC12067525
core_pubmed_pmc
Effect of tripterine on the pharmacokinetics of cyclosporine A and its mechanism in rats
Effect of tripterine on the pharmacokinetics of cyclosporine A and its mechanism in rats Abstract Tripterine is a key active component in Tripterygium wilfordii polyglycosides tablets. Cyclosporine A (CsA) is an immunosuppressive drug that is widely used in organ transplantation. The combined use of Tripterygium wilfor...
PMC12196478
core_pubmed_pmc
Tissue Distribution and Pharmacokinetic Characteristics of Aztreonam Based on Multi-Species PBPK Model
Tissue Distribution and Pharmacokinetic Characteristics of Aztreonam Based on Multi-Species PBPK Model Abstract Background/Objectives : As a monocyclic β-lactam antibiotic, aztreonam has regained attention recently because combining it with β-lactamase inhibitors helps fight drug-resistant bacteria. This study aimed to...
PMC9054278
core_pubmed_pmc
A novel biocompatible, simvastatin-loaded, bone-targeting lipid nanocarrier for treating osteoporosis more effectively †
A novel biocompatible, simvastatin-loaded, bone-targeting lipid nanocarrier for treating osteoporosis more effectively † Abstract An insufficient drug concentration at the target site and drug efflux resulting in poor efficacy are recognized as important obstacles in osteoporosis treatment. Simvastatin (SIM), which can...
PMC10330959
core_pubmed_pmc
Population pharmacokinetic analysis of transdermal granisetron in healthy Chinese and Caucasian volunteers
Population pharmacokinetic analysis of transdermal granisetron in healthy Chinese and Caucasian volunteers Abstract Granisetron patches are a prolonged delivery transdermal system that is used to prevent Chemotherapy-induced nausea and vomiting (CINV). To date, no pharmacokinetics comparison between Chinese and Caucasi...
PMC10706259
core_pubmed_pmc
Pharmacokinetic Profiling of Ginsenosides, Rb1, Rd, and Rg3, in Mice with Antibiotic-Induced Gut Microbiota Alterations: Implications for Variability in the Therapeutic Efficacy of Red Ginseng Extracts
Pharmacokinetic Profiling of Ginsenosides, Rb1, Rd, and Rg3, in Mice with Antibiotic-Induced Gut Microbiota Alterations: Implications for Variability in the Therapeutic Efficacy of Red Ginseng Extracts Abstract Ginsenoside Rg3 is reported to contribute to the traditionally known diverse effects of red ginseng extracts....
PMC8468656
core_pubmed_pmc
PBPK Modeling as a Tool for Predicting and Understanding Intestinal Metabolism of Uridine 5′-Diphospho-glucuronosyltransferase Substrates
PBPK Modeling as a Tool for Predicting and Understanding Intestinal Metabolism of Uridine 5′-Diphospho-glucuronosyltransferase Substrates Abstract Uridine 5′-diphospho-glucuronosyltransferases (UGTs) are expressed in the small intestines, but prediction of first-pass extraction from the related metabolism is not well s...
PMC4869751
core_pubmed_pmc
The effect of dipyridamole on the pharmacokinetics of metformin: a randomized crossover study in healthy volunteers
The effect of dipyridamole on the pharmacokinetics of metformin: a randomized crossover study in healthy volunteers Abstract Abstract Purpose Concomitant treatment with the glucose-lowering drug metformin and the platelet aggregation inhibitor dipyridamole often occurs in patients with type 2 diabetes mellitus who have...
PMC12410251
core_pubmed_pmc
Optimizing Early Ophthalmology Clinical Trials: Home OCT and Modeling Can Reduce Sample Size by 20% to 40%
Optimizing Early Ophthalmology Clinical Trials: Home OCT and Modeling Can Reduce Sample Size by 20% to 40% Abstract Abstract Purpose Early-stage clinical trials for major retinal diseases face challenges due to substantial interpatient variability, end points with high intrapatient variability, and prolonged follow-up ...
PMC5809517
core_pubmed_pmc
Risk factors contributing to a low darunavir plasma concentration
Risk factors contributing to a low darunavir plasma concentration Abstract Abstract Darunavir is an efficacious drug; however, pharmacokinetic variability has been reported. The objective of this study was to find predisposing factors for low darunavir plasma concentrations in patients starting the once‐ or twice‐daily...
PMC11044803
core_pubmed_pmc
Improving olaparib exposure to optimize adverse effects management
Improving olaparib exposure to optimize adverse effects management Abstract Background: Olaparib is an inhibitor of the human poly-(ADP-ribose)-polymerase enzymes (PARP1/2) needed to repair single-strand DNA breaks. It is used in breast, ovarian, prostate and pancreatic cancer. Objectives: This work aimed to describe t...
PMC6536720
core_pubmed_pmc
Target identification, screening and in vivo evaluation of pyrrolone-fused benzosuberene compounds against human epilepsy using Zebrafish model of pentylenetetrazol-induced seizures
Target identification, screening and in vivo evaluation of pyrrolone-fused benzosuberene compounds against human epilepsy using Zebrafish model of pentylenetetrazol-induced seizures Abstract Pyrrolone-fused benzosuberene (PBS) compounds were semi-synthesized from α,β,γ -Himachalenes extracted from the essential oil of ...
PMC11043318
core_pubmed_pmc
Quantification of biochemical PSA dynamics after radioligand therapy with [ 177 Lu]Lu-PSMA-I&T using a population pharmacokinetic/pharmacodynamic model
Quantification of biochemical PSA dynamics after radioligand therapy with [ 177 Lu]Lu-PSMA-I&T using a population pharmacokinetic/pharmacodynamic model Abstract Abstract Background There is an unmet need for prediction of treatment outcome or patient selection for [ 177 Lu]Lu-PSMA therapy in patients with metastatic ca...
PMC7125369
core_pubmed_pmc
Safety and pharmacokinetics of Withaferin-A in advanced stage high grade osteosarcoma: A phase I trial
Safety and pharmacokinetics of Withaferin-A in advanced stage high grade osteosarcoma: A phase I trial Abstract Background Withaferin-A (WA), an active principle obtained from a traditional Indian herb known as Ashwagandha or the Indian ginseng, has been shown to prevent and cure urethane-induced lung tumors in mice, a...
PMC6263666
core_pubmed_pmc
Pharmacokinetic‐Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High‐Dose Melphalan for Autologous Stem Cell Transplant
Pharmacokinetic‐Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High‐Dose Melphalan for Autologous Stem Cell Transplant Abstract Abstract High‐dose melphalan (HDM) is part of the conditioning regimen in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT). Ho...
PMC4997947
core_pubmed_pmc
Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric Oxyhydroxide
Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric Oxyhydroxide Abstract Sucroferric oxyhydroxide (VELPHORO ® ) is a polynuclear iron-based phosphate binder recently approved for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). As a number of the available phospha...
PMC7540325
core_pubmed_pmc
The Effects of Weak and Strong CYP3A Induction by Rifampicin on the Pharmacokinetics of Five Progestins and Ethinylestradiol Compared to Midazolam
The Effects of Weak and Strong CYP3A Induction by Rifampicin on the Pharmacokinetics of Five Progestins and Ethinylestradiol Compared to Midazolam Abstract Abstract It is known that co‐administration of CYP3A inducers may decrease the effectiveness of oral contraceptives containing progestins as mono‐preparations or co...
PMC8389024
core_pubmed_pmc
Determination of Susceptibility Breakpoint for Cefquinome against Streptococcus suis in Pigs
Determination of Susceptibility Breakpoint for Cefquinome against Streptococcus suis in Pigs Abstract Streptococcus suis ( S. suis ), a zoonotic pathogen, causes severe diseases in both pigs and human beings. Cefquinome can display excellent antibacterial activity against gram-negative and gram-positive bacteria. The a...
PMC9254459
core_pubmed_pmc
A validated LC-MS/MS method for determination of antiviral prodrug molnupiravir in human plasma and its application for a pharmacokinetic modeling study in healthy Egyptian volunteers
A validated LC-MS/MS method for determination of antiviral prodrug molnupiravir in human plasma and its application for a pharmacokinetic modeling study in healthy Egyptian volunteers Abstract Abstract A fully validated, simple, rapid and reproducible liquid chromatography-tandem mass spectrometry method was developed ...
PMC4600912
core_pubmed_pmc
Comparison of Folate Receptor Targeted Optical Contrast Agents for Intraoperative Molecular Imaging
Comparison of Folate Receptor Targeted Optical Contrast Agents for Intraoperative Molecular Imaging Abstract Abstract Background . Intraoperative imaging can identify cancer cells in order to improve resection; thus fluorescent contrast agents have emerged. Our objective was to do a preclinical comparison of two fluore...
PMC4223725
core_pubmed_pmc
Evaluation of the transporter-mediated herb-drug interaction potential of DA-9801, a standardized dioscorea extract for diabetic neuropathy, in human in vitro and rat in vivo
Evaluation of the transporter-mediated herb-drug interaction potential of DA-9801, a standardized dioscorea extract for diabetic neuropathy, in human in vitro and rat in vivo Abstract Background Drug transporters play important roles in the absorption, distribution, and elimination of drugs and thereby, modulate drug e...
PMC4621644
core_pubmed_pmc
Pharmacokinetics, intestinal absorption and microbial metabolism of single platycodin D in comparison to Platycodi radix extract
Pharmacokinetics, intestinal absorption and microbial metabolism of single platycodin D in comparison to Platycodi radix extract Abstract Background: Platycodi radix , the dried root of Platycodon grandiflorum A. DC, has been widely used as food and herb medicine for treating cough, cold and other respiratory ailments,...
PMC6217653
core_pubmed_pmc
Analysis of the Binding of Aripiprazole to Human Serum Albumin: The Importance of a Chloro-Group in the Chemical Structure
Analysis of the Binding of Aripiprazole to Human Serum Albumin: The Importance of a Chloro-Group in the Chemical Structure Abstract Aripiprazole (ARP), a quinolinone derivative, is an atypical antipsychotic drug that is used in the treatment of schizophrenia. ARP has an extensive distribution and more than 99% of the A...
PMC8072969
core_pubmed_pmc
Screening of Benzimidazole-Based Anthelmintics and Their Enantiomers as Repurposed Drug Candidates in Cancer Therapy
Screening of Benzimidazole-Based Anthelmintics and Their Enantiomers as Repurposed Drug Candidates in Cancer Therapy Abstract Abstract Repurposing of approved non-antitumor drugs represents a promising and affordable strategy that may help to increase the repertoire of effective anticancer drugs. Benzimidazole-based an...
PMC11297101
core_pubmed_pmc
The many dimensions of combination therapy: How to combine antibiotics to limit resistance evolution
The many dimensions of combination therapy: How to combine antibiotics to limit resistance evolution Abstract Abstract In combination therapy, bacteria are challenged with two or more antibiotics simultaneously. Ideally, separate mutations are required to adapt to each of them, which is a priori expected to hinder the ...
PMC10976115
core_pubmed_pmc
Using an In Vivo Mouse Model to Determine the Exclusion Criteria of Preexisting Anti-AAV9 Neutralizing Antibody Titer of Pompe Disease Patients in Clinical Trials
Using an In Vivo Mouse Model to Determine the Exclusion Criteria of Preexisting Anti-AAV9 Neutralizing Antibody Titer of Pompe Disease Patients in Clinical Trials Abstract The efficacy of adeno-associated virus (AAV)-based gene therapy is dependent on effective viral transduction, which might be inhibited by preexistin...
PMC6954144
core_pubmed_pmc
Pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial
Pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial Abstract Prasugrel, a novel P2Y 12 receptor antagonist, has been shown to be more effective than clopidogrel for preventing cardiovascular events in patients with a...
PMC11133961
core_pubmed_pmc
Impact of P‐gp inhibition on systemic exposure of pralsetinib and dosing considerations
Impact of P‐gp inhibition on systemic exposure of pralsetinib and dosing considerations Abstract Abstract A study to determine the impact of cyclosporine (Neoral), an inhibitor of P‐gp, on the pharmacokinetics of pralsetinib (trade name GAVRETO ® ) was conducted in 15 healthy adult volunteers. A single 200 mg dose of p...
PMC7685239
core_pubmed_pmc
Pharmacokinetics of solifenacin in pediatric populations with overactive bladder or neurogenic detrusor overactivity
Pharmacokinetics of solifenacin in pediatric populations with overactive bladder or neurogenic detrusor overactivity Abstract Abstract The aim of this investigation was to characterize and compare the pharmacokinetics (PK) of the antimuscarinic drug solifenacin in pediatric patients with overactive bladder (OAB) or neu...
PMC11381611
core_pubmed_pmc
Study on the mechanisms and Pharmacodynamic substances of Lian-Gui-Ning-Xin-Tang on Arrhythmia Therapy based on Pharmacodynamic–Pharmacokinetic associations
Study on the mechanisms and Pharmacodynamic substances of Lian-Gui-Ning-Xin-Tang on Arrhythmia Therapy based on Pharmacodynamic–Pharmacokinetic associations Abstract Background The Chinese herbal compound Lian-Gui-Ning-Xin-Tang (LGNXT), composed of 9 herbs, has a significant antiarrhythmic effect. Previous studies have...
PMC9323915
core_pubmed_pmc
CYP3A5*3 and SLCO1B1 c.521T>C Polymorphisms Influence the Pharmacokinetics of Atorvastatin and 2-Hydroxy Atorvastatin
CYP3A5*3 and SLCO1B1 c.521T>C Polymorphisms Influence the Pharmacokinetics of Atorvastatin and 2-Hydroxy Atorvastatin Abstract Abstract There is a large variability in individual responses to atorvastatin administration. This study assessed the pharmacogenetic effects of solute carrier organic anion transporter family ...
PMC12898445
core_pubmed_pmc
Orforglipron: A Comprehensive Review of an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity and Type 2 Diabetes
Orforglipron: A Comprehensive Review of an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity and Type 2 Diabetes Abstract Abstract Orforglipron (LY3502970) is a novel, orally available, nonpeptide glucagon-like peptide-1 receptor agonist (GLP-1 RA) designed to replicate the efficacy of injectable GLP-1 RAs for gly...
PMC4538754
core_pubmed_pmc
Hepatotoxicity and pharmacokinetics of cisplatin in combination therapy with a traditional Chinese medicine compound of Zengmian Yiliu granules in ICR mice and SKOV-3-bearing nude mice
Hepatotoxicity and pharmacokinetics of cisplatin in combination therapy with a traditional Chinese medicine compound of Zengmian Yiliu granules in ICR mice and SKOV-3-bearing nude mice Abstract Abstract Background Cisplatin (CDDP) is a highly effective chemotherapeutic agent used for therapy of many tumors and has been...
PMC8813842
core_pubmed_pmc
Pharmacokinetic/Pharmacodynamic Modelling of Allopurinol, its Active Metabolite Oxypurinol, and Biomarkers Hypoxanthine, Xanthine and Uric Acid in Hypoxic-Ischemic Encephalopathy Neonates
Pharmacokinetic/Pharmacodynamic Modelling of Allopurinol, its Active Metabolite Oxypurinol, and Biomarkers Hypoxanthine, Xanthine and Uric Acid in Hypoxic-Ischemic Encephalopathy Neonates Abstract Background Allopurinol, an xanthine oxidase (XO) inhibitor, is a promising intervention that may provide neuroprotection fo...
PMC11743193
core_pubmed_pmc
Utilising paired measurements of phosphatidylethanol to monitor early success in alcohol abstinence
Utilising paired measurements of phosphatidylethanol to monitor early success in alcohol abstinence Abstract Abstract Introduction Phosphatidylethanol (PEth) is a specific and persisting marker of ethanol (alcohol) consumption. Early success of medically necessary abstinence can be assessed by monitoring PEth disappear...
PMC7540496
core_pubmed_pmc
A Phase 2, Double‐Blind, Placebo‐Controlled Trial to Investigate Potential Drug‐Drug Interactions Between Cannabidiol and Clobazam
A Phase 2, Double‐Blind, Placebo‐Controlled Trial to Investigate Potential Drug‐Drug Interactions Between Cannabidiol and Clobazam Abstract Abstract We investigated the effects of cannabidiol (CBD; 21‐day maintenance dose) on the pharmacokinetics (PK) of clobazam (CLB) and monitored the safety of CBD (or placebo) plus ...
PMC9144093
core_pubmed_pmc
Application of Machine Learning Classification to Improve the Performance of Vancomycin Therapeutic Drug Monitoring
Application of Machine Learning Classification to Improve the Performance of Vancomycin Therapeutic Drug Monitoring Abstract Bayesian therapeutic drug monitoring (TDM) software uses a reported pharmacokinetic (PK) model as prior information. Since its estimation is based on the Bayesian method, the estimation performan...
PMC12715538
core_pubmed_pmc
Physiologically Based Pharmacokinetic Modeling of Caffeine in Preterm Neonates: Influence of Renal Function and Impairment on Dosing
Physiologically Based Pharmacokinetic Modeling of Caffeine in Preterm Neonates: Influence of Renal Function and Impairment on Dosing Abstract Abstract Currently, the same weight‐based caffeine citrate dosing regimen is applied to all neonates. However, due to differences in growth trajectories by gestational age (GA) a...
PMC11876956
core_pubmed_pmc
First Results of Migoprotafib, a Potent and Highly Selective Src Homology-2 Domain–Containing Phosphatase 2 Inhibitor in Patients with Advanced Solid Tumors
First Results of Migoprotafib, a Potent and Highly Selective Src Homology-2 Domain–Containing Phosphatase 2 Inhibitor in Patients with Advanced Solid Tumors Abstract Abstract Src homology-2 domain–containing phosphatase 2 promotes rat sarcoma viral oncogene homolog–MAPK signaling and tumorigenesis and is a promising th...
PMC4788427
core_pubmed_pmc
Distinguishing Antimicrobial Models with Different Resistance Mechanisms via Population Pharmacodynamic Modeling
Distinguishing Antimicrobial Models with Different Resistance Mechanisms via Population Pharmacodynamic Modeling Abstract Abstract Semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD) modeling is increasingly used for antimicrobial drug development and optimization of dosage regimens, but systematic simulation-esti...
PMC3262315
core_pubmed_pmc
Antiplatelet therapy in acute coronary syndromes: focus on ticagrelor
Antiplatelet therapy in acute coronary syndromes: focus on ticagrelor Abstract The use of antiplatelet agents, specifically the thienopyridines, has become a standard of care in the approach to the patient presenting with an acute coronary syndrome. These drugs irreversibly inhibit the platelet by permanently binding t...
PMC7511311
core_pubmed_pmc
Visualization of the distribution of nanoparticle-formulated AZD2811 in mouse tumor model using matrix-assisted laser desorption ionization mass spectrometry imaging
Visualization of the distribution of nanoparticle-formulated AZD2811 in mouse tumor model using matrix-assisted laser desorption ionization mass spectrometry imaging Abstract Abstract Penetration of nanoparticles into viable tumor regions is essential for an effective response. Mass spectrometry imaging (MSI) is a nove...
PMC9985189
core_pubmed_pmc
Pharmacokinetics and safety of two Voriconazole formulations after intravenous infusion in two doses in healthy Chinese subjects
Pharmacokinetics and safety of two Voriconazole formulations after intravenous infusion in two doses in healthy Chinese subjects Abstract Abstract Background Voriconazole is a second-generation triazole that is used to prevent and treat invasive fungal infections. The purpose of this study was to evaluate the pharmacok...
PMC3935934
core_pubmed_pmc
Inhibition of Baicalin on Metabolism of Phenacetin, a Probe of CYP1A2, in Human Liver Microsomes and in Rats
Inhibition of Baicalin on Metabolism of Phenacetin, a Probe of CYP1A2, in Human Liver Microsomes and in Rats Abstract Baicalin has been used as mainly bioactive constituent of about 100 kinds of traditional Chinese medicines in Chinese pharmacopoeia. The effect of baicalin on cytochrome P450 should be paid more attenti...
PMC11369615
core_pubmed_pmc
Safety, Efficacy, and Biological Data of T-Cell–Enabling Oncolytic Adenovirus TILT-123 in Advanced Solid Cancers from the TUNIMO Monotherapy Phase I Trial
Safety, Efficacy, and Biological Data of T-Cell–Enabling Oncolytic Adenovirus TILT-123 in Advanced Solid Cancers from the TUNIMO Monotherapy Phase I Trial Abstract Abstract Purpose: TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with TNFa and IL2, designed to induce T-cell infiltration and cyto...
PMC12040625
core_pubmed_pmc
Structure-guided virtual screening reveals phytoconstituents as potent cathepsin B inhibitors: Implications for cancer, traumatic brain injury, and Alzheimer’s disease
Structure-guided virtual screening reveals phytoconstituents as potent cathepsin B inhibitors: Implications for cancer, traumatic brain injury, and Alzheimer’s disease Abstract Abstract Cathepsin B (CathB) is a lysosomal cysteine protease involved in various pathological and physiological processes and is becoming an a...
PMC11096781
core_pubmed_pmc
Population pharmacokinetics of intravenous daptomycin in critically ill patients: implications for selection of dosage regimens
Population pharmacokinetics of intravenous daptomycin in critically ill patients: implications for selection of dosage regimens Abstract Daptomycin is gaining prominence for the treatment of methicillin-resistant Staphylococcus aureus infections. However, the dosage selection for daptomycin in critically ill patients r...
PMC4283056
core_pubmed_pmc
Tafenoquine at therapeutic concentrations does not prolong fridericia-corrected QT interval in healthy subjects
Tafenoquine at therapeutic concentrations does not prolong fridericia-corrected QT interval in healthy subjects Abstract Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether taf...
PMC7766900
core_pubmed_pmc
Multi-Therapeutic Potential of Naringenin (4′,5,7-Trihydroxyflavonone): Experimental Evidence and Mechanisms
Multi-Therapeutic Potential of Naringenin (4′,5,7-Trihydroxyflavonone): Experimental Evidence and Mechanisms Abstract Extensive research has been carried out during the last few decades, providing a detailed account of thousands of discovered phytochemicals and their biological activities that have the potential to be ...
PMC12387821
core_pubmed_pmc
Genetic Modulation of Silodosin Exposure and Efficacy: The Role of CYP3A4, CYP3A5, and UGT2B7 Polymorphisms in Benign Prostatic Hyperplasia Management
Genetic Modulation of Silodosin Exposure and Efficacy: The Role of CYP3A4, CYP3A5, and UGT2B7 Polymorphisms in Benign Prostatic Hyperplasia Management Abstract Abstract Objectives : Silodosin, a selective α1A-adrenoceptor antagonist, is used to treat lower urinary tract symptoms (LUTS) associated with benign prostatic ...
PMC5142133
core_pubmed_pmc
Pharmacokinetic and pharmacodynamic characterization of a novel formulation containing co-formulated interferons alpha-2b and gamma in healthy male volunteers
Pharmacokinetic and pharmacodynamic characterization of a novel formulation containing co-formulated interferons alpha-2b and gamma in healthy male volunteers Abstract Background More potent antitumor activity is desired in Interferon (IFN)-treated cancer patients. This could be achieved by combining IFN alpha and IFN ...
PMC12944280
core_pubmed_pmc
Ocular and Systemic Pharmacokinetics of Baicalein and Baicalin After Intravitreal Injection and Oral Administration in Mice
Ocular and Systemic Pharmacokinetics of Baicalein and Baicalin After Intravitreal Injection and Oral Administration in Mice Abstract Abstract Background: Glaucoma requires therapies that extend beyond intraocular pressure (IOP)-lowering strategies, and baicalein (BA) offers dual IOP-lowering and neuroprotective potenti...
PMC7822507
core_pubmed_pmc
Early prognostic performance of miR155-5p monitoring for the risk of rejection: Logistic regression with a population pharmacokinetic approach in adult kidney transplant patients
Early prognostic performance of miR155-5p monitoring for the risk of rejection: Logistic regression with a population pharmacokinetic approach in adult kidney transplant patients Abstract Abstract Previous results from our group and others have shown that urinary pellet expression of miR155-5p and urinary CXCL-10 produ...
PMC8396372
core_pubmed_pmc
Multivariate Assessment for Bioequivalence Based on the Correlation of Random Effect
Multivariate Assessment for Bioequivalence Based on the Correlation of Random Effect Abstract Abstract Background and Objective Bioequivalence tests are fundamental step in assessing the equivalence in bioavailability between a test and reference product. In practice, two separate linear mixed models (LMMs) with random...
PMC5395281
core_pubmed_pmc
Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers
Bioequivalence study of a new sildenafil 100 mg orodispersible film compared to the conventional film-coated 100 mg tablet administered to healthy male volunteers Abstract A new orodispersible film formulation of the phosphodiesterase type 5 inhibitor, sildenafil, has been developed to examine the advantages of an oral...
PMC10941566
core_pubmed_pmc
Evaluation of the potential impact on pharmacokinetics of various cytochrome P450 substrates of increasing IL‐6 levels following administration of the T‐cell bispecific engager glofitamab
Evaluation of the potential impact on pharmacokinetics of various cytochrome P450 substrates of increasing IL‐6 levels following administration of the T‐cell bispecific engager glofitamab Abstract Abstract Glofitamab is a novel T cell bispecific antibody developed for treatment of relapsed‐refractory diffuse large B ce...
PMC7686313
core_pubmed_pmc
Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer
Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer Abstract Abstract Background This Phase 1 dose-escalation/expansion study assessed safety/tolerability of sapanisertib, an oral, highly selective inhibitor of mTORC1/mTOR...
PMC5572576
core_pubmed_pmc
Selective Inhibition of FLT3 by Gilteritinib in Relapsed/Refractory Acute Myeloid Leukemia: a Multicenter, First-in-human, Open-label, Phase 1/2 Study
Selective Inhibition of FLT3 by Gilteritinib in Relapsed/Refractory Acute Myeloid Leukemia: a Multicenter, First-in-human, Open-label, Phase 1/2 Study Abstract Abstract Background Fms -like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations are common in acute myeloid leukemia (AML) and are associated w...
PMC9785299
core_pubmed_pmc
Applications of In Silico Models to Predict Drug-Induced Liver Injury
Applications of In Silico Models to Predict Drug-Induced Liver Injury Abstract Abstract Drug-induced liver injury (DILI) is a major cause of the withdrawal of pre-marketed drugs, typically attributed to oxidative stress, mitochondrial damage, disrupted bile acid homeostasis, and innate immune-related inflammation. DILI...
PMC12503347
core_pubmed_pmc
SNP genotypes in CYP2C9 and VKORC1 genes do not affect prostate cancer or cancer mortality among warfarin users in Finnish prostate cancer patients
SNP genotypes in CYP2C9 and VKORC1 genes do not affect prostate cancer or cancer mortality among warfarin users in Finnish prostate cancer patients Abstract Abstract The coagulation cascade is thought to contribute to cancer progression. Although in vitro studies suggest that anticoagulants, such as warfarin, might red...
PMC10135263
core_pubmed_pmc
Comparison of Intravenous Microdialysis and Standard Plasma Sampling for Monitoring of Vancomycin and Meropenem Plasma Concentrations—An Experimental Porcine Study
Comparison of Intravenous Microdialysis and Standard Plasma Sampling for Monitoring of Vancomycin and Meropenem Plasma Concentrations—An Experimental Porcine Study Abstract Abstract Microdialysis is a catheter-based method suitable for dynamic sampling of unbound antibiotic concentrations. Intravenous antibiotic concen...
PMC11871726
core_pubmed_pmc
In vitro activity of rifampicin, rifapentine and rifabutin in combination with their 25-deacetyl-metabolites against various Mycobacterium tuberculosis lineages
In vitro activity of rifampicin, rifapentine and rifabutin in combination with their 25-deacetyl-metabolites against various Mycobacterium tuberculosis lineages Abstract Objectives Rifamycin agents (rifampicin (RIF), rifapentine (RFP), rifabutin (RFB)) are the cornerstone of tuberculosis (TB) therapy. Rifamycins are me...
PMC10833183
core_pubmed_pmc
Relevance of pharmacogenetic analyses and therapeutic drug monitoring of antidepressants for an individualized treatment of peripartum psychopathology
Relevance of pharmacogenetic analyses and therapeutic drug monitoring of antidepressants for an individualized treatment of peripartum psychopathology Abstract Objective Psychiatric disorders burden the peripartum period, often requiring psychopharmacological treatment, including antidepressants. Efficacy and tolerabil...
PMC12240381
core_pubmed_pmc
Computational insights into flavonoids inhibition of dengue virus envelope protein: ADMET profiling, molecular docking, dynamics, PCA, and end-state free energy calculations
Computational insights into flavonoids inhibition of dengue virus envelope protein: ADMET profiling, molecular docking, dynamics, PCA, and end-state free energy calculations Abstract Abstract Dengue virus is a critical worldwide health concern, and efforts to identify useful antiviral drugs remain imperative. This stud...
PMC10363032
core_pubmed_pmc
Phase I study to assess the effect of adavosertib (AZD1775) on the pharmacokinetics of substrates of CYP1A2, CYP2C19, and CYP3A in patients with advanced solid tumors
Phase I study to assess the effect of adavosertib (AZD1775) on the pharmacokinetics of substrates of CYP1A2, CYP2C19, and CYP3A in patients with advanced solid tumors Abstract Abstract Purpose Adavosertib may alter exposure to substrates of the cytochrome P450 (CYP) family of enzymes. This study assessed its effect on ...
PMC3570572
core_pubmed_pmc
Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications
Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications Abstract Abstract Cannabis is one of the most widely abused substances throughout the world. The primary psychoactive constituent of cannabis, delta 9-tetrahydrocannabinol (▵ 9_ THC), produces a myriad of pharmacological effects in animals and hum...
PMC3137796
core_pubmed_pmc
Cassia auriculata : Aspects of Safety Pharmacology and Drug Interaction
Cassia auriculata : Aspects of Safety Pharmacology and Drug Interaction Abstract Abstract Safety pharmacology studies help in identifying preclinical adverse drug reactions. We carried out routine safety pharmacology with focus on cardiovascular variables and pharmacokinetic herb-drug interaction studies on rats fed wi...
PMC4314250
core_pubmed_pmc
Evaluating Health Risks from Inhaled Polychlorinated Biphenyls: Research Needs for Addressing Uncertainty
Evaluating Health Risks from Inhaled Polychlorinated Biphenyls: Research Needs for Addressing Uncertainty Abstract Background: Indoor air concentrations of polychlorinated biphenyls (PCBs) in some buildings are one or more orders of magnitude higher than background levels. In response to this, efforts have been made to...
PMC6353801
core_pubmed_pmc
Enhanced Anti-diabetic Effect of Berberine Combined With Timosaponin B2 in Goto-Kakizaki Rats, Associated With Increased Variety and Exposure of Effective Substances Through Intestinal Absorption
Enhanced Anti-diabetic Effect of Berberine Combined With Timosaponin B2 in Goto-Kakizaki Rats, Associated With Increased Variety and Exposure of Effective Substances Through Intestinal Absorption Abstract Objective: Inspired by the traditionally clinical application of herb pair Zhimu - Huangbo to treat diabetes, a com...
PMC8449932
core_pubmed_pmc
Immunogenicity to biological drugs in psoriasis and psoriatic arthritis
Immunogenicity to biological drugs in psoriasis and psoriatic arthritis Abstract Monoclonal antibodies or fusion proteins, defined as biological drugs, have modified the natural history of numerous immune-mediated disorders, allowing the development of therapies aimed at blocking the pathophysiological pathways of the ...
PMC9921301
core_pubmed_pmc
Design, Synthesis, and Antiproliferative Activity of New 5-Chloro-indole-2-carboxylate and Pyrrolo[3,4- b ]indol-3-one Derivatives as Potent Inhibitors of EGFR T790M /BRAF V600E Pathways
Design, Synthesis, and Antiproliferative Activity of New 5-Chloro-indole-2-carboxylate and Pyrrolo[3,4- b ]indol-3-one Derivatives as Potent Inhibitors of EGFR T790M /BRAF V600E Pathways Abstract Abstract Mutant EGFR/BRAF pathways are thought to be crucial targets for the development of anticancer drugs since they are ...
PMC6973126
core_pubmed_pmc
Preferential Inhibition of JAK1 Relative to JAK3 by Upadacitinib: Exposure‐Response Analyses of Ex Vivo Data From 2 Phase 1 Clinical Trials and Comparison to Tofacitinib
Preferential Inhibition of JAK1 Relative to JAK3 by Upadacitinib: Exposure‐Response Analyses of Ex Vivo Data From 2 Phase 1 Clinical Trials and Comparison to Tofacitinib Abstract Abstract Upadacitinib is a selective Janus kinase (JAK) 1 inhibitor being developed for treatment of rheumatoid arthritis. This study charact...
PMC3684141
core_pubmed_pmc
Differential effects of dosing regimen on the safety and efficacy of dasatinib: retrospective exposure–response analysis of a Phase III study
Differential effects of dosing regimen on the safety and efficacy of dasatinib: retrospective exposure–response analysis of a Phase III study Abstract Abstract Purpose Dasatinib is a prototypic short half-life BCR-ABL1 tyrosine kinase inhibitor. The recommended dose of dasatinib for chronic myeloid leukemia in chronic ...
PMC4342742
core_pubmed_pmc
Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model
Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model Abstract Abstract The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxi...
PMC11342882
core_pubmed_pmc
Modulation of the pharmacokinetics of soluble ACE2 decoy receptors through glycosylation
Modulation of the pharmacokinetics of soluble ACE2 decoy receptors through glycosylation Abstract The Spike of SARS-CoV-2 recognizes a transmembrane protease, angiotensin-converting enzyme 2 (ACE2), on host cells to initiate infection. Soluble derivatives of ACE2, in which Spike affinity is enhanced and the protein is ...
PMC12908643
core_pubmed_pmc
Efficacy and Safety of Aficamten in Children and Adolescents With Obstructive Hypertrophic Cardiomyopathy: Study Design and Rationale of CEDAR-HCM
Efficacy and Safety of Aficamten in Children and Adolescents With Obstructive Hypertrophic Cardiomyopathy: Study Design and Rationale of CEDAR-HCM Abstract BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality in children, but treatment options are limited. Aficamten, a next-in-...
PMC10676574
core_pubmed_pmc
In-silico and in-vitro screening of Asiatic acid and Asiaticoside A against Cathepsin S enzyme
In-silico and in-vitro screening of Asiatic acid and Asiaticoside A against Cathepsin S enzyme Abstract Abstract Background Atherosclerosis is a form of cardiovascular disease that affects the endothelium of the blood vessel. Series of events are involved in the pathophysiology of this disease which includes the breaki...
PMC9959474
core_pubmed_pmc
Nanosystems for Brain Targeting of Antipsychotic Drugs: An Update on the Most Promising Nanocarriers for Increased Bioavailability and Therapeutic Efficacy
Nanosystems for Brain Targeting of Antipsychotic Drugs: An Update on the Most Promising Nanocarriers for Increased Bioavailability and Therapeutic Efficacy Abstract Abstract Orally administered antipsychotic drugs are the first-line treatment for psychotic disorders, such as schizophrenia and bipolar disorder. Neverthe...
PMC8012855
core_pubmed_pmc
Design and High Expression of Non-glycosylated Lysostaphins in Pichia pastoris and Their Pharmacodynamic Study
Design and High Expression of Non-glycosylated Lysostaphins in Pichia pastoris and Their Pharmacodynamic Study Abstract Abstract Lysostaphin is an effective antimicrobial agent to Staphylococcus , especially for the methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Staphylococcus aureus (MDRSA)...
PMC5024067
core_pubmed_pmc
Safety, tolerability, and pharmacokinetics of SMT C1100, a 2‐arylbenzoxazole utrophin modulator, following single‐ and multiple‐dose administration to healthy male adult volunteers
Safety, tolerability, and pharmacokinetics of SMT C1100, a 2‐arylbenzoxazole utrophin modulator, following single‐ and multiple‐dose administration to healthy male adult volunteers Abstract Abstract SMT C1100 is a small molecule utrophin modulator in development to treat Duchenne muscular dystrophy. This study evaluate...