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PMC12328063
core_pubmed_pmc
Optimizing Adrenaline Administration in Anaphylaxis: Clinical Practice Considerations and Safety Insights
Optimizing Adrenaline Administration in Anaphylaxis: Clinical Practice Considerations and Safety Insights Abstract ABSTRACT Background Anaphylaxis is an acute, severe, and potentially fatal reaction marked by the fast onset of symptoms and organ involvement that may lead to death from vascular collapse or airway obstru...
PMC7690341
core_pubmed_pmc
The DHODH inhibitor PTC299 arrests SARS-CoV-2 replication and suppresses induction of inflammatory cytokines
The DHODH inhibitor PTC299 arrests SARS-CoV-2 replication and suppresses induction of inflammatory cytokines Abstract Highlights • COVID-19 is typified by SARS-CoV-2 replication and an excessive inflammatory response. • PTC299 is a small orally bioavailable DHODH inhibitor that blocks pyrimidine synthesis. • PTC299 is ...
PMC12277654
core_pubmed_pmc
Population Pharmacokinetic and Pharmacokinetic‐Pharmacodynamic Modeling of Serum M‐Protein Response for Modakafusp Alfa in a Phase 1/2 Study of Patients With Relapsed or Refractory Multiple Myeloma
Population Pharmacokinetic and Pharmacokinetic‐Pharmacodynamic Modeling of Serum M‐Protein Response for Modakafusp Alfa in a Phase 1/2 Study of Patients With Relapsed or Refractory Multiple Myeloma Abstract ABSTRACT Modakafusp alfa (TAK‐573) is a novel, first‐in‐class fusion protein of a humanized anti‐CD38 IgG4 kappa ...
PMC6363138
core_pubmed_pmc
Handling Missing Dosing History in Population Pharmacokinetic Modeling: An Extension to MDM Method
Handling Missing Dosing History in Population Pharmacokinetic Modeling: An Extension to MDM Method Abstract Abstract A major challenge in population pharmacokinetic modeling is handling data with missing or potentially incorrect dosing records. Leaving such records untreated or “commented out” will cause bias in parame...
PMC8073189
core_pubmed_pmc
Quinazoline Derivatives Designed as Efflux Pump Inhibitors: Molecular Modeling and Spectroscopic Studies
Quinazoline Derivatives Designed as Efflux Pump Inhibitors: Molecular Modeling and Spectroscopic Studies Abstract Abstract Multidrug resistance of bacteria is a worrying concern in the therapeutic field and an alternative method to combat it is designing new efflux pump inhibitors (EPIs). This article presents a molecu...
PMC10552644
core_pubmed_pmc
A quantitative systems pharmacology model for certolizumab pegol treatment in moderate-to-severe psoriasis
A quantitative systems pharmacology model for certolizumab pegol treatment in moderate-to-severe psoriasis Abstract Background Psoriasis is a chronic immune-mediated inflammatory systemic disease with skin manifestations characterized by erythematous, scaly, itchy and/or painful plaques resulting from hyperproliferatio...
PMC12406653
core_pubmed_pmc
Personalized tobramycin dosing in children with cystic fibrosis: an AUC 24 -guided approach
Personalized tobramycin dosing in children with cystic fibrosis: an AUC 24 -guided approach Abstract ABSTRACT Tobramycin is commonly used for the treatment of pulmonary exacerbations in children with cystic fibrosis (CF). Currently, a standard dose of 10 mg/kg daily is used in all children. We aim to develop a populati...
PMC12386941
core_pubmed_pmc
Tuberculosis in Pregnant Women After COVID-19: Features of Prevention, Diagnosis, and Treatment (Narrative Review)
Tuberculosis in Pregnant Women After COVID-19: Features of Prevention, Diagnosis, and Treatment (Narrative Review) Abstract Abstract Tuberculosis remains a serious infectious disease that causes over 1.3 million deaths annually. Following the COVID-19 pandemic, the global incidence of tuberculosis has increased to 10.8...
PMC7042010
core_pubmed_pmc
Determination of sumatriptan in human plasma using liquid chromatography-mass spectrometry for pharmacokinetic study in healthy Korean volunteers
Determination of sumatriptan in human plasma using liquid chromatography-mass spectrometry for pharmacokinetic study in healthy Korean volunteers Abstract Abstract This study describes the development of an analytical method to determine sumatriptan levels in human plasma using high performance liquid chromatography (H...
PMC8857385
core_pubmed_pmc
Development of a Population Pharmacokinetic Model for the Diroximel Fumarate Metabolites Monomethyl Fumarate and 2-Hydroxyethyl Succinimide Following Oral Administration of Diroximel Fumarate in Healthy Participants and Patients with Multiple Sclerosis
Development of a Population Pharmacokinetic Model for the Diroximel Fumarate Metabolites Monomethyl Fumarate and 2-Hydroxyethyl Succinimide Following Oral Administration of Diroximel Fumarate in Healthy Participants and Patients with Multiple Sclerosis Abstract Introduction Diroximel fumarate (DRF) is a next-generation...
PMC7402235
core_pubmed_pmc
Molecular effects and retinopathy induced by hydroxychloroquine during SARS-CoV-2 therapy: Role of CYP450 isoforms and epigenetic modulations
Molecular effects and retinopathy induced by hydroxychloroquine during SARS-CoV-2 therapy: Role of CYP450 isoforms and epigenetic modulations Abstract Antimalaria drugs such as chloroquine (CQ) and hydroxychloroquine (HCQ) have been administered to several inflammatory diseases including rheumatoid arthritis and system...
PMC11199386
core_pubmed_pmc
Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial
Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial Abstract Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims t...
PMC11470247
core_pubmed_pmc
Association of busulfan exposure and outcomes after HCT for patients with an inborn error of immunity ∗ †
Association of busulfan exposure and outcomes after HCT for patients with an inborn error of immunity ∗ † Abstract Key Points • In patients with IEI, improved EFS and higher donor chimerism may be achieved by targeting a cumulative busulfan AUC of 80 mg × h/L. • The data stress the importance of uniformly using a valid...
PMC12641115
core_pubmed_pmc
Liposomal-synthetic-cannabidiol: preliminary translational evidence of efficacy, tolerability and pharmacokinetics following repeated subcutaneous injections in two goats
Liposomal-synthetic-cannabidiol: preliminary translational evidence of efficacy, tolerability and pharmacokinetics following repeated subcutaneous injections in two goats Abstract Cannabidiol (CBD), the primary non-psychoactive component of Cannabis sativa , has been gaining popularity as an analgesic in treatment of c...
PMC8359847
core_pubmed_pmc
Development of a physiologically based pharmacokinetic (PBPK) population model for Chinese elderly subjects
Development of a physiologically based pharmacokinetic (PBPK) population model for Chinese elderly subjects Abstract Aims This study aims to develop and verify a physiologically based pharmacokinetic (PBPK) population model for the Chinese geriatric population in Simcyp. Methods Firstly, physiological information for t...
PMC6764361
core_pubmed_pmc
Cubic and hexagonal liquid crystal gels for ocular delivery with enhanced effect of pilocarpine nitrate on anti-glaucoma treatment
Cubic and hexagonal liquid crystal gels for ocular delivery with enhanced effect of pilocarpine nitrate on anti-glaucoma treatment Abstract Abstract The objective of this work was to investigate phytantriol-based liquid crystal (LC) gels including cubic (Q 2 ) and hexagonal (H 2 ) phase for ocular delivery of pilocarpi...
PMC12637430
core_pubmed_pmc
Characterizing Variants of Uncertain Drug Resistance (VUDRs) Using Quantitative Measurements at Clinical Exposures
Characterizing Variants of Uncertain Drug Resistance (VUDRs) Using Quantitative Measurements at Clinical Exposures Abstract Abstract Somatic missense mutations in oncogenes drive resistance to anticancer drugs, yet many variants remain clinically uncharacterized. Analogous to Variants of Uncertain Significance (VUS) in...
PMC9573403
core_pubmed_pmc
Phyto-Computational Intervention of Diabetes Mellitus at Multiple Stages Using Isoeugenol from Ocimum tenuiflorum : A Combination of Pharmacokinetics and Molecular Modelling Approaches
Phyto-Computational Intervention of Diabetes Mellitus at Multiple Stages Using Isoeugenol from Ocimum tenuiflorum : A Combination of Pharmacokinetics and Molecular Modelling Approaches Abstract Abstract In the present study, the anti-diabetic potential of Ocimum tenuiflorum was investigated using computational techniqu...
PMC12072215
core_pubmed_pmc
Harnessing Open‐Source Solutions: Insights From the First Open Systems Pharmacology (OSP) Community Conference
Harnessing Open‐Source Solutions: Insights From the First Open Systems Pharmacology (OSP) Community Conference Abstract ABSTRACT In 2017, the free and open‐source software Open Systems Pharmacology (OSP) was launched. Since then, OSP has evolved from a small community into a diverse network of stakeholders committed to...
PMC12176648
core_pubmed_pmc
A B7H3-targeting antibody–drug conjugate in advanced solid tumors: a phase 1/1b trial
A B7H3-targeting antibody–drug conjugate in advanced solid tumors: a phase 1/1b trial Abstract Antibody–drug conjugates (ADCs) have emerged as a transformative modality in the treatment of solid tumors. YL201, a novel B7H3-targeting ADC, leverages a tumor microenvironment activable linker-payload platform, coupled with...
PMC5762243
core_pubmed_pmc
Quantification of tolvaptan in rabbit plasma by LC–MS/MS: Application to a pharmacokinetic study ☆
Quantification of tolvaptan in rabbit plasma by LC–MS/MS: Application to a pharmacokinetic study ☆ Abstract A sensitive, selective and high-throughput liquid chromatography–tandem mass spectrometry (LC–ESI–MS/MS) method was developed and validated for the quantitation of tolvaptan in rabbit plasma. Sample clean-up invo...
PMC9292544
core_pubmed_pmc
Bayesian modeling of a bivariate toxicity outcome for early phase oncology trials evaluating dose regimens
Bayesian modeling of a bivariate toxicity outcome for early phase oncology trials evaluating dose regimens Abstract Most phase I trials in oncology aim to find the maximum tolerated dose (MTD) based on the occurrence of dose limiting toxicities (DLT). Evaluating the schedule of administration in addition to the dose ma...
PMC12518047
core_pubmed_pmc
Evaluation of the Sedative Activity of Naringenin: In Vivo Study with Pharmacokinetics and Molecular Docking Insights
Evaluation of the Sedative Activity of Naringenin: In Vivo Study with Pharmacokinetics and Molecular Docking Insights Abstract Abstract This research is designed to investigate the sedative effects of naringenin (NAR) and diazepam against thiopental sodium‐induced sleeping mice. NAR (5 and 10 mg kg), diazepam (DZP) (2 ...
PMC7913178
core_pubmed_pmc
Population Pharmacokinetic Method to Predict Within-Subject Variability Using Single-Period Clinical Data
Population Pharmacokinetic Method to Predict Within-Subject Variability Using Single-Period Clinical Data Abstract Abstract Sample sizes for single-period clinical trials, including pharmacokinetic studies, are statistically determined by within-subject variability (WSV). However, it is difficult to determine WSV witho...
PMC5224920
core_pubmed_pmc
Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases
Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases Abstract Abstract Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear wheth...
PMC3590496
core_pubmed_pmc
P2Y 12 Receptor Inhibitors in Acute Coronary Syndromes: What Is New on the Horizon?
P2Y 12 Receptor Inhibitors in Acute Coronary Syndromes: What Is New on the Horizon? Abstract Dual antiplatelet therapy with aspirin and a P2Y 12 receptor inhibitor represents the cornerstone therapy for patients with acute coronary syndromes or undergoing percutaneous interventions, leading to a reduction of subsequent...
PMC10847206
core_pubmed_pmc
Model-Informed Precision Dosing to Reduce Vincristine-Induced Peripheral Neuropathy in Pediatric Patients: A Pharmacokinetic and Pharmacodynamic Modeling and Simulation Analysis
Model-Informed Precision Dosing to Reduce Vincristine-Induced Peripheral Neuropathy in Pediatric Patients: A Pharmacokinetic and Pharmacodynamic Modeling and Simulation Analysis Abstract Background Vincristine-induced peripheral neuropathy (VIPN) is a common adverse effect of vincristine, a drug often used in pediatric...
PMC8538292
core_pubmed_pmc
Ustekinumab Dosing Individualization in Crohn’s Disease Guided by a Population Pharmacokinetic–Pharmacodynamic Model
Ustekinumab Dosing Individualization in Crohn’s Disease Guided by a Population Pharmacokinetic–Pharmacodynamic Model Abstract Ustekinumab is a monoclonal antibody used in Crohn’s disease (CD). Dose optimization in case of non-response and the role of pharmacokinetic–pharmacodynamic (PK-PD) monitoring remain unresolved ...
PMC9412421
core_pubmed_pmc
Therapeutic Drug Monitoring of Ivacaftor, Lumacaftor, Tezacaftor, and Elexacaftor in Cystic Fibrosis: Where Are We Now?
Therapeutic Drug Monitoring of Ivacaftor, Lumacaftor, Tezacaftor, and Elexacaftor in Cystic Fibrosis: Where Are We Now? Abstract Drugs modulating the cystic fibrosis transmembrane conductance regulator (CFTR) protein, namely ivacaftor, lumacaftor, tezacaftor, and elexacaftor, are currently revolutionizing the managemen...
PMC10459228
core_pubmed_pmc
Dipeptidyl Peptidase IV Inhibitory Peptides from Chickpea Proteins ( Cicer arietinum L.): Pharmacokinetics, Molecular Interactions, and Multi-Bioactivities
Dipeptidyl Peptidase IV Inhibitory Peptides from Chickpea Proteins ( Cicer arietinum L.): Pharmacokinetics, Molecular Interactions, and Multi-Bioactivities Abstract Abstract Chickpea ( Cicer arietinum L.) peptides can inhibit dipeptidyl peptidase IV (DPP-IV), an important type 2 diabetes mellitus therapeutic target. Th...
PMC12783166
core_pubmed_pmc
Population Pharmacokinetics of Atogepant for the Prevention of Migraine
Population Pharmacokinetics of Atogepant for the Prevention of Migraine Abstract Background and Objective Atogepant is an oral calcitonin gene-related peptide receptor antagonist developed for the preventive treatment of migraine. This work aimed to develop a population pharmacokinetic (popPK) model to support dosage r...
PMC11562974
core_pubmed_pmc
Ocular Pharmacodynamics of Intravitreal Faricimab in Patients With Neovascular Age-Related Macular Degeneration or Diabetic Macular Edema
Ocular Pharmacodynamics of Intravitreal Faricimab in Patients With Neovascular Age-Related Macular Degeneration or Diabetic Macular Edema Abstract Purpose Evaluate the ocular pharmacodynamics (PD) of intravitreal faricimab, a bispecific inhibitor of angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-...
PMC9573296
core_pubmed_pmc
Variability of Isavuconazole Trough Concentrations during Longitudinal Therapeutic Drug Monitoring
Variability of Isavuconazole Trough Concentrations during Longitudinal Therapeutic Drug Monitoring Abstract Isavuconazole (ISA), a triazole antifungal agent, is licensed for the treatment of invasive aspergillosis and mucormycosis. Therapeutic drug monitoring (TDM) is a cornerstone of treatment efficacy for triazole an...
PMC4452165
core_pubmed_pmc
Enhanced antitumor effect of anti-tissue factor antibody-conjugated epirubicin-incorporating micelles in xenograft models
Enhanced antitumor effect of anti-tissue factor antibody-conjugated epirubicin-incorporating micelles in xenograft models Abstract For the creation of a successful antibody–drug conjugate (ADC), both scientific and clinical evidence has indicated that highly toxic anticancer agents (ACA) should be conjugated to a monoc...
PMC4222910
core_pubmed_pmc
In Vitro, In Silico and In Vivo Studies of Ursolic Acid as an Anti-Filarial Agent
In Vitro, In Silico and In Vivo Studies of Ursolic Acid as an Anti-Filarial Agent Abstract Abstract As part of our drug discovery program for anti-filarial agents from Indian medicinal plants, leaves of Eucalyptus tereticornis were chemically investigated, which resulted in the isolation and characterization of an anti...
PMC6519832
core_pubmed_pmc
Development of a gastroretentive delivery system for acyclovir by 3D printing technology and its in vivo pharmacokinetic evaluation in Beagle dogs
Development of a gastroretentive delivery system for acyclovir by 3D printing technology and its in vivo pharmacokinetic evaluation in Beagle dogs Abstract Abstract Gastroretentive (GR) systems are designed to prolong gastric residence time to allow sustained absorption and improve the oral bioavailability of drugs wit...
PMC8148151
core_pubmed_pmc
Considerations to Be Taken When Carrying Out Medicinal Plant Research—What We Learn from an Insight into the IC 50 Values, Bioavailability and Clinical Efficacy of Exemplary Anti-Inflammatory Herbal Components
Considerations to Be Taken When Carrying Out Medicinal Plant Research—What We Learn from an Insight into the IC 50 Values, Bioavailability and Clinical Efficacy of Exemplary Anti-Inflammatory Herbal Components Abstract Abstract Medicinal plants represent a big reservoir for discovering new drugs against all kinds of di...
PMC6915135
core_pubmed_pmc
Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution Studies
Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution Studies Abstract Abstract Brigatinib and brigatinib-analog are potent and selective ALK inhibitors with the similar structure. A simple and se...
PMC11315137
core_pubmed_pmc
Models for depression recognition and efficacy assessment based on clinical and sequencing data
Models for depression recognition and efficacy assessment based on clinical and sequencing data Abstract Major depression is a complex psychiatric disorder that includes genetic, neurological, and cognitive factors. Early detection and intervention can prevent progression, and help select the best treatment. Traditiona...
PMC12756201
core_pubmed_pmc
Pharmacokinetics, Pharmacodynamics, and Safety of ET-26 in Subjects with Mild to Moderate Renal Impairment
Pharmacokinetics, Pharmacodynamics, and Safety of ET-26 in Subjects with Mild to Moderate Renal Impairment Abstract Background and Objectives ET-26 is a novel etomidate analog with reduced adrenal suppression. This study evaluated its pharmacokinetics (PK), pharmacodynamics (PD), and safety in subjects with mild to mod...
PMC12649488
core_pubmed_pmc
Piper nigrum Extract as an Adjuvant in a Collagen System for Infected Wound Healing: Therapeutic Synergy and Biocompatibility
Piper nigrum Extract as an Adjuvant in a Collagen System for Infected Wound Healing: Therapeutic Synergy and Biocompatibility Abstract Background/Objectives : Natural plant-based compounds, especially black pepper extract, are known to have anti-inflammatory, antibacterial, and antioxidant qualities that promote procol...
PMC8612937
core_pubmed_pmc
Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)
Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS) Abstract Summary Background Sepsis is a major contributor to neonatal...
PMC6738357
core_pubmed_pmc
Amount of Cycloserine Emanating from Terizidone Metabolism and Relationship with Hepatic Function in Patients with Drug-Resistant Tuberculosis
Amount of Cycloserine Emanating from Terizidone Metabolism and Relationship with Hepatic Function in Patients with Drug-Resistant Tuberculosis Abstract Background and objectives The dosing of cycloserine and terizidone is the same, as both drugs are considered equivalent or used interchangeably. Nevertheless, it is not...
PMC3630454
core_pubmed_pmc
Population Pharmacokinetics of Intramuscular Artesunate in African Children With Severe Malaria: Implications for a Practical Dosing Regimen
Population Pharmacokinetics of Intramuscular Artesunate in African Children With Severe Malaria: Implications for a Practical Dosing Regimen Abstract Abstract Parenteral artesunate (ARS) is the drug of choice for the treatment of severe malaria. Pharmacokinetics data on intramuscular ARS are limited with respect to the...
PMC5765193
core_pubmed_pmc
Safety, pharmacokinetics and pharmacodynamics of single rising doses of BI 655064, an antagonistic anti-CD40 antibody in healthy subjects: a potential novel treatment for autoimmune diseases
Safety, pharmacokinetics and pharmacodynamics of single rising doses of BI 655064, an antagonistic anti-CD40 antibody in healthy subjects: a potential novel treatment for autoimmune diseases Abstract Abstract Purpose The CD40–CD40L pathway is a promising treatment target for autoimmune diseases such as rheumatoid arthr...
PMC9231370
core_pubmed_pmc
Therapeutic Drug Monitoring of Mycophenolic Acid as a Precision Medicine Tool for Heart Transplant Patients: Results of an Observational Pharmacokinetic Pilot Study
Therapeutic Drug Monitoring of Mycophenolic Acid as a Precision Medicine Tool for Heart Transplant Patients: Results of an Observational Pharmacokinetic Pilot Study Abstract In the clinical practice management of heart transplant (HTx), the impact of calcineurin inhibitors co-administration on pharmacokinetics (PKs) of...
PMC5877439
core_pubmed_pmc
A phase I trial of the γ-secretase inhibitor MK-0752 in combination with gemcitabine in patients with pancreatic ductal adenocarcinoma
A phase I trial of the γ-secretase inhibitor MK-0752 in combination with gemcitabine in patients with pancreatic ductal adenocarcinoma Abstract Background: The Notch pathway is frequently activated in cancer. Pathway inhibition by γ-secretase inhibitors has been shown to be effective in pre-clinical models of pancreati...
PMC8451111
core_pubmed_pmc
Exploration of the profile-effect relationship of Siraitia grosvenorii aqueous extracts related to their laxative effect on the basis of gray correlation analysis
Exploration of the profile-effect relationship of Siraitia grosvenorii aqueous extracts related to their laxative effect on the basis of gray correlation analysis Abstract Abstract Background Siraitia grosvenorii (binomial name Siraitia grosvenorii (Swingle) C. Jeffrey ex Lu et Z. Y. Zhang), also called Arhat Fruit or ...
PMC8295119
core_pubmed_pmc
Efficacy, Safety, and Immunogenicity of HLX04 Versus Reference Bevacizumab in Combination with XELOX or mFOLFOX6 as First-Line Treatment for Metastatic Colorectal Cancer: Results of a Randomized, Double-Blind Phase III Study
Efficacy, Safety, and Immunogenicity of HLX04 Versus Reference Bevacizumab in Combination with XELOX or mFOLFOX6 as First-Line Treatment for Metastatic Colorectal Cancer: Results of a Randomized, Double-Blind Phase III Study Abstract Abstract Background HLX04 is a proposed biosimilar of bevacizumab. Objective This phas...
PMC12115320
core_pubmed_pmc
Solanum macrocarpon L. Ethanolic Leaf Extract Exhibits Neuroprotective and Anxiolytic Effects in Scopolamine-Induced Amnesic Zebrafish Model
Solanum macrocarpon L. Ethanolic Leaf Extract Exhibits Neuroprotective and Anxiolytic Effects in Scopolamine-Induced Amnesic Zebrafish Model Abstract Background/Objectives : Solanum macrocarpon L. has been studied for its neuroprotective potential and memory-enhancing properties. Research suggests that bioactive compou...
PMC8450341
core_pubmed_pmc
Brief Report: Case Comparison of Therapy With the Histone Deacetylase Inhibitor Vorinostat in a Neonatal Calf Model of Pulmonary Hypertension
Brief Report: Case Comparison of Therapy With the Histone Deacetylase Inhibitor Vorinostat in a Neonatal Calf Model of Pulmonary Hypertension Abstract Pulmonary hypertension (PH) is an incurable condition in humans; driven by pulmonary vascular remodeling partially mediated by epigenetic mechanisms; and leading to righ...
PMC12771327
core_pubmed_pmc
Effects of CT-388, a once-weekly signaling-biased dual GLP-1/GIP receptor agonist, on weight loss and glycemic control in preclinical models and participants with obesity
Effects of CT-388, a once-weekly signaling-biased dual GLP-1/GIP receptor agonist, on weight loss and glycemic control in preclinical models and participants with obesity Abstract Biased agonism of the glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptors (GLP-1R/GIPR) yields greater weight los...
PMC12834180
core_pubmed_pmc
Drug–drug interactions in targeted cancer therapies: a focus on tyrosine kinase inhibitors
Drug–drug interactions in targeted cancer therapies: a focus on tyrosine kinase inhibitors Abstract Introduction: Tyrosine kinase inhibitors (TKIs) have significantly improved outcomes for cancer patients. However, TKIs have a narrow therapeutic window, impact a high-risk population, and are frequently combined with ad...
PMC12272309
core_pubmed_pmc
Exposure–Response Relationships in Patients with Non‐Small‐Cell Lung Cancer and Other Solid Tumors Treated with Patritumab Deruxtecan (HER3‐DXd)
Exposure–Response Relationships in Patients with Non‐Small‐Cell Lung Cancer and Other Solid Tumors Treated with Patritumab Deruxtecan (HER3‐DXd) Abstract Abstract Patritumab deruxtecan (HER3‐DXd, also known as MK‐1022), an antibody‐drug conjugate consisting of a human epidermal growth factor receptor 3 (HER3) antibody ...
PMC12843607
core_pubmed_pmc
Pharmacogenomics and Opioid Efficacy in Sickle Cell Disease
Pharmacogenomics and Opioid Efficacy in Sickle Cell Disease Abstract The impact of genetic variation in sickle cell patients plays a significant role in opioid therapy individual response and pain management. This review aims to provide a comprehensive overview of the importance of exploring genetic variability and its...
PMC6708437
core_pubmed_pmc
Proliposomes for oral delivery of total biflavonoids extract from Selaginella doederleinii : formulation development, optimization, and in vitro–in vivo characterization
Proliposomes for oral delivery of total biflavonoids extract from Selaginella doederleinii : formulation development, optimization, and in vitro–in vivo characterization Abstract Purpose Amentoflavone, robustaflavone, 2’’,3’’-dihydro-3’,3’’’-biapigenin, 3’,3’’’-binaringenin and delicaflavone are five major active ingre...
PMC12686112
core_pubmed_pmc
Cross-linked Chitosan-Based Shell with Mirtazapine Lipid Polymer Hybrid Core as Integrated Spray-Dried Bionanocomposites for Boosted Brain-Directed Oral Delivery
Cross-linked Chitosan-Based Shell with Mirtazapine Lipid Polymer Hybrid Core as Integrated Spray-Dried Bionanocomposites for Boosted Brain-Directed Oral Delivery Abstract Brain-directed delivery can elaborate locally to treat various brain ailments like the globally prevalent depression. Fulfilling such a goal via oral...
PMC12441310
core_pubmed_pmc
A Modeling Investigation of the CYP1A Drug Interactions of Riluzole
A Modeling Investigation of the CYP1A Drug Interactions of Riluzole Abstract ABSTRACT Cytochrome‐P‐450 (CYP)1A2 has been considered the major enzyme metabolizing riluzole since its approval. However, the inhibitor that was used in the original experiments, α‐naphthoflavone, is also a potent inhibitor of CYP1A1. In this...
PMC9971591
core_pubmed_pmc
A comprehensive overview of clinical research on dexmedetomidine in the past 2 decades: A bibliometric analysis
A comprehensive overview of clinical research on dexmedetomidine in the past 2 decades: A bibliometric analysis Abstract Introduction: Dexmedetomidine is a potent, highly selective α-2 adrenoceptor agonist with sedative, analgesic, anxiolytic, and opioid-sparing properties. A large number of dexmedetomidine-related pub...
PMC5820647
core_pubmed_pmc
Simultaneous Quantification of Gallic Acid, Bergenin, Epicatechin, Epicatechin Gallate, Isoquercitrin, and Quercetin-3-Rhamnoside in Rat Plasma by LC-MS/MS Method and Its Application to Pharmacokinetics after Oral Administration of Ardisia japonica Extract
Simultaneous Quantification of Gallic Acid, Bergenin, Epicatechin, Epicatechin Gallate, Isoquercitrin, and Quercetin-3-Rhamnoside in Rat Plasma by LC-MS/MS Method and Its Application to Pharmacokinetics after Oral Administration of Ardisia japonica Extract Abstract Ardisia japonica is a well-known traditional Chinese m...
PMC7340650
core_pubmed_pmc
Mass balance and metabolite profiling of 14 C-guadecitabine in patients with advanced cancer
Mass balance and metabolite profiling of 14 C-guadecitabine in patients with advanced cancer Abstract Summary Purpose The objective of this mass balance trial was to determine the excretory pathways and metabolic profile of the novel anticancer agent guadecitabine in humans after administration of a 14 C-radiolabeled d...
PMC12584906
core_pubmed_pmc
Therapeutic approach in the critically ill patient with suspected multidrug resistance
Therapeutic approach in the critically ill patient with suspected multidrug resistance Abstract The treatment of infections caused by multidrug-resistant microorganisms (MDROs) in critically ill patients remains a major clinical challenge due to the high mortality associated with therapeutic failure. Delays in administ...
PMC8320079
core_pubmed_pmc
Osmium Arene Germyl, Stannyl, Germanate, and Stannate Complexes as Anticancer Agents
Osmium Arene Germyl, Stannyl, Germanate, and Stannate Complexes as Anticancer Agents Abstract Abstract Herein, we describe the synthesis, full spectroscopic characterization, DFT (density functional theory) calculations, and single-crystal X-ray diffraction analyses of a series of osmium arene σ-germyl, germanate, σ-st...
PMC7762867
core_pubmed_pmc
Mechanisms of a Sustained Anti‐inflammatory Drug Response in Alveolar Macrophages Unraveled with Mathematical Modeling
Mechanisms of a Sustained Anti‐inflammatory Drug Response in Alveolar Macrophages Unraveled with Mathematical Modeling Abstract Abstract Both initiation and suppression of inflammation are hallmarks of the immune response. If not balanced, the inflammation may cause extensive tissue damage, which is associated with com...
PMC9144145
core_pubmed_pmc
Preclinical Safety and Pharmacokinetics of Heat Stable Oxytocin in Sublingual Fast-Dissolving Tablet Formulation
Preclinical Safety and Pharmacokinetics of Heat Stable Oxytocin in Sublingual Fast-Dissolving Tablet Formulation Abstract The work reported here focuses on an evaluation of a novel heat stable formulation of a uterotonic peptide drug oxytocin involving stability testing under elevated temperatures and toxicokinetic res...
PMC9520529
core_pubmed_pmc
The pharmacokinetic study of tacrolimus and Wuzhi capsule in Chinese liver transplant patients
The pharmacokinetic study of tacrolimus and Wuzhi capsule in Chinese liver transplant patients Abstract Abstract Objectives: Wuzhi Capsule (WZC) is often administrated with tacrolimus in liver transplant patients to reduce the toxicity of tacrolimus and relieve the financial burden of patients. We aimed to investigate ...
PMC8143505
core_pubmed_pmc
Application of a Physiologically Based Pharmacokinetic Model to Develop a Veterinary Amorphous Enrofloxacin Solid Dispersion
Application of a Physiologically Based Pharmacokinetic Model to Develop a Veterinary Amorphous Enrofloxacin Solid Dispersion Abstract Zoonotic intestinal pathogens threaten human health and cause huge economic losses in farming. Enrofloxacin (ENR) shows high antibacterial activity against common intestinal bacteria. Ho...
PMC9901111
core_pubmed_pmc
Antimicrobial analysis of honey against Staphylococcus aureus isolates from wound, ADMET properties of its bioactive compounds and in-silico evaluation against dihydropteroate synthase
Antimicrobial analysis of honey against Staphylococcus aureus isolates from wound, ADMET properties of its bioactive compounds and in-silico evaluation against dihydropteroate synthase Abstract Abstract Background One of the main challenges of wound healing is infection with multi-drug resistant (MDR) bacteria such as ...
PMC6555164
core_pubmed_pmc
New perspectives for reassessing fosfomycin: applicability in current clinical practice
New perspectives for reassessing fosfomycin: applicability in current clinical practice Abstract Fosfomycin is a bactericidal antibiotic that interferes with cell wall synthesis. The drug therefore has a broad spectrum of activity against a wide range of Gram-positive and Gram-negative bacteria. Both the European Medic...
PMC3517742
core_pubmed_pmc
An open prospective study of amikacin pharmacokinetics in critically ill patients during treatment with continuous venovenous haemodiafiltration
An open prospective study of amikacin pharmacokinetics in critically ill patients during treatment with continuous venovenous haemodiafiltration Abstract Background The objectives of the current study were to determine amikacin pharmacokinetics in patients undergoing treatment with continuous venovenous haemodiafiltrat...
PMC6389687
core_pubmed_pmc
Cytochrome P450 2C19 Poor Metabolizer Phenotype in Treatment Resistant Depression: Treatment and Diagnostic Implications
Cytochrome P450 2C19 Poor Metabolizer Phenotype in Treatment Resistant Depression: Treatment and Diagnostic Implications Abstract Abstract Background: Pharmacogenomic testing, specifically for pharmacokinetic (PK) and pharmacodynamic (PD) genetic variation, may contribute to a better understanding of baseline genetic d...
PMC5499344
core_pubmed_pmc
Vancomycin use, dosing and serum trough concentrations in the pediatric population: a retrospective institutional review
Vancomycin use, dosing and serum trough concentrations in the pediatric population: a retrospective institutional review Abstract Abstract Background: Vancomycin is used primarily for Gram-positive infections. Recommended dosage regimens and targeted therapeutic levels vary between institutions. Objectives: This study ...
PMC11812930
core_pubmed_pmc
Clinical study design strategies to mitigate confounding effects of time‐dependent clearance on dose optimization of therapeutic antibodies
Clinical study design strategies to mitigate confounding effects of time‐dependent clearance on dose optimization of therapeutic antibodies Abstract Abstract Time‐dependent pharmacokinetics (TDPK) is a frequent confounding factor that misleads exposure‐response (ER) analysis of therapeutic antibodies, where a decline i...
PMC12957684
core_pubmed_pmc
The role of ABC transporters in the human lung epithelium—insights from and limitations of current in vitro cell models
The role of ABC transporters in the human lung epithelium—insights from and limitations of current in vitro cell models Abstract ATP-binding cassette (ABC) drug transporter proteins are expressed at the level of the human pulmonary epithelium. This protein superfamily is known to clinically affect the pharmacokinetics ...
PMC4168390
core_pubmed_pmc
Characterizing variability in warfarin dose requirements in children using modelling and simulation
Characterizing variability in warfarin dose requirements in children using modelling and simulation Abstract Aims Although genetic, clinical and demographic factors have been shown to explain approximately half of the inter-individual variability in warfarin dose requirement in adults, less is known about causes of dos...
PMC6298197
core_pubmed_pmc
A randomized, single ascending dose study of intravenous BIIB092 in healthy participants
A randomized, single ascending dose study of intravenous BIIB092 in healthy participants Abstract Introduction Extracellular tau is hypothesized to mediate the onset and progression of tauopathies, including Alzheimer's disease, progressive supranuclear palsy, and a subset of frontotemporal lobar degenerations. A putat...
PMC5760919
core_pubmed_pmc
Liquid chromatography tandem mass spectrometry method for the estimation of lamotrigine in human plasma: Application to a pharmacokinetic study
Liquid chromatography tandem mass spectrometry method for the estimation of lamotrigine in human plasma: Application to a pharmacokinetic study Abstract A reliable, selective and sensitive liquid chromatography tandem mass spectrometry method was developed and validated for the quantification of lamotrigine in human pl...
PMC7992116
core_pubmed_pmc
Optimization, Characterization and in vivo Evaluation of Paclitaxel-Loaded Folate-Conjugated Superparamagnetic Iron Oxide Nanoparticles
Optimization, Characterization and in vivo Evaluation of Paclitaxel-Loaded Folate-Conjugated Superparamagnetic Iron Oxide Nanoparticles Abstract Abstract Background Paclitaxel (PTX) has interesting anticancer activity. However, it is insoluble in water, which seriously hinders its use in clinical. Superparamagnetic iro...
PMC3118100
core_pubmed_pmc
Population pharmacokinetics and pharmacodynamics of hydroxyurea in sickle cell anemia patients, a basis for optimizing the dosing regimen
Population pharmacokinetics and pharmacodynamics of hydroxyurea in sickle cell anemia patients, a basis for optimizing the dosing regimen Abstract Background Hydroxyurea (HU) is the first approved pharmacological treatment of sickle cell anemia (SCA). The objectives of this study were to develop population pharmacokine...
PMC9837688
core_pubmed_pmc
Sex Is the Main Determinant of Levodopa Clinical Pharmacokinetics: Evidence from a Large Series of Levodopa Therapeutic Monitoring
Sex Is the Main Determinant of Levodopa Clinical Pharmacokinetics: Evidence from a Large Series of Levodopa Therapeutic Monitoring Abstract Background: Different studies, mostly with limited cohorts, have suggested the effects of patients’ characteristics on levodopa (LD) pharmacokinetics. Objective: We primarily aimed...
PMC12115342
core_pubmed_pmc
Preparation and Evaluation of Tadalafil-Loaded Nanoemulgel for Transdermal Delivery in Cold-Induced Vasoconstriction: A Potential Therapy for Raynaud’s Phenomenon
Preparation and Evaluation of Tadalafil-Loaded Nanoemulgel for Transdermal Delivery in Cold-Induced Vasoconstriction: A Potential Therapy for Raynaud’s Phenomenon Abstract Background/Objectives: Raynaud’s phenomenon (RP) is characterized by an exaggerated vasoconstrictive response of small blood vessels in the fingers ...
PMC6222699
core_pubmed_pmc
Development of Validated Methods and Quantification of Curcuminoids and Curcumin Metabolites and Their Pharmacokinetic Study of Oral Administration of Complete Natural Turmeric Formulation (Cureit™) in Human Plasma via UPLC/ESI-Q-TOF-MS Spectrometry
Development of Validated Methods and Quantification of Curcuminoids and Curcumin Metabolites and Their Pharmacokinetic Study of Oral Administration of Complete Natural Turmeric Formulation (Cureit™) in Human Plasma via UPLC/ESI-Q-TOF-MS Spectrometry Abstract Abstract Specific and sensitive ultra-high performance liquid...
PMC11477632
core_pubmed_pmc
Exploration of Specific Fluoroquinolone Interaction with SARS-CoV-2 Main Protease (Mpro) to Battle COVID-19: DFT, Molecular Docking, ADME and Cardiotoxicity Studies
Exploration of Specific Fluoroquinolone Interaction with SARS-CoV-2 Main Protease (Mpro) to Battle COVID-19: DFT, Molecular Docking, ADME and Cardiotoxicity Studies Abstract Abstract Herein, the pharmacokinetic profiles, binding interactions, and molecular properties of fluoroquinolone derivatives as prospective antivi...
PMC8453554
core_pubmed_pmc
A Population Pharmacokinetic Meta‐Analysis of Veliparib, a PARP Inhibitor, Across Phase 1/2/3 Trials in Cancer Patients
A Population Pharmacokinetic Meta‐Analysis of Veliparib, a PARP Inhibitor, Across Phase 1/2/3 Trials in Cancer Patients Abstract Abstract Veliparib (ABT‐888) is a poly(ADP‐ribose) polymerase inhibitor in development for the treatment of high‐grade ovarian cancer or BRCA ‐mutated breast cancer in combination with carbop...
PMC9760747
core_pubmed_pmc
Sources of inter-individual variability leading to significant changes in anti-PD-1 and anti-PD-L1 efficacy identified in mouse tumor models using a QSP framework
Sources of inter-individual variability leading to significant changes in anti-PD-1 and anti-PD-L1 efficacy identified in mouse tumor models using a QSP framework Abstract Abstract While anti-PD-1 and anti-PD-L1 [anti-PD-(L)1] monotherapies are effective treatments for many types of cancer, high variability in patient ...
PMC8679590
core_pubmed_pmc
Preclinical Characterization of the Radioimmunoconjugate 111 In or 90 Y-FF-21101 Against a P-Cadherin–Expressing Tumor in a Mouse Xenograft Model and a Nonhuman Primate
Preclinical Characterization of the Radioimmunoconjugate 111 In or 90 Y-FF-21101 Against a P-Cadherin–Expressing Tumor in a Mouse Xenograft Model and a Nonhuman Primate Abstract P-cadherin is overexpressed in various cancers and can be a target for radioimmunotherapy. We investigated the preclinical pharmacokinetics an...
PMC8789466
core_pubmed_pmc
Drug Interaction between Dexamethasone and Ketoprofen with Thiopental in Male Dogs: Effect on the Recovery from Anesthesia and Pharmacokinetics Parameters
Drug Interaction between Dexamethasone and Ketoprofen with Thiopental in Male Dogs: Effect on the Recovery from Anesthesia and Pharmacokinetics Parameters Abstract Abstract Drug-drug interactions (DDIs) are an important part of clinical veterinary pharmacology. Forty-two healthy mixed breed male dogs were randomly divi...
PMC5664907
core_pubmed_pmc
The intravenous and oral pharmacokinetics of lotilaner in dogs
The intravenous and oral pharmacokinetics of lotilaner in dogs Abstract Abstract Background Lotilaner is a new oral ectoparasiticide from the isoxazoline class developed for the treatment of flea and tick infestations in dogs. It is formulated as pure S -enantiomer in flavoured chewable tablets (Credelio™). The pharmac...
PMC7354528
core_pubmed_pmc
Future Trends in Nebulized Therapies for Pulmonary Disease
Future Trends in Nebulized Therapies for Pulmonary Disease Abstract Abstract Aerosol therapy is a key modality for drug delivery to the lungs of respiratory disease patients. Aerosol therapy improves therapeutic effects by directly targeting diseased lung regions for rapid onset of action, requiring smaller doses than ...
PMC6044363
core_pubmed_pmc
Effect of green tea catechins on the pharmacokinetics of digoxin in humans
Effect of green tea catechins on the pharmacokinetics of digoxin in humans Abstract Abstract Background Previous in vitro studies have reported the inhibitory effect of green tea on p-glycoprotein (p-gp) encoded by ABCB1 . This study aimed to investigate the effect of green tea on the pharmacokinetics of digoxin, a typ...
PMC4711745
core_pubmed_pmc
Tumour-associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug
Tumour-associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug Abstract Abstract Therapeutic nanoparticles (TNPs) aim to deliver drugs more safely and effectively to cancers, yet clinical results have been unpredictable owing to limited in vivo understanding. Here we use single-cell i...
PMC12087687
core_pubmed_pmc
IQ Survey Results on Current Industry Practices—Part 1: Immunogenicity Risk Assessment
IQ Survey Results on Current Industry Practices—Part 1: Immunogenicity Risk Assessment Abstract Abstract An immunogenicity risk assessment (IRA) is a relatively new expectation of health authorities that is increasingly incorporated into the drug development process across the pharmaceutical/biotech industry. The guidi...
PMC8298375
core_pubmed_pmc
Pharmacokinetic and pharmacodynamic evaluation of nasal liposome and nanoparticle based rivastigmine formulations in acute and chronic models of Alzheimer’s disease
Pharmacokinetic and pharmacodynamic evaluation of nasal liposome and nanoparticle based rivastigmine formulations in acute and chronic models of Alzheimer’s disease Abstract Abstract With the increasing aging population and progressive nature of the disease, Alzheimer’s disease (AD) poses to be an oncoming epidemic wit...
PMC4748686
core_pubmed_pmc
Comparative pharmacokinetic evaluation and bioequivalence study of three different formulations of Imatinib Mesylate in CML patients
Comparative pharmacokinetic evaluation and bioequivalence study of three different formulations of Imatinib Mesylate in CML patients Abstract Abstract Background: Imatinib is known as the drug of choice for treatment of chronic myeloid leukemia (CML). For adults the recommended daily dosage of 400 mg requires simultane...
PMC11602527
core_pubmed_pmc
Safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral allosteric TYK2 inhibitor ESK‐001 using a randomized, double‐blind, placebo‐controlled study design
Safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral allosteric TYK2 inhibitor ESK‐001 using a randomized, double‐blind, placebo‐controlled study design Abstract Abstract ESK‐001 is a highly selective allosteric inhibitor of tyrosine kinase 2 (TYK2), which plays an essential role in mediating cytoki...
PMC4834131
core_pubmed_pmc
Systems Pharmacology Approach for Prediction of Pulmonary and Systemic Pharmacokinetics and Receptor Occupancy of Inhaled Drugs
Systems Pharmacology Approach for Prediction of Pulmonary and Systemic Pharmacokinetics and Receptor Occupancy of Inhaled Drugs Abstract Abstract Pulmonary drug disposition after inhalation is complex involving mechanisms, such as regional drug deposition, dissolution, and mucociliary clearance. This study aimed to dev...
PMC12957416
core_pubmed_pmc
Design and characterization of intravitreal bevacizumab-loaded PLGA nanoparticles: pharmacokinetic and biodistribution impact
Design and characterization of intravitreal bevacizumab-loaded PLGA nanoparticles: pharmacokinetic and biodistribution impact Abstract Abstract Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF) for treating neovascular and oncological conditions, faces challenges in biodistribution ...
PMC5190135
core_pubmed_pmc
Anticancer properties of nimbolide and pharmacokinetic considerations to accelerate its development
Anticancer properties of nimbolide and pharmacokinetic considerations to accelerate its development Abstract Abstract Nimbolide is one of the main components in the leaf extract of Azadirachta indica ( A. indica ). Accumulating evidence from various in vitro and in vivo studies indicates that nimbolide possesses potent...
PMC10191392
core_pubmed_pmc
Correlates of Myopathy in Diabetic Patients Taking Statins
Correlates of Myopathy in Diabetic Patients Taking Statins Abstract Diabetes is one of the most common chronic ailments; its incidence has reached epidemic proportions in the 21st century. Diabetes significantly increases micro and macrovascular complications, which are effectively managed with statins. Therefore, stat...
PMC11984575
core_pubmed_pmc
Humanized Na V 1.8 rats overcome cross-species potency shifts in developing novel Na V 1.8 inhibitors
Humanized Na V 1.8 rats overcome cross-species potency shifts in developing novel Na V 1.8 inhibitors Abstract Highlights • MSD199 is a potent and selective Nav1.8 inhibitor. • Humanized rats can overcome species potency shifts in developing NaV1.8 inhibitors. • MSD199 demonstrates preclinical efficacy in SNL and CFA. ...