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PMC3615930
core_pubmed_pmc
Effect of verapamil on systemic exposure and safety of umeclidinium and vilanterol: a randomized and open-label study
Effect of verapamil on systemic exposure and safety of umeclidinium and vilanterol: a randomized and open-label study Abstract Abstract Background The combination of umeclidinium (UMEC), a long-acting muscarinic receptor antagonist, and vilanterol (VI), a selective long-acting β 2 agonist, is in development for the tre...
PMC5647335
core_pubmed_pmc
Controlling the bioactivity of a peptide hormone in vivo by reversible self-assembly
Controlling the bioactivity of a peptide hormone in vivo by reversible self-assembly Abstract The use of peptides as therapeutic agents is undergoing a renaissance with the expectation of new drugs with enhanced levels of efficacy and safety. Their clinical potential will be only fully realised once their physicochemic...
PMC10981579
core_pubmed_pmc
Ezabenlimab (BI 754091), an anti-PD-1 antibody, in patients with advanced solid tumours
Ezabenlimab (BI 754091), an anti-PD-1 antibody, in patients with advanced solid tumours Abstract Abstract Background Ezabenlimab (BI 754091) is a humanised monoclonal antibody targeting programmed cell death protein-1. We report results from open-label, dose-escalation/expansion, Phase I trials that evaluated the safet...
PMC5914018
core_pubmed_pmc
N-of-1 trials in the clinical care of patients in developing countries: a systematic review
N-of-1 trials in the clinical care of patients in developing countries: a systematic review Abstract Abstract Background N-of-1 trials have a potential role in promoting patient-centered medicine in developing countries. However, there is limited academic literature regarding the use of N-of-1 trials in the clinical ca...
PMC9579398
core_pubmed_pmc
A proof of concept using the Ussing chamber methodology to study pediatric intestinal drug transport and age‐dependent differences in absorption
A proof of concept using the Ussing chamber methodology to study pediatric intestinal drug transport and age‐dependent differences in absorption Abstract Abstract Little is known about the impact of age on the processes governing human intestinal drug absorption. The Ussing chamber is a system to study drug transport a...
PMC7654938
core_pubmed_pmc
Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules
Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules Abstract Objective IPX203 is an investigational oral extended-release capsule formulation of carbidopa-lev...
PMC5075098
core_pubmed_pmc
Preclinical Evaluation of the Stability, Safety, and Efficacy of CD101, a Novel Echinocandin
Preclinical Evaluation of the Stability, Safety, and Efficacy of CD101, a Novel Echinocandin Abstract Abstract Fungal infections pose a significant public health burden with high morbidity and mortality. CD101 is a novel echinocandin under development for the treatment and prevention of systemic Candida infections. Pre...
PMC7032964
core_pubmed_pmc
Treatment response and disease progression
Treatment response and disease progression Abstract Abstract This tutorial defines the concepts of disease progression in the context of clinical pharmacology. Disease progression describes the natural history of disease, such as pain, or biomarker of drug response, such as blood pressure. The action of a drug, such as...
PMC11891907
core_pubmed_pmc
Nanomedicine Innovations for Lung Cancer Diagnosis and Therapy
Nanomedicine Innovations for Lung Cancer Diagnosis and Therapy Abstract Lung cancer remains a challenge within the realm of oncology. Characterized by late-stage diagnosis and resistance to conventional treatments, the currently available therapeutic strategies encompass surgery, radiotherapy, chemotherapy, immunothera...
PMC12678371
core_pubmed_pmc
Preclinical pharmacokinetic characterization of (R)-ketamine injection, a novel antidepressant glutamatergic agent
Preclinical pharmacokinetic characterization of (R)-ketamine injection, a novel antidepressant glutamatergic agent Abstract Introduction Ketamine is a significant class of antidepressant drugs, and the pharmacokinetic and pharmacodynamic characteristics of its enantiomers exhibit differences. Among them, intravenous in...
PMC5221883
core_pubmed_pmc
Pharmacokinetics of Lidocaine Hydrochloride Administered with or without Adrenaline for the Paravertebral Brachial Plexus Block in Dogs
Pharmacokinetics of Lidocaine Hydrochloride Administered with or without Adrenaline for the Paravertebral Brachial Plexus Block in Dogs Abstract Adrenaline is known to prolong the duration of local anesthesia but its effects on the pharmacokinetic processes of local anesthetic drugs are not fully understood. Our object...
PMC7867377
core_pubmed_pmc
Phytochemistry, Bioactivities, Pharmacokinetics and Toxicity Prediction of Selaginella repanda with Its Anticancer Potential against Human Lung, Breast and Colorectal Carcinoma Cell Lines
Phytochemistry, Bioactivities, Pharmacokinetics and Toxicity Prediction of Selaginella repanda with Its Anticancer Potential against Human Lung, Breast and Colorectal Carcinoma Cell Lines Abstract In this study, we investigated the bioactive potential (antibacterial and antioxidant), anticancer activity and detailed ph...
PMC6224495
core_pubmed_pmc
Localising functionalised gold-nanoparticles in murine spinal cords by X-ray fluorescence imaging and background-reduction through spatial filtering for human-sized objects
Localising functionalised gold-nanoparticles in murine spinal cords by X-ray fluorescence imaging and background-reduction through spatial filtering for human-sized objects Abstract Accurate in vivo localisation of minimal amounts of functionalised gold-nanoparticles, enabling e.g . early-tumour diagnostics and pharmac...
PMC5651340
core_pubmed_pmc
First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer's disease
First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer's disease Abstract Introduction Aducanumab (BIIB037), a human monoclonal antibody selective for aggregated forms of amyloid beta, is being investigated as a disease-modifying treatment fo...
PMC11835422
core_pubmed_pmc
Clinical and Physiologically Based Pharmacokinetic Model Evaluations of Adagrasib Drug–Drug Interactions
Clinical and Physiologically Based Pharmacokinetic Model Evaluations of Adagrasib Drug–Drug Interactions Abstract Abstract Adagrasib is a potent, highly selective, orally available, small molecule, covalent inhibitor of G12C mutated KRAS. As both a substrate and strong inhibitor of cytochrome P450 (CYP) 3A4, adagrasib ...
PMC9017385
core_pubmed_pmc
Pharmacokinetics of Temsavir, the Active Moiety of the HIV-1 Attachment Inhibitor Prodrug, Fostemsavir, Coadministered with Cobicistat, Etravirine, Darunavir/Cobicistat, or Darunavir/Ritonavir with or without Etravirine in Healthy Participants
Pharmacokinetics of Temsavir, the Active Moiety of the HIV-1 Attachment Inhibitor Prodrug, Fostemsavir, Coadministered with Cobicistat, Etravirine, Darunavir/Cobicistat, or Darunavir/Ritonavir with or without Etravirine in Healthy Participants Abstract ABSTRACT Fostemsavir is a prodrug of temsavir, a first-in-class att...
PMC9090854
core_pubmed_pmc
Predicting Viable Skin Concentration: Modelling the Subpapillary Plexus
Predicting Viable Skin Concentration: Modelling the Subpapillary Plexus Abstract Abstract The skin concentration of a substance after a topical application or exposure determines both local treatment outcomes and the dermal toxicity assessment of various products. However, quantifying the time course of those concentra...
PMC10439066
core_pubmed_pmc
Hepatotoxicity of AKR1C3 Inhibitor BAY1128688: Findings from an Early Terminated Phase IIa Trial for the Treatment of Endometriosis
Hepatotoxicity of AKR1C3 Inhibitor BAY1128688: Findings from an Early Terminated Phase IIa Trial for the Treatment of Endometriosis Abstract Introduction BAY1128688 is a selective inhibitor of aldo-keto reductase family 1 member C3 (AKR1C3), an enzyme implicated in the pathology of endometriosis and other disorders. In...
PMC6951463
core_pubmed_pmc
Population Pharmacokinetic/Pharmacodynamic Analysis of Intravenous Zanamivir in Healthy Adults and Hospitalized Adult and Pediatric Subjects With Influenza
Population Pharmacokinetic/Pharmacodynamic Analysis of Intravenous Zanamivir in Healthy Adults and Hospitalized Adult and Pediatric Subjects With Influenza Abstract Abstract Zanamivir is a potent and highly selective inhibitor of influenza neuraminidase in which the inhibition of this enzyme prevents the virus from inf...
PMC12625128
core_pubmed_pmc
A model‐informed clinical trial simulation tool with a graphical user interface for Duchenne muscular dystrophy
A model‐informed clinical trial simulation tool with a graphical user interface for Duchenne muscular dystrophy Abstract Abstract Quantitative model‐based clinical trial simulation tools play a critical role in informing study designs through simulation before actual execution. These tools help drug developers explore ...
PMC8100460
core_pubmed_pmc
CYP3A5 and UGT1A9 Polymorphisms Influence Immunosuppressive Therapy in Pediatric Kidney Transplant Recipients
CYP3A5 and UGT1A9 Polymorphisms Influence Immunosuppressive Therapy in Pediatric Kidney Transplant Recipients Abstract Abstract Background: Tacrolimus (TAC) and mycophenolic acid (MPA) are the main immunosuppressive drugs used in pediatric kidney transplantation. Single nucleotide polymorphisms (SNPs) in metabolizing e...
PMC9102399
core_pubmed_pmc
Comparative Study of Preparation, Evaluation, and Pharmacokinetics in Beagle Dogs of Curcumin β-Cyclodextrin Inclusion Complex, Curcumin Solid Dispersion, and Curcumin Phospholipid Complex
Comparative Study of Preparation, Evaluation, and Pharmacokinetics in Beagle Dogs of Curcumin β-Cyclodextrin Inclusion Complex, Curcumin Solid Dispersion, and Curcumin Phospholipid Complex Abstract Curcumin is a natural acidic polyphenol extracted from turmeric with a wide range of biological and pharmacological effect...
PMC10209603
core_pubmed_pmc
Pharmacokinetics and effect of maslinic acid with physical exercise on grip strength and trunk muscle mass in healthy Japanese individuals
Pharmacokinetics and effect of maslinic acid with physical exercise on grip strength and trunk muscle mass in healthy Japanese individuals Abstract Abstract Age-related changes in physical function are closely associated with daily activity impairment among the elderly. Continuous maslinic acid intake may improve skele...
PMC7044683
core_pubmed_pmc
United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts
United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts Abstract Abstract As part of the United States Pharmacopeia’s ongoing review of dietary supplement safety data, a new comprehensive systematic review on green tea extracts (GTE) has been completed. GTEs may contain hepatot...
PMC6934983
core_pubmed_pmc
A New Model to Describe the Single-dose Pharmacokinetics of Bevacizumab and Predict Its Multiple-Dose Pharmacokinetics in Beagle Dogs
A New Model to Describe the Single-dose Pharmacokinetics of Bevacizumab and Predict Its Multiple-Dose Pharmacokinetics in Beagle Dogs Abstract Abstract Complex pharmacokinetic (PK) properties including nonlinear elimination were encountered by some monoclonal antibodies (mAbs), and classic compartment models sometimes ...
PMC8128043
core_pubmed_pmc
Pharmacokinetics and pharmacodynamics in the treatment of cutaneous leishmaniasis – challenges and opportunities
Pharmacokinetics and pharmacodynamics in the treatment of cutaneous leishmaniasis – challenges and opportunities Abstract Pharmacological efficacy is obtained when adequate concentrations of a potent drug reach the target site. In cutaneous leishmaniasis, a heterogeneous disease characterised by a variety of skin manif...
PMC9909811
core_pubmed_pmc
In Silico Characterization of Withania coagulans Bioactive Compounds as Potential Inhibitors of Hydroxymethylglutaryl (HMG-CoA) Reductase of Mus musculus
In Silico Characterization of Withania coagulans Bioactive Compounds as Potential Inhibitors of Hydroxymethylglutaryl (HMG-CoA) Reductase of Mus musculus Abstract Abstract Hypercholesterolemia is a mediator for the etiology of cardiovascular diseases, which are characterized as the global leading cause of mortality. We...
PMC10982099
core_pubmed_pmc
Explaining in-vitro to in-vivo efficacy correlations in oncology pre-clinical development via a semi-mechanistic mathematical model
Explaining in-vitro to in-vivo efficacy correlations in oncology pre-clinical development via a semi-mechanistic mathematical model Abstract Abstract In-vitro to in-vivo correlations (IVIVC), relating in-vitro parameters like IC 50 to in-vivo drug exposure in plasma and tumour growth, are widely used in oncology for ex...
PMC10269516
core_pubmed_pmc
Safety, tolerability, pharmacokinetics, and immunogenicity of an anti-SARS-CoV-2 monoclonal antibody HFB30132A after single dose intravenous administration in healthy Chinese subjects: a phase 1, randomized, double-blind, placebo-controlled study
Safety, tolerability, pharmacokinetics, and immunogenicity of an anti-SARS-CoV-2 monoclonal antibody HFB30132A after single dose intravenous administration in healthy Chinese subjects: a phase 1, randomized, double-blind, placebo-controlled study Abstract Objective: The pandemic of coronavirus disease 2019 (COVID-19) c...
PMC12473409
core_pubmed_pmc
PBPK/PD Model of Vancomycin in Sepsis: Linking Interstitial Exposure in Perfusion-Limited Tissues to MRSA Infection
PBPK/PD Model of Vancomycin in Sepsis: Linking Interstitial Exposure in Perfusion-Limited Tissues to MRSA Infection Abstract Abstract Objective : This study aims to evaluate free vancomycin concentrations in tissues of septic patients that received empirical doses. Methods : A PBPK model was built in PK-Sim to simulate...
PMC9978475
core_pubmed_pmc
Comparison of Yizhiqingxin formula extraction methods and their pharmacodynamic differences
Comparison of Yizhiqingxin formula extraction methods and their pharmacodynamic differences Abstract Objectives This study compared different extraction methods of Yizhiqingxin formula (YQF) and its neuroprotective effects based on pharmacodynamic indices such as learning and memory ability, brain tissue histopathology...
PMC9695976
core_pubmed_pmc
Simultaneous Determination of Moxifloxacin Hydrochloride and Dexamethasone Sodium Phosphate in Rabbit Ocular Tissues and Plasma by LC-MS/MS: Application for Pharmacokinetics Studies
Simultaneous Determination of Moxifloxacin Hydrochloride and Dexamethasone Sodium Phosphate in Rabbit Ocular Tissues and Plasma by LC-MS/MS: Application for Pharmacokinetics Studies Abstract Treatment of ocular infection involves pharmacotherapy with steroids and antibiotic drops, such as moxifloxacin hydrochloride (MF...
PMC8775521
core_pubmed_pmc
Biguanide Pharmaceutical Formulations and the Applications of Bile Acid-Based Nano Delivery in Chronic Medical Conditions
Biguanide Pharmaceutical Formulations and the Applications of Bile Acid-Based Nano Delivery in Chronic Medical Conditions Abstract Biguanides, particularly the widely prescribed drug metformin, have been marketed for many decades and have well-established absorption profiles. They are commonly administered via the oral...
PMC5035790
core_pubmed_pmc
First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas
First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas Abstract This phase I study evaluated the safety, tolerability, and pharmacokinetics of copanlisib, an intravenously administer...
PMC10432884
core_pubmed_pmc
First‐in‐human trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of zagociguat (CY6463), a CNS‐penetrant soluble guanylyl cyclase stimulator
First‐in‐human trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of zagociguat (CY6463), a CNS‐penetrant soluble guanylyl cyclase stimulator Abstract Abstract Soluble guanylate cyclase (sGC) and its product, cyclic guanosine monophosphate, play a role in learning and memory formation. Zagocig...
PMC7188401
core_pubmed_pmc
Preclinical characterization of the ADME properties of a surrogate anti-IL-36R monoclonal antibody antagonist in mouse serum and tissues
Preclinical characterization of the ADME properties of a surrogate anti-IL-36R monoclonal antibody antagonist in mouse serum and tissues Abstract ABSTRACT The decision to pursue a monoclonal antibody (mAb) as a therapeutic for disease intervention requires the assessment of many factors, such as target-biology, includi...
PMC10863906
core_pubmed_pmc
Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling
Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling Abstract Abstract Objective Despite the suggested topiramate serum level of 5–20 mg/L, numerous institutions have observed substantial drug response at lower levels. We aim to investigate the correlation between ...
PMC5107207
core_pubmed_pmc
Development of a Whole-Body Physiologically Based Pharmacokinetic Approach to Assess the Pharmacokinetics of Drugs in Elderly Individuals
Development of a Whole-Body Physiologically Based Pharmacokinetic Approach to Assess the Pharmacokinetics of Drugs in Elderly Individuals Abstract Abstract Background Because of the vulnerability and frailty of elderly adults, clinical drug development has traditionally been biased towards young and middle-aged adults....
PMC5944589
core_pubmed_pmc
Big Data Toolsets to Pharmacometrics: Application of Machine Learning for Time‐to‐Event Analysis
Big Data Toolsets to Pharmacometrics: Application of Machine Learning for Time‐to‐Event Analysis Abstract Abstract Additional value can be potentially created by applying big data tools to address pharmacometric problems. The performances of machine learning (ML) methods and the Cox regression model were evaluated base...
PMC6471907
core_pubmed_pmc
Formulation Development of Albendazole-Loaded Self-Microemulsifying Chewable Tablets to Enhance Dissolution and Bioavailability
Formulation Development of Albendazole-Loaded Self-Microemulsifying Chewable Tablets to Enhance Dissolution and Bioavailability Abstract Abstract Albendazole is an anthelmintic agent with poor solubility and absorption. We developed a chewable tablet (200 mg drug equivalent), containing a self-microemulsifying drug del...
PMC6030392
core_pubmed_pmc
Improved Brain Penetration and Antitumor Efficacy of Temozolomide by Inhibition of ABCB1 and ABCG2 1
Improved Brain Penetration and Antitumor Efficacy of Temozolomide by Inhibition of ABCB1 and ABCG2 1 Abstract The anticancer drug temozolomide is the only drug with proven activity against high-grade gliomas and has therefore become a part of the standard treatment of these tumors. P-glycoprotein (P-gp; ABCB1) and brea...
PMC12645117
core_pubmed_pmc
Limitations and Innovative Application Methods of Surfactants for Solubilization of Poorly Water-Soluble Drugs
Limitations and Innovative Application Methods of Surfactants for Solubilization of Poorly Water-Soluble Drugs Abstract Poor solubility of drugs leads to poor bioavailability and therapeutic efficiency. A large proportion of drugs that are not developed and marketed for use by patients are due to their extremely low so...
PMC4584421
core_pubmed_pmc
Safety, pharmacokinetic and pharmacodynamic properties of TV-1106, a long-acting GH treatment for GH deficiency
Safety, pharmacokinetic and pharmacodynamic properties of TV-1106, a long-acting GH treatment for GH deficiency Abstract Background TV-1106 (Teva Pharmaceuticals) is a genetically fused recombinant protein of human GH (hGH) and human serum albumin, in development for treatment of GH deficiency (GHD). TV-1106 is expecte...
PMC8398354
core_pubmed_pmc
The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity
The Psychonauts’ Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity Abstract Designer benzodiazepines (DBZDs) represent a serious health concern and are increasingly reported in polydrug consumption-related fatalities. When new DBZDs are ide...
PMC12884390
core_pubmed_pmc
Mechanistic and therapeutic dimensions of DcR3-mediated immunomodulation in sepsis
Mechanistic and therapeutic dimensions of DcR3-mediated immunomodulation in sepsis Abstract Sepsis is a life-threatening syndrome characterized by dysregulated host-immune responses, progressing through hyperinflammatory and immunosuppressive stages. Decoy receptor 3 (DcR3), a soluble member of the TNF receptor superfa...
PMC8272888
core_pubmed_pmc
Repurposing FDA-approved drugs against multiple proteins of SARS-CoV-2: An in silico study
Repurposing FDA-approved drugs against multiple proteins of SARS-CoV-2: An in silico study Abstract Abstract The current crisis of the COVID-19 pandemic around the world has been devastating as many lives have been lost to the novel SARS CoV-2 virus. Thus, there is an urgent need for the right therapeutic drug to curb ...
PMC5626687
core_pubmed_pmc
Evaluation of the heterogeneous tissue distribution of erlotinib in lung cancer using matrix-assisted laser desorption ionization mass spectrometry imaging
Evaluation of the heterogeneous tissue distribution of erlotinib in lung cancer using matrix-assisted laser desorption ionization mass spectrometry imaging Abstract Although drug distribution in tumor tissues has a significant impact on efficacy, conventional pharmacokinetic analysis has some limitations with regard to...
PMC11337614
core_pubmed_pmc
Targeting gut-microbiota for gastric cancer treatment: a systematic review
Targeting gut-microbiota for gastric cancer treatment: a systematic review Abstract Background Preclinical research has identified the mechanisms via which bacteria influence cancer treatment outcomes. Clinical studies have demonstrated the potential to modify the microbiome in cancer treatment. Herein, we systematical...
PMC5125732
core_pubmed_pmc
PBPK modeling and simulation in drug research and development
PBPK modeling and simulation in drug research and development Abstract Abstract Physiologically based pharmacokinetic (PBPK) modeling and simulation can be used to predict the pharmacokinetic behavior of drugs in humans using preclinical data. It can also explore the effects of various physiologic parameters such as ag...
PMC12767388
core_pubmed_pmc
Targeting NRF2 With Isoeugenol: A Promising Small Molecule for Neurodegenerative, Metabolic, and Chronic Inflammatory Disorders
Targeting NRF2 With Isoeugenol: A Promising Small Molecule for Neurodegenerative, Metabolic, and Chronic Inflammatory Disorders Abstract Oxidative stress, driven by an imbalance between oxidants and antioxidants, disrupts redox homeostasis and contributes to the development of chronic diseases, including cancer, diabet...
PMC6853277
core_pubmed_pmc
Using mechanistic physiologically-based pharmacokinetic models to assess prenatal drug exposure: Thalidomide versus efavirenz as case studies
Using mechanistic physiologically-based pharmacokinetic models to assess prenatal drug exposure: Thalidomide versus efavirenz as case studies Abstract Abstract Maternofoetal physiologically-based pharmacokinetic models integrating multi-compartmental maternal and foetal units were developed using Simbiology® to estimat...
PMC8940759
core_pubmed_pmc
A series acceleration algorithm for the gamma-Pareto (type I) convolution and related functions of interest for pharmacokinetics
A series acceleration algorithm for the gamma-Pareto (type I) convolution and related functions of interest for pharmacokinetics Abstract Abstract The gamma-Pareto type I convolution (GPC type I) distribution, which has a power function tail, was recently shown to describe the disposition kinetics of metformin in dogs ...
PMC9868173
core_pubmed_pmc
Pharmacological activities and mechanisms of action of hypophyllanthin: A review
Pharmacological activities and mechanisms of action of hypophyllanthin: A review Abstract Abstract Hypophyllanthin is a major lignan present in various Phyllanthus species and has been used as one of the bioactive chemical markers for quality control purposes as it contributes to their diverse pharmacological activitie...
PMC12910213
core_pubmed_pmc
A prospective feasibility study evaluating the implementation of model-informed precision dosing in critically ill children
A prospective feasibility study evaluating the implementation of model-informed precision dosing in critically ill children Abstract Achieving optimal antibiotic exposure in critically ill pediatric patients is difficult due to (their) dynamic physiology and variability. Conventional weight-based regimens often fail to...
PMC9345828
core_pubmed_pmc
The Options for Neuraxial Drug Administration
The Options for Neuraxial Drug Administration Abstract Neuraxial drug administration, i.e., the injection of drugs into the epidural or intrathecal space to produce anesthesia or analgesia, is a technique developed more than 120 years ago. Today, it still is widely used in daily practice in anesthesiology and in acute ...
PMC11742280
core_pubmed_pmc
A phase I study of MLN4924 and belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome
A phase I study of MLN4924 and belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome Abstract Purpose Relapsed and/or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome continue to have a poor prognosis with limited treatment options despite advancements in rational ...
PMC10652308
core_pubmed_pmc
Efficacy and safety of abemaciclib alone and with PI3K/mTOR inhibitor LY3023414 or galunisertib versus chemotherapy in previously treated metastatic pancreatic adenocarcinoma: A randomized controlled trial
Efficacy and safety of abemaciclib alone and with PI3K/mTOR inhibitor LY3023414 or galunisertib versus chemotherapy in previously treated metastatic pancreatic adenocarcinoma: A randomized controlled trial Abstract Abstract Background Pancreatic ductal adenocarcinomas (PDAC) are characterized by frequent cell cycle pat...
PMC9964875
core_pubmed_pmc
A Rapid and Sensitive UHPLC–MS/MS Method for Determination of Chlorogenic Acid and Its Application to Distribution and Neuroprotection in Rat Brain
A Rapid and Sensitive UHPLC–MS/MS Method for Determination of Chlorogenic Acid and Its Application to Distribution and Neuroprotection in Rat Brain Abstract Chlorogenic acid (5-CQA) is a phenolic natural product that has been reported to improve neurobehavioral disorders and brain injury. However, its pharmacokinetics ...
PMC11521577
core_pubmed_pmc
Supratherapeutic International Normalized Ratio in a Patient on Warfarin Following Initiation of Brexpiprazole Pharmacotherapy: A Case Report
Supratherapeutic International Normalized Ratio in a Patient on Warfarin Following Initiation of Brexpiprazole Pharmacotherapy: A Case Report Abstract Abstract Many medications have established interactions with warfarin, potentially affecting international normalized ratio (INR) levels and increasing the risk of bleed...
PMC12592267
core_pubmed_pmc
Changes in the Fraction Metabolized in Children Younger than Four Years; When is Clearance Scaling for the Dominant Elimination Route in Adults Appropriate?
Changes in the Fraction Metabolized in Children Younger than Four Years; When is Clearance Scaling for the Dominant Elimination Route in Adults Appropriate? Abstract Introduction A common approach to scaling clearance from adults to children is to apply a maturation function for the dominant elimination pathway in adul...
PMC11581887
core_pubmed_pmc
Combined carbapenem resulted in a 4.48-fold increase in valproic acid clearance: a population pharmacokinetic model in Chinese children and adults with epilepsy or after neurosurgery
Combined carbapenem resulted in a 4.48-fold increase in valproic acid clearance: a population pharmacokinetic model in Chinese children and adults with epilepsy or after neurosurgery Abstract Abstract Our study aims to explore the pharmacokinetics of valproic acid (VPA) in Chinese patients with epilepsy or after neuros...
PMC7819529
core_pubmed_pmc
Rifampicin Can Be Given as Flat-Dosing Instead of Weight-Band Dosing
Rifampicin Can Be Given as Flat-Dosing Instead of Weight-Band Dosing Abstract Abstract Background The weight-band dosing in tuberculosis treatment regimen has been implemented in clinical practice for decades. Patients will receive different number of fixed dose combination tablets according to their weight-band. Howev...
PMC12271520
core_pubmed_pmc
Ceftazidime–Avibactam Pharmacokinetic Comparative In Vivo/In Vitro Study in a Critically Ill Children Under High‐Volume Continuous Venovenous Hemodiafiltration
Ceftazidime–Avibactam Pharmacokinetic Comparative In Vivo/In Vitro Study in a Critically Ill Children Under High‐Volume Continuous Venovenous Hemodiafiltration Abstract ABSTRACT Ceftazidime–avibactam is a novel cephalosporin/beta‐lactamase inhibitor combination developed to address increasing antimicrobial resistance. ...
PMC6534253
core_pubmed_pmc
Stereoselective pharmacokinetic and pharmacodynamic analysis of a CNS-active sulphamoylphenyl carbamate derivative
Stereoselective pharmacokinetic and pharmacodynamic analysis of a CNS-active sulphamoylphenyl carbamate derivative Abstract Abstract 3-Methylpentyl(4-sulphamoylphenyl)carbamate (MSPC) came as the most potent compound out of a new series of carbamates composed of phenyl-ethanol or branched aliphatic alcohols, and 4-benz...
PMC11250107
core_pubmed_pmc
Pharmacokinetics of Generic Pediatric Dolutegravir Dispersible Tablet in Thai Young Children Living With HIV Weighing Below Twenty Kilograms
Pharmacokinetics of Generic Pediatric Dolutegravir Dispersible Tablet in Thai Young Children Living With HIV Weighing Below Twenty Kilograms Abstract Abstract Introduction: Dolutegravir (DTG) dispersible tablet (DTG-DT) is a pediatric-friendly formulation. We aimed to describe the pharmacokinetics and virologic respons...
PMC4932535
core_pubmed_pmc
Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis
Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis Abstract Abstract Aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of therapy for the treatment of idiopathic pericarditis (IP). A comprehensive review consisting of ...
PMC12037436
core_pubmed_pmc
Stable self-assembled oral metformin-bridged nanocochleates against hepatocellular carcinoma
Stable self-assembled oral metformin-bridged nanocochleates against hepatocellular carcinoma Abstract Abstract Despite its established anti-diabetic activity, Metformin hydrochloride (MET) has been repurposed for the management of hepatocellular carcinoma (HCC). Owing to MET high aqueous solubility and poor oral permea...
PMC9478891
core_pubmed_pmc
PBPK-PD modeling for the preclinical development and clinical translation of tau antibodies for Alzheimer’s disease
PBPK-PD modeling for the preclinical development and clinical translation of tau antibodies for Alzheimer’s disease Abstract Disrupted tau proteostasis and transneuronal spread is a pathological hallmark of Alzheimer’s disease. Neurodegenerative diseases remain an unmet medical need and novel disease modifying therapeu...
PMC7982536
core_pubmed_pmc
Individualizing Therapy in CIDP: A Mini-Review Comparing the Pharmacokinetics of Ig With SCIg and IVIg
Individualizing Therapy in CIDP: A Mini-Review Comparing the Pharmacokinetics of Ig With SCIg and IVIg Abstract Immunoglobulin (Ig) therapy is a first-line treatment for CIDP, which can be administered intravenously (IVIg) or subcutaneously (SCIg) and is often required long term. The differences between these modes of ...
PMC7070803
core_pubmed_pmc
Pharmacokinetics and Pharmacodynamics of Intramuscular and Oral Betamethasone and Dexamethasone in Reproductive Age Women in India
Pharmacokinetics and Pharmacodynamics of Intramuscular and Oral Betamethasone and Dexamethasone in Reproductive Age Women in India Abstract High‐dose betamethasone and dexamethasone are standard of care treatments for women at risk of preterm delivery to improve neonatal respiratory and mortality outcomes. The dose in ...
PMC7513528
core_pubmed_pmc
Lung function, pharmacokinetics, and tolerability of inhaled indacaterol maleate and acetate in asthma patients
Lung function, pharmacokinetics, and tolerability of inhaled indacaterol maleate and acetate in asthma patients Abstract Background Indacaterol maleate delivered with the Breezhaler® inhalation device is a long-acting β 2 -agonist approved for chronic obstructive pulmonary disease. In the development of a once daily, i...
PMC9329868
core_pubmed_pmc
Is Silver the New Gold? A Systematic Review of the Preclinical Evidence of Its Use in Bone Substitutes as Antiseptic
Is Silver the New Gold? A Systematic Review of the Preclinical Evidence of Its Use in Bone Substitutes as Antiseptic Abstract Antibiotic-laden bone substitutes represent a viable option in the treatment of bone and joint infections with bone defects. In particular, the addition of silver ions or silver nanoparticles to...
PMC9311525
core_pubmed_pmc
Towards Improved Management of Tuberculous Bloodstream Infections: Pharmacokinetic Considerations with Suggestions for Better Treatment Outcomes
Towards Improved Management of Tuberculous Bloodstream Infections: Pharmacokinetic Considerations with Suggestions for Better Treatment Outcomes Abstract Mycobacterium tuberculosis is the leading cause of sepsis among HIV-infected adults, yet effective treatment remains a challenge. Efficacy of antituberculous drugs is...
PMC12587311
core_pubmed_pmc
Early Higher Plasma Regorafenib Concentration Predicts Shorter PFS in Japanese Patients With mCRC
Early Higher Plasma Regorafenib Concentration Predicts Shorter PFS in Japanese Patients With mCRC Abstract ABSTRACT The pharmacokinetics of regorafenib and its active metabolites, M2 and M5, vary widely among individual patients. However, the relationship between these plasma concentrations and therapeutic efficacy rem...
PMC12334468
core_pubmed_pmc
Application of Physiologically-Based Pharmacokinetic (PBPK) Model in Drug Development and in Dietary Phytochemicals
Application of Physiologically-Based Pharmacokinetic (PBPK) Model in Drug Development and in Dietary Phytochemicals Abstract Abstract Purpose of review Physiologically-based pharmacokinetic (PBPK) modeling is a powerful tool to understand drug movements throughout the human body. Unlike classical PK methods that often ...
PMC8252714
core_pubmed_pmc
Ibuprofen enantiomers in premature neonates with patent ductus arteriosus: Preliminary data on an unexpected pharmacokinetic profile of S (+)‐ibuprofen
Ibuprofen enantiomers in premature neonates with patent ductus arteriosus: Preliminary data on an unexpected pharmacokinetic profile of S (+)‐ibuprofen Abstract Abstract S (+)‐ibuprofen ( S ‐IBU) and R (−)‐ibuprofen ( R ‐IBU) concentrations were measured in 16 neonates with patent ductus arteriosus during a cycle of th...
PMC10772478
core_pubmed_pmc
Pharmacokinetics and pharmacodynamics of cannabis‐based medicine in a patient population included in a randomized, placebo‐controlled, clinical trial
Pharmacokinetics and pharmacodynamics of cannabis‐based medicine in a patient population included in a randomized, placebo‐controlled, clinical trial Abstract Abstract Information on the pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered cannabis‐based medicine (CBM) in capsule formulation in patien...
PMC5418449
core_pubmed_pmc
Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy
Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy Abstract Abstract Background: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterise...
PMC8425638
core_pubmed_pmc
In vivo trafficking of a tumor-targeting IgE antibody: molecular imaging demonstrates rapid hepatobiliary clearance compared to IgG counterpart
In vivo trafficking of a tumor-targeting IgE antibody: molecular imaging demonstrates rapid hepatobiliary clearance compared to IgG counterpart Abstract ABSTRACT IgE antibodies elicit powerful immune responses, recruiting effector cells to tumors more efficiently and with greater cytotoxicity than IgG antibodies. Conse...
PMC12712391
core_pubmed_pmc
The Second Mitochondria‐Derived Activator of Caspases Mimetic BI 891065 in Patients With Advanced Solid Tumors: Results From Two Phase I Studies
The Second Mitochondria‐Derived Activator of Caspases Mimetic BI 891065 in Patients With Advanced Solid Tumors: Results From Two Phase I Studies Abstract ABSTRACT Introduction BI 891065, a second mitochondria‐derived activator of caspases mimetic targets the inhibitor of apoptosis (IAP) family member cIAP1. We describe...
PMC8465969
core_pubmed_pmc
The Effect of Cannabis-Based Medicine on Neuropathic Pain and Spasticity in Patients with Multiple Sclerosis and Spinal Cord Injury: Study Protocol of a National Multicenter Double-Blinded, Placebo-Controlled Trial
The Effect of Cannabis-Based Medicine on Neuropathic Pain and Spasticity in Patients with Multiple Sclerosis and Spinal Cord Injury: Study Protocol of a National Multicenter Double-Blinded, Placebo-Controlled Trial Abstract Disease or acquired damage to the central nervous system frequently causes disabling spasticity ...
PMC12757702
core_pubmed_pmc
Enhanced Vatiquinone Bioavailability With Fatty Meals and Optimal Dosing Schedule
Enhanced Vatiquinone Bioavailability With Fatty Meals and Optimal Dosing Schedule Abstract ABSTRACT Vatiquinone, a 15‐lipoxygenase (LO) inhibitor, is an orally bioavailable small molecule being developed for the treatment of Friedreich's ataxia, a disorder characterized by high levels of oxidative stress and dysregulat...
PMC12314501
core_pubmed_pmc
Thigh Injections of Cabotegravir + Rilpivirine in Virally Suppressed Adults With HIV-1: A Substudy of the Phase 3b ATLAS-2M Study
Thigh Injections of Cabotegravir + Rilpivirine in Virally Suppressed Adults With HIV-1: A Substudy of the Phase 3b ATLAS-2M Study Abstract Abstract Background Cabotegravir + rilpivirine (CAB + RPV) administered via intramuscular gluteal injections is the first complete long-acting regimen for maintaining human immunode...
PMC10343629
core_pubmed_pmc
In Silico Studies of Novel Vemurafenib Derivatives as BRAF Kinase Inhibitors
In Silico Studies of Novel Vemurafenib Derivatives as BRAF Kinase Inhibitors Abstract BRAF inhibitors have improved the treatment of advanced or metastatic melanoma in patients that harbor a BRAF T1799A mutation. Because of new insights into the role of aberrant glycosylation in drug resistance, we designed and studied...
PMC12789425
core_pubmed_pmc
Discovery of thiadiazole-based small-molecule inhibitors of SARS-CoV-2 spike-ACE2 interaction through integrated computational prediction and experimental validation
Discovery of thiadiazole-based small-molecule inhibitors of SARS-CoV-2 spike-ACE2 interaction through integrated computational prediction and experimental validation Abstract Abstract The SARS-CoV-2 spike protein enables viral entry by binding to the human ACE2 receptor, making it a critical target for antiviral interv...
PMC5644636
core_pubmed_pmc
Mechanisms of Drug Resistance in Veterinary Oncology—A Review with an Emphasis on Canine Lymphoma
Mechanisms of Drug Resistance in Veterinary Oncology—A Review with an Emphasis on Canine Lymphoma Abstract Abstract Drug resistance (DR) is the major limiting factor in the successful treatment of systemic neoplasia with cytotoxic chemotherapy. DR can be either intrinsic or acquired, and although the development and cl...
PMC7139065
core_pubmed_pmc
An approach to antibiotic treatment in patients with sepsis
An approach to antibiotic treatment in patients with sepsis Abstract Abstract Sepsis is a medical emergency and life-threatening condition due to a dysregulated host response to infection, which is time-dependent and associated with unacceptably high mortality. Thus, when treating suspicious or confirmed cases of sepsi...
PMC8282371
core_pubmed_pmc
Pharmacokinetics and Tissue Distribution of Combined Triptolide and Paeoniflorin Regimen for Percutaneous Administration in Rats Assessed by Liquid Chromatography-Tandem Mass Spectrometry
Pharmacokinetics and Tissue Distribution of Combined Triptolide and Paeoniflorin Regimen for Percutaneous Administration in Rats Assessed by Liquid Chromatography-Tandem Mass Spectrometry Abstract Abstract Triptolide (TP) has shown potential in rheumatoid arthritis (RA) treatment, but the narrow therapeutic window limi...
PMC9652429
core_pubmed_pmc
Human radiolabeled mass balance studies supporting the FDA approval of new drugs
Human radiolabeled mass balance studies supporting the FDA approval of new drugs Abstract Abstract Human radiolabeled mass balance studies are an important component of the clinical pharmacology programs supporting the development of new investigational drugs. These studies allow for understanding of the absorption, di...
PMC4685605
core_pubmed_pmc
Historical Context and Recent Advances in Exposure-Response Estimation for Deriving Occupational Exposure Limits
Historical Context and Recent Advances in Exposure-Response Estimation for Deriving Occupational Exposure Limits Abstract Abstract Virtually no occupational exposure standards specify the level of risk for the prescribed exposure, and most occupational exposure limits are not based on quantitative risk assessment (QRA)...
PMC10026531
core_pubmed_pmc
Population Pharmacokinetic Modeling and Exposure‐Response Analysis for Aripiprazole Once Monthly in Subjects With Schizophrenia
Population Pharmacokinetic Modeling and Exposure‐Response Analysis for Aripiprazole Once Monthly in Subjects With Schizophrenia Abstract Abstract An intramuscular formulation of aripiprazole monohydrate dosed once monthly (AOM) was developed to address nonadherence with the approved oral tablets. A 3‐compartment linear...
PMC11652822
core_pubmed_pmc
Harnessing Pharmacogenomics in Clinical Research on Psychedelic‐Assisted Therapy
Harnessing Pharmacogenomics in Clinical Research on Psychedelic‐Assisted Therapy Abstract Abstract Psychedelics have recently re‐emerged as potential treatments for various psychiatric conditions that impose major public health costs and for which current treatment options have limited efficacy. At the same time, perso...
PMC10805834
core_pubmed_pmc
Population pharmacokinetic modeling of ilaprazole in healthy subjects and patients with duodenal ulcer in China
Population pharmacokinetic modeling of ilaprazole in healthy subjects and patients with duodenal ulcer in China Abstract Abstract Aims: This study aimed to develop a population pharmacokinetic (PopPK) model of ilaprazole in healthy subjects and patients with duodenal ulcer in Chinese and investigate the effect of poten...
PMC6616216
core_pubmed_pmc
Clinical Pharmacokinetics of a Lipid-Based Formulation of Risperidone, VAL401: Analysis of a Single Dose in an Open-Label Trial of Late-Stage Cancer Patients
Clinical Pharmacokinetics of a Lipid-Based Formulation of Risperidone, VAL401: Analysis of a Single Dose in an Open-Label Trial of Late-Stage Cancer Patients Abstract Abstract Background and Objectives A clinical trial was conducted to measure and analyse the pharmacokinetic parameters of a lipid formulation of risperi...
PMC11818058
core_pubmed_pmc
Combinatorial Effects of Cisplatin and PARP Inhibitor Olaparib on Survival, Intestinal Integrity, and Microbiome Modulation in Murine Model
Combinatorial Effects of Cisplatin and PARP Inhibitor Olaparib on Survival, Intestinal Integrity, and Microbiome Modulation in Murine Model Abstract This study investigated the effects of the poly (ADP-ribose) polymerase (PARP) inhibitor Olaparib, alone and in combination with cisplatin, on intestinal integrity, surviv...
PMC12389047
core_pubmed_pmc
Population Pharmacokinetic Modeling of Piperacillin/Tazobactam in Healthy Adults and Exploration of Optimal Dosing Strategies
Population Pharmacokinetic Modeling of Piperacillin/Tazobactam in Healthy Adults and Exploration of Optimal Dosing Strategies Abstract Abstract Background/Objectives: Current dosing recommendations for piperacillin/tazobactam suggest adjustments only for patients with creatinine clearance (CrCl) below 40 mL/min, potent...
PMC11658602
core_pubmed_pmc
In vivo imaging and pharmacokinetics of percutaneously injected ultrasound and X-ray imageable thermosensitive hydrogel loaded with doxorubicin versus free drug in swine
In vivo imaging and pharmacokinetics of percutaneously injected ultrasound and X-ray imageable thermosensitive hydrogel loaded with doxorubicin versus free drug in swine Abstract Intratumoral injections often lack visibility, leading to unpredictable outcomes such as incomplete tumor coverage, off-target drug delivery ...
PMC10869334
core_pubmed_pmc
In vitro pharmacokinetics/pharmacodynamics of the β-lactamase inhibitor, durlobactam, in combination with sulbactam against Acinetobacter baumannii-calcoaceticus complex
In vitro pharmacokinetics/pharmacodynamics of the β-lactamase inhibitor, durlobactam, in combination with sulbactam against Acinetobacter baumannii-calcoaceticus complex Abstract ABSTRACT Infections caused by Acinetobacter baumannii are increasingly multidrug resistant and associated with high rates of morbidity and mo...
PMC7970330
core_pubmed_pmc
Towards a mechanistic understanding of reciprocal drug–microbiome interactions
Towards a mechanistic understanding of reciprocal drug–microbiome interactions Abstract Abstract Broad‐spectrum antibiotics target multiple gram‐positive and gram‐negative bacteria, and can collaterally damage the gut microbiota. Yet, our knowledge of the extent of damage, the antibiotic activity spectra, and the resis...
PMC12587533
core_pubmed_pmc
A first-in-human phase I study to evaluate the safety, tolerability, and pharmacokinetics of a novel anti-influenza agent suraxavir marboxil in healthy Chinese subjects
A first-in-human phase I study to evaluate the safety, tolerability, and pharmacokinetics of a novel anti-influenza agent suraxavir marboxil in healthy Chinese subjects Abstract ABSTRACT Suraxavir marboxil (GP681) is a prodrug of a novel polymerase acidic protein inhibitor, and its metabolite GP1707D07 prevents the rep...