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PMC8283551
core_pubmed_pmc
Study protocol for a phase 2A trial of the safety and tolerability of increased dose rifampicin and adjunctive linezolid, with or without aspirin, for HIV-associated tuberculous meningitis [LASER-TBM]
Study protocol for a phase 2A trial of the safety and tolerability of increased dose rifampicin and adjunctive linezolid, with or without aspirin, for HIV-associated tuberculous meningitis [LASER-TBM] Abstract Background: Tuberculous meningitis (TBM) is the most lethal form of tuberculosis with a mortality of ~50% in t...
PMC9598284
core_pubmed_pmc
A Minimal Physiologically Based Pharmacokinetic Model to Characterize CNS Distribution of Metronidazole in Neuro Care ICU Patients
A Minimal Physiologically Based Pharmacokinetic Model to Characterize CNS Distribution of Metronidazole in Neuro Care ICU Patients Abstract Abstract Understanding antibiotic concentration-time profiles in the central nervous system (CNS) is crucial to treat severe life-threatening CNS infections, such as nosocomial ven...
PMC6333349
core_pubmed_pmc
The influence of concomitant antiepileptic drugs on lamotrigine serum concentrations in Northwest Chinese Han population with epilepsy
The influence of concomitant antiepileptic drugs on lamotrigine serum concentrations in Northwest Chinese Han population with epilepsy Abstract Objective The aims of this study were to identify the influencing factors such as gender, age, dose and combinations of other antiepileptic drugs (AEDs), especially in triple c...
PMC11361584
core_pubmed_pmc
Development and validation of a reversed-phase HPLC-UV method for simultaneous determination of levosulpiride and omeprazole in human plasma: Applicability of the method for evaluation of pharmacokinetic drug-drug interactions
Development and validation of a reversed-phase HPLC-UV method for simultaneous determination of levosulpiride and omeprazole in human plasma: Applicability of the method for evaluation of pharmacokinetic drug-drug interactions Abstract Levosulpiride and omeprazole are co-prescribed for gastrointestinal disorders associ...
PMC3590411
core_pubmed_pmc
Ten Years of Experience with Biphasic Insulin Aspart 30
Ten Years of Experience with Biphasic Insulin Aspart 30 Abstract Biphasic insulin aspart 30 (BIAsp 30) includes 30% soluble rapid-acting insulin aspart (IAsp) along with an intermediate-acting 70% protaminated IAsp that provides coverage of prandial and basal insulin in a single injection. As BIAsp 30 has been availabl...
PMC6272185
core_pubmed_pmc
Antimycobacterial and Anti-Inflammatory Activities of Substituted Chalcones Focusing on an Anti-Tuberculosis Dual Treatment Approach
Antimycobacterial and Anti-Inflammatory Activities of Substituted Chalcones Focusing on an Anti-Tuberculosis Dual Treatment Approach Abstract Abstract Tuberculosis (TB) remains a serious public health problem aggravated by the emergence of M. tuberculosis (Mtb) strains resistant to multiple drugs (MDR). Delay in TB tre...
PMC9607246
core_pubmed_pmc
Population Pharmacokinetic/Pharmacodynamic Modelling of Daptomycin for Schedule Optimization in Patients with Renal Impairment
Population Pharmacokinetic/Pharmacodynamic Modelling of Daptomycin for Schedule Optimization in Patients with Renal Impairment Abstract Abstract The aims of this study are (i) to develop a population pharmacokinetic/pharmacodynamic model of daptomycin in patients with normal and impaired renal function, and (ii) to est...
PMC4363212
core_pubmed_pmc
Tedizolid Phosphate: a Next-Generation Oxazolidinone
Tedizolid Phosphate: a Next-Generation Oxazolidinone Abstract Treatment of multidrug-resistant Gram-positive infections continues to challenge clinicians as the emergence of new resistance mechanisms outpaces introduction of novel antimicrobial agents. Tedizolid phosphate is a next-generation oxazolidinone with activit...
PMC8409942
core_pubmed_pmc
Immunosuppressive effect of PLGA-FK506-NPs in treatment of acute cardiac rejection via topical subcutaneous injection
Immunosuppressive effect of PLGA-FK506-NPs in treatment of acute cardiac rejection via topical subcutaneous injection Abstract Abstract FK506, a first-line immunosuppressant, is routinely administered orally and intravenously to inhibit activation and proliferation of T cells after heart transplantation (HT). Current a...
PMC7508576
core_pubmed_pmc
Relationship between Gepotidacin Exposure and Prevention of On-Therapy Resistance Amplification in a Neisseria gonorrhoeae Hollow-Fiber In Vitro Infection Model
Relationship between Gepotidacin Exposure and Prevention of On-Therapy Resistance Amplification in a Neisseria gonorrhoeae Hollow-Fiber In Vitro Infection Model Abstract Multidrug-resistant Neisseria gonorrhoeae has emerged as a threat to global health. The relationship between gepotidacin exposure and prevention of on...
PMC7388563
core_pubmed_pmc
Population pharmacokinetics model and initial dose optimization of tacrolimus in children and adolescents with lupus nephritis based on real-world data
Population pharmacokinetics model and initial dose optimization of tacrolimus in children and adolescents with lupus nephritis based on real-world data Abstract Abstract The present study aimed to establish a population pharmacokinetics model of tacrolimus and further optimize the initial dosing regimen of tacrolimus i...
PMC12712551
core_pubmed_pmc
An Open Label, Randomized, Comparative Bioavailability Study of BioTurm™ Extract Versus Curcuma longa Extract With Piperine in Healthy Adult Volunteers
An Open Label, Randomized, Comparative Bioavailability Study of BioTurm™ Extract Versus Curcuma longa Extract With Piperine in Healthy Adult Volunteers Abstract Abstract Introduction Curcumin (95%) from Curcuma longa rhizomes holds significant therapeutic promise, but its clinical efficacy is limited by poor oral bioav...
PMC10196421
core_pubmed_pmc
Relationship between factor VIII levels and bleeding for rFVIII‐SingleChain in severe hemophilia A: A repeated time‐to‐event analysis
Relationship between factor VIII levels and bleeding for rFVIII‐SingleChain in severe hemophilia A: A repeated time‐to‐event analysis Abstract Abstract Publications on the exposure‐effect relationships of factor concentrates for hemophilia treatment are limited, whereas such analyses give insight on treatment efficacy....
PMC9960599
core_pubmed_pmc
Considerations for Intravenous Anesthesia Dose in Obese Children: Understanding PKPD
Considerations for Intravenous Anesthesia Dose in Obese Children: Understanding PKPD Abstract The intravenous induction or loading dose in children is commonly prescribed per kilogram. That dose recognizes the linear relationship between volume of distribution and total body weight. Total body weight comprises both fat...
PMC6256002
core_pubmed_pmc
Influence of age and renal impairment on the steady state pharmacokinetics of filgotinib, a selective JAK1 inhibitor
Influence of age and renal impairment on the steady state pharmacokinetics of filgotinib, a selective JAK1 inhibitor Abstract Abstract Aims Filgotinib (GS‐6034, formerly GLPG0634) is an oral, selective Janus kinase 1 (JAK1) inhibitor that showed early response and sustained efficacy in patients with rheumatoid arthriti...
PMC8891439
core_pubmed_pmc
Impact of Irradiation on the Pharmacokinetics and Biotransformation of Tamoxifen
Impact of Irradiation on the Pharmacokinetics and Biotransformation of Tamoxifen Abstract Abstract Background The optimal procedure for combining radiotherapy (RT) with tamoxifen treatment is controversial as RT may alter the pharmacokinetics and biotransformation of tamoxifen. The present study investigated this poten...
PMC9395984
core_pubmed_pmc
Drug-drug interactions between antithrombotics and direct-acting antivirals in hepatitis C virus (HCV) patients: A brief, updated report
Drug-drug interactions between antithrombotics and direct-acting antivirals in hepatitis C virus (HCV) patients: A brief, updated report Abstract Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease affecting over 71 million people worldwide. An increased incidence of atherothrombotic events [e...
PMC3160947
core_pubmed_pmc
Microemulsion-based novel transdermal delivery system of tetramethylpyrazine: preparation and evaluation in vitro and in vivo
Microemulsion-based novel transdermal delivery system of tetramethylpyrazine: preparation and evaluation in vitro and in vivo Abstract Objective To deliver 2,3,5,6-tetramethylpyrazine (TMP) in a relatively large dose through a transdermal route and facilitate the practical application of microemulison in transdermal dr...
PMC7321154
core_pubmed_pmc
Pharmacokinetic Properties of 68 Ga-labelled Folic Acid Conjugates: Improvement Using HEHE Tag
Pharmacokinetic Properties of 68 Ga-labelled Folic Acid Conjugates: Improvement Using HEHE Tag Abstract Abstract The folate receptor (FR) is a promising cell membrane-associated target for molecular imaging and radionuclide therapy of cancer (FR-α) and potentially also inflammatory diseases (FR-β) through use of folic ...
PMC12024006
core_pubmed_pmc
Pharmacokinetics, Withdrawal Time, and Physiological Effects of Single Oral Administration of Enrofloxacin in Dybowski’s Frog ( Rana dybowskii )
Pharmacokinetics, Withdrawal Time, and Physiological Effects of Single Oral Administration of Enrofloxacin in Dybowski’s Frog ( Rana dybowskii ) Abstract Background : As a broad-spectrum fluoroquinolone, enrofloxacin (ENR) is commonly employed to manage bacterial infections in aquatic species. Nevertheless, there have ...
PMC6798029
core_pubmed_pmc
Pharmacokinetics and Pharmacodynamics of Gamithromycin Treatment of Pasteurella multocida in a Murine Lung Infection Model
Pharmacokinetics and Pharmacodynamics of Gamithromycin Treatment of Pasteurella multocida in a Murine Lung Infection Model Abstract Abstract Gamithromycin is approved for the treatment and prevention of bovine respiratory disease (BRD), which is caused mainly by Mannheimia haemolytica, Pasteurella multocida, Histophilu...
PMC5986681
core_pubmed_pmc
Population Pharmacokinetic Analysis of Asunaprevir in Subjects with Hepatitis C Virus Infection
Population Pharmacokinetic Analysis of Asunaprevir in Subjects with Hepatitis C Virus Infection Abstract Abstract Introduction Asunaprevir (ASV) is a potent, pangenotypic, twice-daily hepatitis C virus (HCV) NS3 inhibitor indicated for the treatment of chronic HCV infection. Methods A population pharmacokinetic (PPK) m...
PMC11743626
core_pubmed_pmc
Evaluation of the effectiveness of GASMAN anesthesia simulation software combined with case-based learning versus traditional lecture-based learning in inhalation anesthesia education
Evaluation of the effectiveness of GASMAN anesthesia simulation software combined with case-based learning versus traditional lecture-based learning in inhalation anesthesia education Abstract Abstract Objective To evaluate the effectiveness of integrating GASMAN anesthesia simulation software with case-based learning ...
PMC12447529
core_pubmed_pmc
Ibrexafungerp: Mechanism of Action, Clinical, and Translational Science
Ibrexafungerp: Mechanism of Action, Clinical, and Translational Science Abstract ABSTRACT Ibrexafungerp is a first‐in‐class triterpenoid antifungal that targets β‐(1,3)‐glucan synthase in fungal cell wall development. It is indicated for vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) in ad...
PMC6508715
core_pubmed_pmc
Neoadjuvant therapy for locally advanced gastric cancer patients. A population pharmacodynamic modeling
Neoadjuvant therapy for locally advanced gastric cancer patients. A population pharmacodynamic modeling Abstract Abstract Background Perioperative chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC) has been shown to improve ...
PMC12538932
core_pubmed_pmc
Renal maturation and catch-up clearance of ganciclovir in a preterm neonate: Bayesian pharmacokinetic analysis using a population model
Renal maturation and catch-up clearance of ganciclovir in a preterm neonate: Bayesian pharmacokinetic analysis using a population model Abstract Background Congenital cytomegalovirus (CMV) infection is a major cause of neonatal morbidity. However, optimizing ganciclovir (GCV) dosing in preterm infants is complicated by...
PMC5515048
core_pubmed_pmc
Pharmacokinetics-based adherence measures for antiretroviral therapy in HIV-infected Kenyan children
Pharmacokinetics-based adherence measures for antiretroviral therapy in HIV-infected Kenyan children Abstract Abstract Background : Traditional medication adherence measures do not account for the pharmacokinetic (PK) properties of the drugs, potentially misrepresenting true therapeutic exposure. Methods : In a populat...
PMC11990103
core_pubmed_pmc
Anticancer Activity and Safety Profile of Novel 1-(4-Fluorophenoxyacetyl)-4-substituted Thio/Semicarbazide Derivatives
Anticancer Activity and Safety Profile of Novel 1-(4-Fluorophenoxyacetyl)-4-substituted Thio/Semicarbazide Derivatives Abstract Compounds with thiosemicarbazide and semicarbazide scaffolds are among the most promising structures in medicinal chemistry due to the possibility of forming multiple hydrogen bonds. Therefore...
PMC12017596
core_pubmed_pmc
Prasugrel Intermediate Metabolite Modulates Platelet Inhibition by Negatively Interfering With an Active Metabolite: An Ex Vivo, In Vitro, and In Silico Study
Prasugrel Intermediate Metabolite Modulates Platelet Inhibition by Negatively Interfering With an Active Metabolite: An Ex Vivo, In Vitro, and In Silico Study Abstract Abstract BACKGROUND: Prasugrel is converted into prasugrel active metabolite (PAM; R-138727) through the cytochrome P450–mediated conversion of an inter...
PMC11865102
core_pubmed_pmc
Assessing early therapeutic drug monitoring of adalimumab as a predictor of treatment efficacy and immunogenicity in rheumatic diseases: “early therapeutic drug monitoring of adalimumab”
Assessing early therapeutic drug monitoring of adalimumab as a predictor of treatment efficacy and immunogenicity in rheumatic diseases: “early therapeutic drug monitoring of adalimumab” Abstract Abstract Introduction Therapeutic drug monitoring (TDM) in inflammatory rheumatic diseases (RMDs) is gaining interest. Howev...
PMC11936814
core_pubmed_pmc
Bioequivalence of China- and Germany-manufactured bisoprolol (Concor ® ) tablets in fasted and fed healthy Chinese participants: a randomized, open-label, two-way, crossover study
Bioequivalence of China- and Germany-manufactured bisoprolol (Concor ® ) tablets in fasted and fed healthy Chinese participants: a randomized, open-label, two-way, crossover study Abstract Background The bioequivalence of Concor ® (Merck Healthcare KGaA, Darmstadt, Germany), a bisoprolol-containing tablet, manufactured...
PMC9834375
core_pubmed_pmc
Pharmacokinetics and Safety of Follitropin Delta in Gonadotropin Down-Regulated Healthy Chinese Women
Pharmacokinetics and Safety of Follitropin Delta in Gonadotropin Down-Regulated Healthy Chinese Women Abstract Background Follitropin delta, a novel recombinant follicle-stimulating hormone (rFSH) preparation derived from a human cell line, has different pharmacokinetic and pharmacodynamic properties compared with exis...
PMC5034953
core_pubmed_pmc
Population Pharmacokinetics and Pharmacodynamics of Lumefantrine in Young Ugandan Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria
Population Pharmacokinetics and Pharmacodynamics of Lumefantrine in Young Ugandan Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria Abstract Abstract Background. The pharmacokinetics and pharmacodynamics of lumefantrine, a component of the most widely used treatment for malaria, artemether-lumefan...
PMC12561088
core_pubmed_pmc
LLM-Enhanced Multimodal Framework for Drug–Drug Interaction Prediction
LLM-Enhanced Multimodal Framework for Drug–Drug Interaction Prediction Abstract Background: Drug–drug interactions (DDIs) involve pharmacokinetic or pharmacodynamic changes that occur when multiple drugs are co-administered, potentially leading to reduced efficacy or adverse effects. As polypharmacy becomes more preval...
PMC5752984
core_pubmed_pmc
A Pilot Study of Immune Activation and Rifampin Absorption in HIV-Infected Patients without Tuberculosis Infection: A Short Report
A Pilot Study of Immune Activation and Rifampin Absorption in HIV-Infected Patients without Tuberculosis Infection: A Short Report Abstract Abstract Background Rifampin malabsorption is frequently observed in tuberculosis patients coinfected with human immunodeficiency virus (HIV) but cannot be predicted by patient fac...
PMC5702903
core_pubmed_pmc
Predicting Drug Concentration‐Time Profiles in Multiple CNS Compartments Using a Comprehensive Physiologically‐Based Pharmacokinetic Model
Predicting Drug Concentration‐Time Profiles in Multiple CNS Compartments Using a Comprehensive Physiologically‐Based Pharmacokinetic Model Abstract Abstract Drug development targeting the central nervous system (CNS) is challenging due to poor predictability of drug concentrations in various CNS compartments. We develo...
PMC6219411
core_pubmed_pmc
Pharmacokinetic evaluation of a transdermal anastrozole-in-adhesive formulation
Pharmacokinetic evaluation of a transdermal anastrozole-in-adhesive formulation Abstract Background and objective Anastrozole is a well-established active pharmaceutical ingredient (API) used for the treatment of hormone-sensitive breast cancer (BC) in postmenopausal women. However, treatment with the only available or...
PMC4782683
core_pubmed_pmc
Extracorporeal treatment for carbamazepine poisoning: Systematic review and recommendations from the EXTRIP workgroup
Extracorporeal treatment for carbamazepine poisoning: Systematic review and recommendations from the EXTRIP workgroup Abstract Abstract Context . The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence and consensus-based recommendations on the use of extracorporeal treatments (ECT...
PMC7643733
core_pubmed_pmc
Model-Based Meta-analysis of Rifampicin Exposure and Mortality in Indonesian Tuberculous Meningitis Trials
Model-Based Meta-analysis of Rifampicin Exposure and Mortality in Indonesian Tuberculous Meningitis Trials Abstract Abstract Background Intensified antimicrobial treatment with higher rifampicin doses may improve outcome of tuberculous meningitis, but the desirable exposure and necessary dose are unknown. Our objective...
PMC4136845
core_pubmed_pmc
Evaluation of Antimalarial Activity and Toxicity of a New Primaquine Prodrug
Evaluation of Antimalarial Activity and Toxicity of a New Primaquine Prodrug Abstract Plasmodium vivax is the most prevalent of the five species causing malaria in humans. The current available treatment for P. vivax malaria is limited and unsatisfactory due to at least two drawbacks: the undesirable side effects of pr...
PMC11334799
core_pubmed_pmc
CG001, a C3b-targeted complement inhibitor, blocks 3 complement pathways: development and preclinical evaluation ∗
CG001, a C3b-targeted complement inhibitor, blocks 3 complement pathways: development and preclinical evaluation ∗ Abstract Key Points • The human-derived and antibody-like C3b-targeted fusion protein CG001 may simultaneously and effectively block 3 complement pathways. • CG001 holds high potential of further developme...
PMC12170689
core_pubmed_pmc
The dawn of a new era: can machine learning and large language models reshape QSP modeling?
The dawn of a new era: can machine learning and large language models reshape QSP modeling? Abstract Quantitative Systems Pharmacology (QSP) has emerged as a cornerstone of modern drug development, providing a robust framework to integrate data from preclinical and clinical studies, enhance decision-making, and optimiz...
PMC9610999
core_pubmed_pmc
Itraconazole-Induced Increases in Gilteritinib Exposure Are Mediated by CYP3A and OATP1B
Itraconazole-Induced Increases in Gilteritinib Exposure Are Mediated by CYP3A and OATP1B Abstract Gilteritinib, an FDA-approved tyrosine kinase inhibitor approved for the treatment of relapsed/refractory FLT3-mutated acute myeloid leukemia, is primarily eliminated via CYP3A4-mediated metabolism, a pathway that is sensi...
PMC11292196
core_pubmed_pmc
Comprehensive Target Engagement by the EZH2 Inhibitor Tulmimetostat Allows for Targeting of ARID1A Mutant Cancers
Comprehensive Target Engagement by the EZH2 Inhibitor Tulmimetostat Allows for Targeting of ARID1A Mutant Cancers Abstract Abstract Recurrent somatic mutations in the BRG1/BRM-associated factor (BAF) chromatin remodeling complex subunit ARID1A occur frequently in advanced urothelial, endometrial, and ovarian clear cell...
PMC5269655
core_pubmed_pmc
Discovery and Investigation of Natural Editing Function against Artificial Amino Acids in Protein Translation
Discovery and Investigation of Natural Editing Function against Artificial Amino Acids in Protein Translation Abstract Fluorine being not substantially present in the chemistry of living beings is an attractive element in tailoring novel chemical, biophysical, and pharmacokinetic properties of peptides and proteins. Th...
PMC7839485
core_pubmed_pmc
Continuous Learning in Model‐Informed Precision Dosing: A Case Study in Pediatric Dosing of Vancomycin
Continuous Learning in Model‐Informed Precision Dosing: A Case Study in Pediatric Dosing of Vancomycin Abstract Model‐informed precision dosing (MIPD) leverages pharmacokinetic (PK) models to tailor dosing to an individual patient’s needs, improving attainment of therapeutic drug exposure targets and thus potentially i...
PMC9258944
core_pubmed_pmc
On-Line Solid Phase Extraction High Performance Liquid Chromatography Method Coupled With Tandem Mass Spectrometry for the Therapeutic Monitoring of Cannabidiol and 7-Hydroxy-cannabidiol in Human Serum and Saliva
On-Line Solid Phase Extraction High Performance Liquid Chromatography Method Coupled With Tandem Mass Spectrometry for the Therapeutic Monitoring of Cannabidiol and 7-Hydroxy-cannabidiol in Human Serum and Saliva Abstract Cannabidiol is a novel antiseizure medication approved in Europe and the US for the treatment of s...
PMC5527615
core_pubmed_pmc
Linezolid Dose That Maximizes Sterilizing Effect While Minimizing Toxicity and Resistance Emergence for Tuberculosis
Linezolid Dose That Maximizes Sterilizing Effect While Minimizing Toxicity and Resistance Emergence for Tuberculosis Abstract ABSTRACT Linezolid has an excellent sterilizing effect in tuberculosis patients but high adverse event rates. The dose that would maximize efficacy and minimize toxicity is unknown. We performed...
PMC12497745
core_pubmed_pmc
Population pharmacokinetics modelling to predict DDI from zopiclone on clozapine in schizophrenia patients
Population pharmacokinetics modelling to predict DDI from zopiclone on clozapine in schizophrenia patients Abstract Introduction Clozapine, as a core drug for the treatment of schizophrenia, is widely used in the drug treatment of schizophrenia patients. However, when multiple drugs are used in combination, it is not c...
PMC6437231
core_pubmed_pmc
Population Pharmacokinetics of Semaglutide for Type 2 Diabetes
Population Pharmacokinetics of Semaglutide for Type 2 Diabetes Abstract Introduction The aim of the present analysis was to characterise the absorption, distribution and elimination of semaglutide by means of population pharmacokinetic (PK) models using data from nine clinical pharmacology trials conducted in both heal...
PMC11859217
core_pubmed_pmc
Compartment Model and Neural Network-Based Analysis of Combination Medication Ratios
Compartment Model and Neural Network-Based Analysis of Combination Medication Ratios Abstract Background: Combination medication strategies often involve complex interactions, making determining the appropriate pharmacodynamic component ratios challenging. Methods: This study established a time–dose relationship model ...
PMC6624146
core_pubmed_pmc
Pharmacokinetics and pharmacodynamics of natalizumab in pediatric patients with RRMS
Pharmacokinetics and pharmacodynamics of natalizumab in pediatric patients with RRMS Abstract Abstract Objective This phase I study investigated pharmacokinetic (PK) and pharmacodynamic (PD) profiles of natalizumab in pediatric patients with relapsing-remitting MS (RRMS). Methods Pediatric patients with RRMS who were p...
PMC6043562
core_pubmed_pmc
Relation of Prenatal Air Pollutant and Nutritional Exposures with Biomarkers of Allergic Disease in Adolescence
Relation of Prenatal Air Pollutant and Nutritional Exposures with Biomarkers of Allergic Disease in Adolescence Abstract Prenatal exposures may be critical for immune system development, with consequences for allergic disease susceptibility. We examined associations of prenatal exposures (nutrient intakes and air pollu...
PMC2996221
core_pubmed_pmc
An Assessment of the Interindividual Variability of Internal Dosimetry during Multi-Route Exposure to Drinking Water Contaminants
An Assessment of the Interindividual Variability of Internal Dosimetry during Multi-Route Exposure to Drinking Water Contaminants Abstract Abstract The objective of this study was to evaluate inter-individual variability in absorbed and internal doses after multi-route exposure to drinking water contaminants (DWC) in a...
PMC6717586
core_pubmed_pmc
Glucocorticoids and selumetinib are highly synergistic in RAS pathway-mutated childhood acute lymphoblastic leukemia through upregulation of BIM
Glucocorticoids and selumetinib are highly synergistic in RAS pathway-mutated childhood acute lymphoblastic leukemia through upregulation of BIM Abstract Abstract New drugs are needed for the treatment of relapsed acute lymphoblastic leukemia and preclinical evaluation of the MEK inhibitor, selumetinib, has shown that ...
PMC12672407
core_pubmed_pmc
Safety, Tolerability, and Pharmacokinetics of Galcanezumab, an Anti‐CGRP Antibody, in Healthy Chinese Participants
Safety, Tolerability, and Pharmacokinetics of Galcanezumab, an Anti‐CGRP Antibody, in Healthy Chinese Participants Abstract Abstract Galcanezumab is used in several regions, including the United States, Europe, and China, as a preventive treatment for migraine. This study aimed to evaluate the safety, tolerability, and...
PMC7682670
core_pubmed_pmc
Design and rationale of two phase 3 randomised controlled trials (COUGH-1 and COUGH-2) of gefapixant, a P2X3 receptor antagonist, in refractory or unexplained chronic cough
Design and rationale of two phase 3 randomised controlled trials (COUGH-1 and COUGH-2) of gefapixant, a P2X3 receptor antagonist, in refractory or unexplained chronic cough Abstract Background We present study designs, dose selection and preliminary patient characteristics from two phase 3 clinical trials of gefapixant...
PMC8426299
core_pubmed_pmc
Effect of severe renal impairment on the pharmacokinetics of brigatinib
Effect of severe renal impairment on the pharmacokinetics of brigatinib Abstract Abstract Background Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, targets activated, mutant forms of ALK and overcomes mechanisms of resistance to the ALK inhibitors crizotinib, ceritinib, and alectinib. Brigati...
PMC12804539
core_pubmed_pmc
In-silico assessment of phytochemical derivatives generated using CHEESE webserver for advancement of druggable candidate in pancreatic cancer therapy
In-silico assessment of phytochemical derivatives generated using CHEESE webserver for advancement of druggable candidate in pancreatic cancer therapy Abstract Abstract Research efforts for pancreatic cancer (PC) therapy has led to investigations of numerous therapeutic targets, yet there are still limited efficacy out...
PMC5617436
core_pubmed_pmc
Wogonoside inhibits IL-1β induced catabolism and hypertrophy in mouse chondrocyte and ameliorates murine osteoarthritis
Wogonoside inhibits IL-1β induced catabolism and hypertrophy in mouse chondrocyte and ameliorates murine osteoarthritis Abstract The inflammatory environment is correlated with extracellular matrix (ECM) degradation and chondrocyte hypertrophy in the development of osteoarthritis (OA). Previous studies have reported th...
PMC12066394
core_pubmed_pmc
Safety, Tolerability, and Pharmacokinetics of Single and Multiple Topical Applications of Sodium Taurodeoxycholate, a Treatment for Atopic Dermatitis
Safety, Tolerability, and Pharmacokinetics of Single and Multiple Topical Applications of Sodium Taurodeoxycholate, a Treatment for Atopic Dermatitis Abstract ABSTRACT Sodium taurodeoxycholate (TDCA) gel is a novel candidate for the treatment of atopic dermatitis and is currently under clinical development. TDCA is a t...
PMC7557242
core_pubmed_pmc
Novel Approach for Characterizing Propofol Binding Affinities to Serum Albumins from Different Species
Novel Approach for Characterizing Propofol Binding Affinities to Serum Albumins from Different Species Abstract Abstract The interaction between the main carrier (serum albumin, SA) of endogenous and exogenous compounds in the bloodstream of different species (human, bovine, canine, rat, rabbit, and sheep) and a genera...
PMC5684313
core_pubmed_pmc
Longrange PCR-based next-generation sequencing in pharmacokinetics and pharmacodynamics study of propofol among patients under general anaesthesia
Longrange PCR-based next-generation sequencing in pharmacokinetics and pharmacodynamics study of propofol among patients under general anaesthesia Abstract The individual response of patients to propofol results from the influence of genetic factors. However, the state of knowledge in this matter still remains insuffic...
PMC12541016
core_pubmed_pmc
Identification of stigmasterol derived AChE inhibitors for Alzheimer’s disease using high throughput virtual screening and molecular dynamics simulations
Identification of stigmasterol derived AChE inhibitors for Alzheimer’s disease using high throughput virtual screening and molecular dynamics simulations Abstract Abstract Alzheimer’s disease (AD), a progressive neurodegenerative disorder, poses a significant global health burden due to its intricate pathology and the ...
PMC10142039
core_pubmed_pmc
From Personalized to Precision Medicine in Oncology: A Model-Based Dosing Approach to Optimize Achievement of Imatinib Target Exposure
From Personalized to Precision Medicine in Oncology: A Model-Based Dosing Approach to Optimize Achievement of Imatinib Target Exposure Abstract Abstract Imatinib is a targeted cancer therapy that has significantly improved the care of patients with chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST...
PMC4984800
core_pubmed_pmc
A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies
A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies Abstract Abstract Background: The kinase activity of mTOR involves 2 multiprotein complexes, (mTORC1-mTORC2). Targeting mTORC1 with rapalogues induces compensatory feedback loops resulting in AKT/ERK a...
PMC11111785
core_pubmed_pmc
Quantifying combined effects of colistin and ciprofloxacin against Escherichia coli in an in silico pharmacokinetic-pharmacodynamic model
Quantifying combined effects of colistin and ciprofloxacin against Escherichia coli in an in silico pharmacokinetic-pharmacodynamic model Abstract Co-administering a low dose of colistin (CST) with ciprofloxacin (CIP) may improve the antibacterial effect against resistant Escherichia coli , offering an acceptable benef...
PMC9293327
core_pubmed_pmc
Exposure–Response Analyses for Therapeutic Dose Selection of Belantamab Mafodotin in Patients With Relapsed/Refractory Multiple Myeloma
Exposure–Response Analyses for Therapeutic Dose Selection of Belantamab Mafodotin in Patients With Relapsed/Refractory Multiple Myeloma Abstract Abstract Belantamab mafodotin is an antibody–drug conjugate comprising a humanized anti‐B‐cell maturation antigen (BCMA) monoclonal antibody conjugated to monomethyl auristati...
PMC8539586
core_pubmed_pmc
A Case of In Situ Phage Therapy against Staphylococcus aureus in a Bone Allograft Polymicrobial Biofilm Infection: Outcomes and Phage-Antibiotic Interactions
A Case of In Situ Phage Therapy against Staphylococcus aureus in a Bone Allograft Polymicrobial Biofilm Infection: Outcomes and Phage-Antibiotic Interactions Abstract Phage therapy (PT) shows promising potential in managing biofilm infections, which include refractory orthopedic infections. We report the case of a 13-y...
PMC12489687
core_pubmed_pmc
Pharmacokinetic Profiling and Tissue Distribution of Seven Key Saponins in Rats Following Oral Administration of Panacis Japonici Rhizoma Extracts
Pharmacokinetic Profiling and Tissue Distribution of Seven Key Saponins in Rats Following Oral Administration of Panacis Japonici Rhizoma Extracts Abstract Abstract The pharmacokinetics and distribution of natural compounds in living organisms are crucial to understanding their therapeutic potential and safety. In the ...
PMC10582335
core_pubmed_pmc
In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban
In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban Abstract Background: Almonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is commonly used as a first-line treatment for non-small cell lung cancer (N...
PMC11047535
core_pubmed_pmc
Pharmacokinetics and Nephrotoxicity of Polymyxin MRX-8 in Rats: A Novel Agent against Resistant Gram-Negative Bacteria
Pharmacokinetics and Nephrotoxicity of Polymyxin MRX-8 in Rats: A Novel Agent against Resistant Gram-Negative Bacteria Abstract Abstract MRX-8 is a novel polymyxin for carbapenem-resistant Gram-negative infections that has been recently evaluated in Phase I clinical trials. Herein, its pharmacokinetics (PK) and nephrot...
PMC5384962
core_pubmed_pmc
First-in-human studies of seletalisib, an orally bioavailable small-molecule PI3Kδ inhibitor for the treatment of immune and inflammatory diseases
First-in-human studies of seletalisib, an orally bioavailable small-molecule PI3Kδ inhibitor for the treatment of immune and inflammatory diseases Abstract Purpose PI3Ks are potential therapeutic targets in immune-inflammatory diseases. These studies aimed to investigate the safety, tolerability and PK profile of selet...
PMC4063799
core_pubmed_pmc
New orally active anticoagulant agents for the prevention and treatment of venous thromboembolism in cancer patients
New orally active anticoagulant agents for the prevention and treatment of venous thromboembolism in cancer patients Abstract Abstract Patients with cancer have a 6–7-fold higher risk of venous thromboembolism (VTE) as compared with non-cancer patients. Effective and safe anticoagulation for the prevention and treatmen...
PMC8584645
core_pubmed_pmc
NICLOSAMIDE-EXFOLIATED ANIONIC CLAY NANOHYBRID REPURPOSED AS AN ANTIVIRAL DRUG FOR TACKLING COVID-19; ORAL FORMULATION WITH TWEEN 60/EUDRAGIT S100
NICLOSAMIDE-EXFOLIATED ANIONIC CLAY NANOHYBRID REPURPOSED AS AN ANTIVIRAL DRUG FOR TACKLING COVID-19; ORAL FORMULATION WITH TWEEN 60/EUDRAGIT S100 Abstract Abstract The ongoing pandemic, COVID-19 (SARS-CoV-2), has afflicted millions of people around the world, necessitating that the scientific community work, diligentl...
PMC12625185
core_pubmed_pmc
Population Pharmacokinetics Modeling of Selpercatinib to Support Posology in Pediatric Patients With RET ‐Altered Metastatic Thyroid Cancer or Solid Tumors
Population Pharmacokinetics Modeling of Selpercatinib to Support Posology in Pediatric Patients With RET ‐Altered Metastatic Thyroid Cancer or Solid Tumors Abstract ABSTRACT Selpercatinib is a first‐in‐class, highly selective, RET kinase inhibitor with CNS activity, approved for the treatment of RET‐altered lung, thyro...
PMC10547630
core_pubmed_pmc
Is the One-Compartment Model with First Order Absorption a Useful Approximation?
Is the One-Compartment Model with First Order Absorption a Useful Approximation? Abstract Abstract Purpose The one-compartment model with first order absorption (ka1C) has been extensively used to fit oral data. But when the disposition parameters of the drug are not available, the bias in the parameter estimates remai...
PMC9095536
core_pubmed_pmc
Comparative Plasma and Interstitial Tissue Fluid Pharmacokinetics of Meropenem Demonstrate the Need for Increasing Dose and Infusion Duration in Obese and Non-obese Patients
Comparative Plasma and Interstitial Tissue Fluid Pharmacokinetics of Meropenem Demonstrate the Need for Increasing Dose and Infusion Duration in Obese and Non-obese Patients Abstract Background and Objectives A quantitative evaluation of the PK of meropenem, a broad-spectrum β-lactam antibiotic, in plasma and interstit...
PMC9780524
core_pubmed_pmc
Bioavailability of dissolved and crushed single tablets of bictegravir, emtricitabine, tenofovir alafenamide in healthy adults: the SOLUBIC randomized crossover study
Bioavailability of dissolved and crushed single tablets of bictegravir, emtricitabine, tenofovir alafenamide in healthy adults: the SOLUBIC randomized crossover study Abstract Abstract Background Crushing or dissolving bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) tablets is not recommended because ther...
PMC4811836
core_pubmed_pmc
Therapeutic Dose Monitoring for Linezolid in a Patient with MRSA Pneumonia with Bacteremia in Diabetes Insipidus
Therapeutic Dose Monitoring for Linezolid in a Patient with MRSA Pneumonia with Bacteremia in Diabetes Insipidus Abstract Introduction Few studies have investigated the effect of increased creatinine clearance (CrCl) on linezolid (LZD) concentration. Herein, we report the pharmacokinetic/pharmacodynamic (PK/PD) profile...
PMC8645831
core_pubmed_pmc
Delanzomib, a Novel Proteasome Inhibitor, Combined With Adalimumab Drastically Ameliorates Collagen-Induced Arthritis in Rats by Improving and Prolonging the Anti-TNF-α Effect of Adalimumab
Delanzomib, a Novel Proteasome Inhibitor, Combined With Adalimumab Drastically Ameliorates Collagen-Induced Arthritis in Rats by Improving and Prolonging the Anti-TNF-α Effect of Adalimumab Abstract Delanzomib is a novel proteasome inhibitor initially developed for treating multiple myeloma. It was found to inhibit the...
PMC9047970
core_pubmed_pmc
A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats
A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats Abstract Benzodiazepines potentiate respiratory depression when combined with an opioid leading the U.S Food and Drug Administration (FDA) to recommend updating the labels of these product...
PMC7970569
core_pubmed_pmc
Effect of Disease State on the Pharmacokinetics of Bedaquiline in Renal-Impaired and Diabetic Rats
Effect of Disease State on the Pharmacokinetics of Bedaquiline in Renal-Impaired and Diabetic Rats Abstract Bedaquiline (TMC-207) is a key anti-tubercular drug to fight against multidrug resistance tuberculosis. Little information is available till date on the impact of any disease state toward its pharmacokinetic beha...
PMC8847520
core_pubmed_pmc
Does Prolonged Infusion Time Really Improve the Efficacy of Meropenem Therapy? A Prospective Study in Critically Ill Patients
Does Prolonged Infusion Time Really Improve the Efficacy of Meropenem Therapy? A Prospective Study in Critically Ill Patients Abstract Introduction Meropenem is a carbapenem antibiotic, which has demonstrated excellent antimicrobial activity against gram-negative clinical isolates. It is also commonly used in criticall...
PMC9797969
core_pubmed_pmc
Evaluation of drug-drug interaction between rilpivirine and rifapentine using PBPK modelling
Evaluation of drug-drug interaction between rilpivirine and rifapentine using PBPK modelling Abstract Abstract Tuberculosis remains the leading cause of death among people living with HIV. Rifapentine is increasingly used to treat active disease or prevent reactivation, in both cases given either as weekly or daily the...
PMC7668473
core_pubmed_pmc
Population pharmacokinetics and dosing optimization of metformin in Chinese patients with type 2 diabetes mellitus
Population pharmacokinetics and dosing optimization of metformin in Chinese patients with type 2 diabetes mellitus Abstract Abstract Approximately 35% of patients fail to attain ideal initial blood glucose control under metformin monotherapy. The objective of this observational study is to simulate the optimal protocol...
PMC11263521
core_pubmed_pmc
Subcutaneous Levodopa: A New Engine for the Vintage Molecule
Subcutaneous Levodopa: A New Engine for the Vintage Molecule Abstract Abstract The management of Parkinson’s disease (PD) continues to evolve with advancements in non-oral levodopa-based therapies aiming to provide continuous drug delivery (CDD). Such therapies address the challenges posed by the emergence of motor flu...
PMC12298815
core_pubmed_pmc
Oral Metronomic Delivery of Atorvastatin and Docetaxel via Transporter-Targeted Nanoemulsions Enhances Antitumor Efficacy and Immune Modulation in Colon Cancer
Oral Metronomic Delivery of Atorvastatin and Docetaxel via Transporter-Targeted Nanoemulsions Enhances Antitumor Efficacy and Immune Modulation in Colon Cancer Abstract Abstract Background/Objectives : This study aimed to enhance the oral delivery and therapeutic synergy of atorvastatin (AT) and docetaxel (DT) through ...
PMC8216263
core_pubmed_pmc
Pharmacokinetics of gallic acid and protocatechuic acid in humans after dosing with Relinqing (RLQ) and the potential for RLQ-perpetrated drug–drug interactions on organic anion transporter (OAT) 1/3
Pharmacokinetics of gallic acid and protocatechuic acid in humans after dosing with Relinqing (RLQ) and the potential for RLQ-perpetrated drug–drug interactions on organic anion transporter (OAT) 1/3 Abstract Abstract Context Relinqing granules (RLQ) are being used alone or in combination with antibacterial drugs to tr...
PMC8938880
core_pubmed_pmc
Serial measurement of M. tuberculosis in blood from critically-ill patients with HIV-associated tuberculosis
Serial measurement of M. tuberculosis in blood from critically-ill patients with HIV-associated tuberculosis Abstract Summary Background Despite being highly prevalent in hospitalised patients with severe HIV-associated tuberculosis (TB) and sepsis, little is known about the mycobacteriology of Mycobacterium tuberculos...
PMC4065469
core_pubmed_pmc
Development of novel risperidone implants using blends of polycaprolactones and in vitro in vivo correlation studies
Development of novel risperidone implants using blends of polycaprolactones and in vitro in vivo correlation studies Abstract Abstract The objective of this study was to develop a novel implant containing risperidone intended for long-term treatment in Schizophrenia utilizing in vitro in vivo correlation (IVIVC) studie...
PMC10672599
core_pubmed_pmc
Drug Clearance in Patients with Inflammatory Bowel Disease Treated with Biologics
Drug Clearance in Patients with Inflammatory Bowel Disease Treated with Biologics Abstract Abstract Biological therapy is very effective for treating patients with moderate to severe inflammatory bowel disease (IBD). However, up to 40% can have primary non-response, and up to 50% of the patients can experience a loss o...
PMC7684313
core_pubmed_pmc
In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa
In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa Abstract Abstract The Cannabis sativa plant contains more than 120 cannabinoids. With the exceptions of ∆ 9 -tetrahydrocannabinol (∆ 9 -THC) and cannabidiol (CBD), comparatively little is known about the pharmacology of th...
PMC6068438
core_pubmed_pmc
Phase I safety and pharmacokinetic study of cipatinib, an original dual tyrosine kinase inhibitor
Phase I safety and pharmacokinetic study of cipatinib, an original dual tyrosine kinase inhibitor Abstract Background Cipatinib is a novel tyrosine kinase inhibitor against both EGFR and HER2/neu . This phase I trial was conducted to assess the safety, dose‐limiting toxicities (DLTs), and maximum‐tolerated dose of cipa...
PMC10289903
core_pubmed_pmc
A phase Ib study of adavosertib, a selective Wee1 inhibitor, in patients with locally advanced or metastatic solid tumors
A phase Ib study of adavosertib, a selective Wee1 inhibitor, in patients with locally advanced or metastatic solid tumors Abstract Abstract Adavosertib selectively inhibits Wee1, which regulates intra-S and G2/M cell-cycle checkpoints. This study investigated dosing schedules for adavosertib monotherapy, determining th...
PMC8520746
core_pubmed_pmc
Pharmacokinetic modeling of R and S‐Methadone and their metabolites to study the effects of various covariates in post‐operative children
Pharmacokinetic modeling of R and S‐Methadone and their metabolites to study the effects of various covariates in post‐operative children Abstract Abstract Methadone is a synthetic opioid used as an analgesic and for the treatment of opioid abuse disorder. The analgesic dose in the pediatric population is not well‐defi...
PMC10087065
core_pubmed_pmc
A mechanistic PK / PD model to enable dose selection of the potent anti‐tryptase antibody ( MTPS9579A ) in patients with moderate‐to‐severe asthma
A mechanistic PK / PD model to enable dose selection of the potent anti‐tryptase antibody ( MTPS9579A ) in patients with moderate‐to‐severe asthma Abstract Abstract Tryptase, a protease implicated in asthma pathology, is secreted from mast cells upon activation during an inflammatory allergic response. MTPS9579A is a n...
PMC12037183
core_pubmed_pmc
The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Subcutaneous Administration of a Novel Anti-NGF Monoclonal Antibody (AK115) in Healthy Participants: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase I Clinical Trial
The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Subcutaneous Administration of a Novel Anti-NGF Monoclonal Antibody (AK115) in Healthy Participants: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase I Clinical Trial Abstract Abstract Objective This study aimed to investigat...
PMC9335275
core_pubmed_pmc
A long-acting C-natriuretic peptide for achondroplasia
A long-acting C-natriuretic peptide for achondroplasia Abstract Significance The C-natriuretic peptide (CNP) analog vosoritide has recently been approved for the treatment of achondroplasia in children. However, the dosing regimen is burdensome, requiring daily subcutaneous injections in pediatric patients over multipl...
PMC11638133
core_pubmed_pmc
Dose‐exposure‐response of CARDALIS® (benazepril/spironolactone) on the classical and alternative arms of the renin‐angiotensin‐aldosterone system in healthy dogs
Dose‐exposure‐response of CARDALIS® (benazepril/spironolactone) on the classical and alternative arms of the renin‐angiotensin‐aldosterone system in healthy dogs Abstract Abstract Background Benazepril exhibits a dose‐dependent effect on biomarkers of the circulating renin‐angiotensin‐aldosterone system (RAAS) in dogs....