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PMC9255981
core_pubmed_pmc
Phase I Study of JNJ-74699157 in Patients with Advanced Solid Tumors Harboring the KRAS G12C Mutation
Phase I Study of JNJ-74699157 in Patients with Advanced Solid Tumors Harboring the KRAS G12C Mutation Abstract Abstract Background Patients with KRAS -mutant cancers have limited treatment options. Here we present a phase I study of JNJ-74699157, an oral, selective, covalent inhibitor of the KRAS G12C isoform, in patie...
PMC10256290
core_pubmed_pmc
Pharmacogenetic Testing and Therapeutic Drug Monitoring Of Sertraline at a Residential Treatment Center for Children and Adolescents: A Pilot Study
Pharmacogenetic Testing and Therapeutic Drug Monitoring Of Sertraline at a Residential Treatment Center for Children and Adolescents: A Pilot Study Abstract Abstract Background : Sertraline is commonly prescribed to children for the treatment of anxiety and major depressive disorder and is metabolized in part by CYP2C1...
PMC12780628
core_pubmed_pmc
Staged approach to overcome hyperbilirubinemia: tailored chemotherapy in liver metastases-a case report
Staged approach to overcome hyperbilirubinemia: tailored chemotherapy in liver metastases-a case report Abstract Background Hyperbilirubinemia presents a significant challenge in the treatment of patients with hepatic dysfunction, particularly those with metastatic liver disease requiring chemotherapy. Many chemotherap...
PMC11939487
core_pubmed_pmc
Antioxidant and Antidiabetic Potential of the Antarctic Lichen Gondwania regalis Ethanolic Extract: Metabolomic Profile and In Vitro and In Silico Evaluation
Antioxidant and Antidiabetic Potential of the Antarctic Lichen Gondwania regalis Ethanolic Extract: Metabolomic Profile and In Vitro and In Silico Evaluation Abstract Lichens are an important source of diverse and unique secondary metabolites with recognized biological activities through experimental and computational ...
PMC6933639
core_pubmed_pmc
Predicting the serum digoxin concentrations of infants in the neonatal intensive care unit through an artificial neural network
Predicting the serum digoxin concentrations of infants in the neonatal intensive care unit through an artificial neural network Abstract Background Given its narrow therapeutic range, digoxin’s pharmacokinetic parameters in infants are difficult to predict due to variation in birth weight and gestational age, especiall...
PMC10182161
core_pubmed_pmc
Vancomycin Clearance in Obese Adults is not Predictive of Clearance in Obese Adolescents
Vancomycin Clearance in Obese Adults is not Predictive of Clearance in Obese Adolescents Abstract Abstract Background and Objective Contradictory pharmacokinetic (PK) results have been observed between obese adults and obese adolescents, with absolute clearance (CL) reported to be either unaltered, lower, or higher in ...
PMC7268247
core_pubmed_pmc
Recent advances of novel technologies for quality consistency assessment of natural herbal medicines and preparations
Recent advances of novel technologies for quality consistency assessment of natural herbal medicines and preparations Abstract Abstract Quality consistency is one of the basic attributes of medicines, but it is also a difficult problem that natural medicines and their preparations must face. The complex chemical compos...
PMC12960056
core_pubmed_pmc
A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Fenebrutinib and Effect on the QT/QTc Interval in Healthy Participants
A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Fenebrutinib and Effect on the QT/QTc Interval in Healthy Participants Abstract ABSTRACT Fenebrutinib is a Bruton's tyrosine kinase inhibitor under investigation for the treatment of multiple sclerosis. The goal of this study was to investiga...
PMC9205298
core_pubmed_pmc
Double Dosing Levonorgestrel-Based Emergency Contraception for Individuals With Obesity
Double Dosing Levonorgestrel-Based Emergency Contraception for Individuals With Obesity Abstract Increasing the dose of levonorgestrel-containing emergency contraception from 1.5 mg to 3 mg did not improve rates of ovulation delay in individuals with obesity. Abstract OBJECTIVE: To assess whether dose escalation (ie, d...
PMC8124353
core_pubmed_pmc
Advances in Predictions of Oral Bioavailability of Candidate Drugs in Man with New Machine Learning Methodology
Advances in Predictions of Oral Bioavailability of Candidate Drugs in Man with New Machine Learning Methodology Abstract Oral bioavailability (F) is an essential determinant for the systemic exposure and dosing regimens of drug candidates. F is determined by numerous processes, and computational predictions of human es...
PMC12381318
core_pubmed_pmc
Evidence of Sex-Related Pharmacodynamic Differences in Photosensitive Epilepsy Treated with Valproate: Findings from a Retrospective, Observational, Single-Center, Within-Patient, Cohort Study
Evidence of Sex-Related Pharmacodynamic Differences in Photosensitive Epilepsy Treated with Valproate: Findings from a Retrospective, Observational, Single-Center, Within-Patient, Cohort Study Abstract Abstract Background and Objective Sexual dimorphism in drug efficacy, beyond pharmacokinetics (PK), remains underexplo...
PMC11984061
core_pubmed_pmc
A comprehensive review of Schisandra chinensis lignans: pharmacokinetics, pharmacological mechanisms, and future prospects in disease prevention and treatment
A comprehensive review of Schisandra chinensis lignans: pharmacokinetics, pharmacological mechanisms, and future prospects in disease prevention and treatment Abstract Lignans derived from Schisandra chinensis have attracted significant attention for their diverse pharmacological activities and clinical potential. This...
PMC12599904
core_pubmed_pmc
DeepTDM: Deep Learning-Based Prediction of Sequential Therapeutic Drug Monitoring Levels of Vancomycin
DeepTDM: Deep Learning-Based Prediction of Sequential Therapeutic Drug Monitoring Levels of Vancomycin Abstract Abstract Objective: Therapeutic drug monitoring (TDM) is essential for managing medication dosages in critically ill patients, particularly for antibiotics such as vancomycin. The dynamic physiological condit...
PMC12094827
core_pubmed_pmc
A Real-Time Plasma Concentration Prediction Model for Voriconazole in Elderly Patients via Machine Learning Combined with Population Pharmacokinetics
A Real-Time Plasma Concentration Prediction Model for Voriconazole in Elderly Patients via Machine Learning Combined with Population Pharmacokinetics Abstract Abstract Purpose Voriconazole (VCZ) is a first-line treatment for invasive fungal disease, characterized by a narrow therapeutic window and significant inter-ind...
PMC4206294
core_pubmed_pmc
Investigation of Cross-Species Translatability of Pharmacological MRI in Awake Nonhuman Primate - A Buprenorphine Challenge Study
Investigation of Cross-Species Translatability of Pharmacological MRI in Awake Nonhuman Primate - A Buprenorphine Challenge Study Abstract Background Pharmacological MRI (phMRI) is a neuroimaging technique where drug-induced hemodynamic responses can represent a pharmacodynamic biomarker to delineate underlying biologi...
PMC11605329
core_pubmed_pmc
Population pharmacokinetic study of the effect of polymorphisms in the ABCB1 and CES1 genes on the pharmacokinetics of dabigatran
Population pharmacokinetic study of the effect of polymorphisms in the ABCB1 and CES1 genes on the pharmacokinetics of dabigatran Abstract Purpose The impact of genetic polymorphisms in the ABCB1 and CES1 genes on dabigatran plasma concentrations remains a subject of debate, and the purpose of this study was to quantit...
PMC6930542
core_pubmed_pmc
Late-Stage Copper-Catalyzed Radiofluorination of an Arylboronic Ester Derivative of Atorvastatin
Late-Stage Copper-Catalyzed Radiofluorination of an Arylboronic Ester Derivative of Atorvastatin Abstract There is an unmet need for late-stage 18 F-fluorination strategies to label molecules with a wide range of relevant functionalities to medicinal chemistry, in particular (hetero)arenes, aiming to obtain unique in v...
PMC11078046
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Preclinical development of EXT608, an investigational parathyroid hormone derivative with extended half-life for the treatment of hypoparathyroidism
Preclinical development of EXT608, an investigational parathyroid hormone derivative with extended half-life for the treatment of hypoparathyroidism Abstract Abstract Hypoparathyroidism, a deficiency of parathyroid hormone (PTH), results in hypocalcemia, hyperphosphatemia, and hypercalciuria. The disease is poorly cont...
PMC7822342
core_pubmed_pmc
Clinical and pharmacokinetic/dynamic outcomes of prolonged infusions of beta-lactam antimicrobials: An overview of systematic reviews
Clinical and pharmacokinetic/dynamic outcomes of prolonged infusions of beta-lactam antimicrobials: An overview of systematic reviews Abstract Objective This overview of reviews aims to map and compare of objectives, methods, and findings of existing systematic reviews to develop a greater understanding of the informat...
PMC5599451
core_pubmed_pmc
Population pharmacokinetics of haloperidol in terminally ill adult patients
Population pharmacokinetics of haloperidol in terminally ill adult patients Abstract Purpose Over 80% of the terminally ill patients experience delirium in their final days. In the treatment of delirium, haloperidol is the drug of choice. Very little is known about the pharmacokinetics of haloperidol in this patient po...
PMC9843346
core_pubmed_pmc
Novel albendazole-glucan particles for enhancing intestinal absorption and improving hepatic targeting
Novel albendazole-glucan particles for enhancing intestinal absorption and improving hepatic targeting Abstract Abstract Background Glucan particles (GPs) are derived from the Saccharomyces cerevisiae cell wall. The hollow particles composed of β-1,3-D-glucan have been extensively studied in terms of immune regulation ...
PMC12237080
core_pubmed_pmc
The Impact of Drug Delivery Systems on Pharmacokinetics and Drug-Drug Interactions in Neuropsychiatric Treatment
The Impact of Drug Delivery Systems on Pharmacokinetics and Drug-Drug Interactions in Neuropsychiatric Treatment Abstract Neuropsychiatric drugs are essential for the management of mental health disorders, yet their therapeutic effectiveness is often compromised by complex pharmacokinetics (PK), significant drug-drug i...
PMC4178267
core_pubmed_pmc
Intra-Pleural Colistin Methanesulfonate Therapy for Pleural Infection caused by Carbapenem-Resistant Acinetobacter Baumannii: A Successful Case Report
Intra-Pleural Colistin Methanesulfonate Therapy for Pleural Infection caused by Carbapenem-Resistant Acinetobacter Baumannii: A Successful Case Report Abstract Infections caused by carbapenem-resistant, Gram-negative bacteria are an increasing clinical challenge, since the antimicrobial treatment options are often limi...
PMC6202475
core_pubmed_pmc
Predicting the Onset of Nonlinear Pharmacokinetics
Predicting the Onset of Nonlinear Pharmacokinetics Abstract When analyzing the pharmacokinetics ( PK ) of drugs, one is often faced with concentration C vs. time curves, which display a sharp transition at a critical concentration C crit . For C > C crit , the curve displays linear clearance and for C < C crit clearanc...
PMC5620575
core_pubmed_pmc
Comparative Pharmacokinetic Study for Linezolid and Two Novel Antibacterial Oxazolidinone Derivatives in Rabbits: Can Differences in the Pharmacokinetic Properties Explain the Discrepancies between Their In Vivo and In Vitro Antibacterial Activities?
Comparative Pharmacokinetic Study for Linezolid and Two Novel Antibacterial Oxazolidinone Derivatives in Rabbits: Can Differences in the Pharmacokinetic Properties Explain the Discrepancies between Their In Vivo and In Vitro Antibacterial Activities? Abstract This is a comparative pharmacokinetics study of linezolid (L...
PMC8349169
core_pubmed_pmc
Effects of delivery via pressure-adjustable pneumatic gas-powered dart gun of three antimicrobial drugs (ceftiofur crystalline free acid, tildopirosin, and tulathromycin) on drug disposition and meat quality in cattle
Effects of delivery via pressure-adjustable pneumatic gas-powered dart gun of three antimicrobial drugs (ceftiofur crystalline free acid, tildopirosin, and tulathromycin) on drug disposition and meat quality in cattle Abstract Abstract Background Although Beef Quality Assurance guidelines do not recommend use of dartin...
PMC8744126
core_pubmed_pmc
Hydroxychloroquine PK and exposure-response in pregnancies with lupus: the importance of adherence for neonatal outcomes
Hydroxychloroquine PK and exposure-response in pregnancies with lupus: the importance of adherence for neonatal outcomes Abstract Abstract Objective Evaluate the impact of pregnancy physiology and medication non-adherence on serum hydroxychloroquine (HCQ) pharmacokinetics (PK) and exposure-response in SLE. Methods We c...
PMC10044207
core_pubmed_pmc
Beta-Lactam Probability of Target Attainment Success: Cefepime as a Case Study
Beta-Lactam Probability of Target Attainment Success: Cefepime as a Case Study Abstract Abstract Introduction: Probability of target attainment (PTA) analysis using Monte Carlo simulations has become a mainstay of dose optimization. We highlight the technical and clinical factors that may affect PTA for beta-lactams. M...
PMC12654223
core_pubmed_pmc
Marine-Derived Natural Substances with Anticholinesterase Activity
Marine-Derived Natural Substances with Anticholinesterase Activity Abstract Alzheimer’s disease continues to be one of the most urgent neurodegenerative conditions, with acetylcholinesterase (AChE) inhibitors serving as a fundamental component of contemporary treatment approaches. Growing evidence underscores that mari...
PMC6202472
core_pubmed_pmc
Perspective on the State of Pharmacometrics and Systems Pharmacology Integration
Perspective on the State of Pharmacometrics and Systems Pharmacology Integration Abstract Abstract Reliance on modeling and simulation in drug discovery and development has dramatically increased over the past decade. Two disciplines at the forefront of this activity, pharmacometrics and systems pharmacology (SP), emer...
PMC9537531
core_pubmed_pmc
DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2
DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2 Abstract Monoclonal antibody therapy has played an important role against SARS-CoV-2. Strategies to deliver functional, antibody-based therapeutics with improved in vivo durability are needed to sup...
PMC6422316
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Modeling individual time courses of thrombopoiesis during multi-cyclic chemotherapy
Modeling individual time courses of thrombopoiesis during multi-cyclic chemotherapy Abstract Background Thrombocytopenia is a major side-effect of cytotoxic cancer therapies. The aim of precision medicine is to develop therapy modifications accounting for the individual’s risk. Methodology/Principle findings To solve t...
PMC6395397
core_pubmed_pmc
Modulation by Sigma-1 Receptor of Morphine Analgesia and Tolerance: Nociceptive Pain, Tactile Allodynia and Grip Strength Deficits During Joint Inflammation
Modulation by Sigma-1 Receptor of Morphine Analgesia and Tolerance: Nociceptive Pain, Tactile Allodynia and Grip Strength Deficits During Joint Inflammation Abstract Abstract Sigma-1 receptor antagonism increases the effects of morphine on nociceptive pain, even in morphine-tolerant animals. However, it is unknown whet...
PMC6966663
core_pubmed_pmc
Phase 1 Dose Escalation Study of the Allosteric AKT Inhibitor BAY 1125976 in Advanced Solid Cancer—Lack of Association between Activating AKT Mutation and AKT Inhibition-Derived Efficacy
Phase 1 Dose Escalation Study of the Allosteric AKT Inhibitor BAY 1125976 in Advanced Solid Cancer—Lack of Association between Activating AKT Mutation and AKT Inhibition-Derived Efficacy Abstract Abstract This open-label, phase I first-in-human study ( NCT01915576 ) of BAY 1125976, a highly specific and potent alloster...
PMC12655611
core_pubmed_pmc
In Silico Analysis of Serum Albumin Binding by Bone-Regenerative Hyaluronan-Based Molecules
In Silico Analysis of Serum Albumin Binding by Bone-Regenerative Hyaluronan-Based Molecules Abstract Abstract Background: The binding of glycosaminoglycans (GAG) to Wnt signaling components plays a key regulatory role in bone formation and regeneration. We previously reported de novo designed chemically modified hyalur...
PMC7437131
core_pubmed_pmc
A Pharmacokinetics‐Informed Approach to Navigating Hydroxychloroquine Shortages in Patients With Rheumatic Disease During the COVID‐19 Pandemic
A Pharmacokinetics‐Informed Approach to Navigating Hydroxychloroquine Shortages in Patients With Rheumatic Disease During the COVID‐19 Pandemic Abstract Abstract Objective The recent hydroxychloroquine (HCQ) shortage due to use in coronavirus disease 2019 (COVID‐19) has forced some rheumatic disease patients to choose ...
PMC5459318
core_pubmed_pmc
Phase I dose-escalation trial of intravaginal curcumin in women for cervical dysplasia
Phase I dose-escalation trial of intravaginal curcumin in women for cervical dysplasia Abstract Background This is a Phase I trial demonstrating safety and tolerability of intravaginal curcumin for future use in women with cervical neoplasia. Objective The objective of this study was to assess the safety, tolerability,...
PMC4590162
core_pubmed_pmc
Pharmacogenetics of analgesic drugs
Pharmacogenetics of analgesic drugs Abstract Summary points • Individual variability in pain perception and differences in the efficacy of analgesic drugs are complex phenomena and are partly genetically predetermined. • Analgesics act in various ways on the peripheral and central pain pathways and are regarded as one ...
PMC7771877
core_pubmed_pmc
A mechanistic framework for a priori pharmacokinetic predictions of orally inhaled drugs
A mechanistic framework for a priori pharmacokinetic predictions of orally inhaled drugs Abstract Abstract The fate of orally inhaled drugs is determined by pulmonary pharmacokinetic processes such as particle deposition, pulmonary drug dissolution, and mucociliary clearance. Even though each single process has been sy...
PMC12036438
core_pubmed_pmc
Representation Meets Optimization: Training PINNs and PIKANs for Gray-Box Discovery in Systems Pharmacology
Representation Meets Optimization: Training PINNs and PIKANs for Gray-Box Discovery in Systems Pharmacology Abstract Physics-Informed Kolmogorov–Arnold Networks (PIKANs) are gaining attention as an effective counterpart to the original multilayer perceptron-based Physics-Informed Neural Networks (PINNs). Both represent...
PMC8131856
core_pubmed_pmc
Progress in the Development of Anti-tissue Factor Pathway Inhibitors for Haemophilia Management
Progress in the Development of Anti-tissue Factor Pathway Inhibitors for Haemophilia Management Abstract Abstract The unprecedented progress in addressing unmet needs in haemophilia care to date includes developing several novel therapies that rebalance haemostasis by restoring thrombin generation in patients with haem...
PMC12823306
core_pubmed_pmc
Brain Amyloid Plaque Levels Affect Clinical Progression in Alzheimer Disease: Assessment of Amyloid PET and Change in CDR‐SB Utilizing Semi‐Mechanistic Model
Brain Amyloid Plaque Levels Affect Clinical Progression in Alzheimer Disease: Assessment of Amyloid PET and Change in CDR‐SB Utilizing Semi‐Mechanistic Model Abstract ABSTRACT Lecanemab is a humanized IgG1 monoclonal antibody binding with high affinity to protofibrils of amyloid‐beta (Aβ) protein. In clinical studies, ...
PMC12910638
core_pubmed_pmc
Mechanism‐Based Predictions of Local Tissue and Systemic Exposure for Drug Products Delivered Through the Female Reproductive Tract
Mechanism‐Based Predictions of Local Tissue and Systemic Exposure for Drug Products Delivered Through the Female Reproductive Tract Abstract Abstract Effective drug delivery through the female reproductive tract (FRT) presents unique challenges due to the lack of robust predictive models for drug exposure via this rout...
PMC7385621
core_pubmed_pmc
Combinations of common SNPs of the transporter gene ABCB1 influence apparent bioavailability, but not renal elimination of oral digoxin
Combinations of common SNPs of the transporter gene ABCB1 influence apparent bioavailability, but not renal elimination of oral digoxin Abstract Abstract Effects of different genotypes on the pharmacokinetics of probe substrates may support their use as phenotyping agents for the activity of the respective enzyme or tr...
PMC10651654
core_pubmed_pmc
Drug–drug interaction prediction of ziritaxestat using a physiologically based enzyme and transporter pharmacokinetic network interaction model
Drug–drug interaction prediction of ziritaxestat using a physiologically based enzyme and transporter pharmacokinetic network interaction model Abstract Abstract Ziritaxestat, an autotaxin inhibitor, was under development for the treatment of idiopathic pulmonary fibrosis. It is a substrate of cytochrome P450 3A4 (CYP3...
PMC10906727
core_pubmed_pmc
Pharmacokinetics, Pharmacodynamics, and Safety of Evocalcet (KHK7580), a Novel Calcimimetic Agent: An Open-Label, Single- and Multiple-Dose, Phase I Trial in Healthy Chinese Subjects
Pharmacokinetics, Pharmacodynamics, and Safety of Evocalcet (KHK7580), a Novel Calcimimetic Agent: An Open-Label, Single- and Multiple-Dose, Phase I Trial in Healthy Chinese Subjects Abstract Abstract Purpose This study explored the pharmacokinetics (PK), pharmacodynamics (PD), and safety of evocalcet (KHK7580), a new ...
PMC5774480
core_pubmed_pmc
Diminishing the side effect of mitomycin C by using pH-sensitive liposomes: in vitro characterization and in vivo pharmacokinetics
Diminishing the side effect of mitomycin C by using pH-sensitive liposomes: in vitro characterization and in vivo pharmacokinetics Abstract Introduction Mitomycin C is an anticancer antibiotic agent that has the potential for broad-spectrum use against several cancers, including mammary cancers. Because its half-life i...
PMC9732546
core_pubmed_pmc
In vivo efficacy assessment of the CDK4/6 inhibitor palbociclib and the PLK1 inhibitor volasertib in human chordoma xenografts
In vivo efficacy assessment of the CDK4/6 inhibitor palbociclib and the PLK1 inhibitor volasertib in human chordoma xenografts Abstract Background Management of advanced chordomas remains delicate considering their insensitivity to chemotherapy. Homozygous deletion of the regulatory gene CDKN2A has been described as th...
PMC6722552
core_pubmed_pmc
Human FcRn Tissue Expression Profile and Half-Life in PBMCs
Human FcRn Tissue Expression Profile and Half-Life in PBMCs Abstract System-wide quantitative characterization of human neonatal Fc receptor (FcRn) properties is critical for understanding and predicting human PK (pharmacokinetics) as well as the distribution of mAbs and Fc-fusion proteins using PBPK (physiologically-b...
PMC8597018
core_pubmed_pmc
Safety, tolerability, pharmacokinetics, pharmacodynamics, bioavailability and food effect of single doses of soticlestat in healthy subjects
Safety, tolerability, pharmacokinetics, pharmacodynamics, bioavailability and food effect of single doses of soticlestat in healthy subjects Abstract Abstract Aims Soticlestat is a first‐in‐class selective inhibitor of cholesterol 24‐hydroxylase, the enzyme that converts brain cholesterol to 24 S ‐hydroxycholesterol (2...
PMC8623090
core_pubmed_pmc
Cholesterol-Based Nanovesicles Enhance the In Vitro Cytotoxicity, Ex Vivo Intestinal Absorption, and In Vivo Bioavailability of Flutamide
Cholesterol-Based Nanovesicles Enhance the In Vitro Cytotoxicity, Ex Vivo Intestinal Absorption, and In Vivo Bioavailability of Flutamide Abstract Critical adverse effects and frequent administration, three times per day, limit the use of flutamide (FLT) as a chemotherapeutic agent in the treatment of prostate cancer. ...
PMC6379714
core_pubmed_pmc
Hydrophobicity drives the systemic distribution of lipid-conjugated siRNAs via lipid transport pathways
Hydrophobicity drives the systemic distribution of lipid-conjugated siRNAs via lipid transport pathways Abstract Abstract Efficient delivery of therapeutic RNA beyond the liver is the fundamental obstacle preventing its clinical utility. Lipid conjugation increases plasma half-life and enhances tissue accumulation and ...
PMC5602059
core_pubmed_pmc
Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib 400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers
Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib 400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers Abstract Background COX-2 inhibitors can be effective for acute migraine, but none is supplied in a rapidly absorbed, ready-to-use oral liquid formulation. DFN-15,...
PMC11944659
core_pubmed_pmc
Refined ADME Profiles for ATC Drug Classes
Refined ADME Profiles for ATC Drug Classes Abstract Abstract Background: Modern generative chemistry initiatives aim to produce potent and selective novel synthetically feasible molecules with suitable pharmacokinetic properties. General ranges of physicochemical properties relevant for the absorption, distribution, me...
PMC9136618
core_pubmed_pmc
The long-circulating effect of pegylated nanoparticles revisited via simultaneous monitoring of both the drug payloads and nanocarriers
The long-circulating effect of pegylated nanoparticles revisited via simultaneous monitoring of both the drug payloads and nanocarriers Abstract The long-circulating effect is revisited by simultaneous monitoring of the drug payloads and nanocarriers following intravenous administration of doxorubicin (DOX)-loaded meth...
PMC11435065
core_pubmed_pmc
Inhibition of P-Glycoprotein Asymmetrically Alters the In Vivo Exposure Profile of SGC003F: A Novel Guanylate Cyclase Stimulator
Inhibition of P-Glycoprotein Asymmetrically Alters the In Vivo Exposure Profile of SGC003F: A Novel Guanylate Cyclase Stimulator Abstract As a novel guanylate cyclase stimulator, SGC003F is being developed for the treatment of heart failure with a reduced ejection fraction (HFrEF). This study aimed to assess the effect...
PMC7316148
core_pubmed_pmc
Bupivacaine Pharmacokinetics and Breast Milk Excretion of Liposomal Bupivacaine Administered After Cesarean Birth
Bupivacaine Pharmacokinetics and Breast Milk Excretion of Liposomal Bupivacaine Administered After Cesarean Birth Abstract Very little plasma bupivacaine was transferred into breast milk after liposomal bupivacaine wound infiltration in patients who had undergone cesarean delivery. OBJECTIVE: To evaluate bupivacaine co...
PMC10342082
core_pubmed_pmc
Recent Advances of 68 Ga-Labeled PET Radiotracers with Nitroimidazole in the Diagnosis of Hypoxia Tumors
Recent Advances of 68 Ga-Labeled PET Radiotracers with Nitroimidazole in the Diagnosis of Hypoxia Tumors Abstract Abstract Positron emission tomography (PET) is a noninvasive molecular imaging method extensively applied in the detection and treatment of various diseases. Hypoxia is a common phenomenon found in most sol...
PMC12486802
core_pubmed_pmc
Cytomegalovirus prophylaxis with letermovir in pediatric (birth to <18 years of age) hematopoietic cell transplant recipients: pharmacokinetics, efficacy, and safety results of a Phase 2b study
Cytomegalovirus prophylaxis with letermovir in pediatric (birth to <18 years of age) hematopoietic cell transplant recipients: pharmacokinetics, efficacy, and safety results of a Phase 2b study Abstract ABSTRACT Letermovir, a cytomegalovirus (CMV) terminase complex inhibitor, was first approved for prophylaxis of CMV i...
PMC9774360
core_pubmed_pmc
Enhanced Bioavailability and Pharmacokinetics of a Natural Self-Emulsifying Reversible Hybrid-Hydrogel System of Quercetin: A Randomized Double-Blinded Comparative Crossover Study
Enhanced Bioavailability and Pharmacokinetics of a Natural Self-Emulsifying Reversible Hybrid-Hydrogel System of Quercetin: A Randomized Double-Blinded Comparative Crossover Study Abstract Despite the vast array of health beneficial pharmacological effects, the bioavailability of the dietary flavonoid quercetin was fou...
PMC5966352
core_pubmed_pmc
Enhancement of oral bioavailability of doxorubicin through surface modified biodegradable polymeric nanoparticles
Enhancement of oral bioavailability of doxorubicin through surface modified biodegradable polymeric nanoparticles Abstract Abstract Background Doxorubicin hydrochloride (DOX·HCl), an anthracycline glycoside antibiotic, exhibits low oral bioavailability due to active efflux from intestinal P-glycoprotein receptors. The ...
PMC6631493
core_pubmed_pmc
Polymeric Mesoporous Silica Nanoparticles for Enhanced Delivery of 5-Fluorouracil In Vitro
Polymeric Mesoporous Silica Nanoparticles for Enhanced Delivery of 5-Fluorouracil In Vitro Abstract Abstract There is a need for the improvement of conventional cancer treatment strategies by incorporation of targeted and non-invasive procedures aimed to reduce side-effects, drug resistance, and recurrent metastases. T...
PMC8099446
core_pubmed_pmc
Bench‐to‐bedside translation of chimeric antigen receptor (CAR) T cells using a multiscale systems pharmacokinetic‐pharmacodynamic model: A case study with anti‐BCMA CAR‐T
Bench‐to‐bedside translation of chimeric antigen receptor (CAR) T cells using a multiscale systems pharmacokinetic‐pharmacodynamic model: A case study with anti‐BCMA CAR‐T Abstract Abstract Despite tremendous success of chimeric antigen receptor (CAR) T cell therapy in clinical oncology, the dose‐exposure‐response rela...
PMC12532090
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SPARC: A Multipayload ADC Architecture for Programmable Drug Combinations
SPARC: A Multipayload ADC Architecture for Programmable Drug Combinations Abstract Drug combination is a cornerstone of modern medicine, particularly in oncology. However, drug combinations often fail due to poor disease site tropism and additive toxicities of composite drugs. Among targeted drug delivery systems for r...
PMC7913226
core_pubmed_pmc
A Physiologically-Based Pharmacokinetic Framework for Prediction of Drug Exposure in Malnourished Children
A Physiologically-Based Pharmacokinetic Framework for Prediction of Drug Exposure in Malnourished Children Abstract Malnutrition in children is a global health problem, particularly in developing countries. The effects of an insufficient supply of nutrients on body composition and physiological functions may have impli...
PMC10228170
core_pubmed_pmc
Biotransformation and brain distribution of the anti-COVID-19 drug molnupiravir and herb-drug pharmacokinetic interactions between the herbal extract Scutellaria formula-NRICM101
Biotransformation and brain distribution of the anti-COVID-19 drug molnupiravir and herb-drug pharmacokinetic interactions between the herbal extract Scutellaria formula-NRICM101 Abstract The aim of this study was to explore the effects of herbal drug pharmacokinetic interactions on the biotransformation of molnupiravi...
PMC4668334
core_pubmed_pmc
Pharmacokinetic Comparability of a Biosimilar Trastuzumab Anticipated from Its Physicochemical and Biological Characterization
Pharmacokinetic Comparability of a Biosimilar Trastuzumab Anticipated from Its Physicochemical and Biological Characterization Abstract Comparability between a biosimilar and its reference product requires the evaluation of critical quality attributes that may impact on its pharmacological response. Herein we present a...
PMC11134317
core_pubmed_pmc
Population pharmacokinetics and CD20 binding dynamics for mosunetuzumab in relapsed/refractory B‐cell non‐Hodgkin lymphoma
Population pharmacokinetics and CD20 binding dynamics for mosunetuzumab in relapsed/refractory B‐cell non‐Hodgkin lymphoma Abstract Abstract Mosunetuzumab (Mosun) is a CD20xCD3 T‐cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. The approved step‐up dose regimen of 1/2/60/30 mg IV...
PMC8359436
core_pubmed_pmc
Pharmacokinetics and Pharmacodynamics of Ertugliflozin in Healthy Japanese and Western Subjects
Pharmacokinetics and Pharmacodynamics of Ertugliflozin in Healthy Japanese and Western Subjects Abstract Abstract Ertugliflozin, a sodium‐glucose cotransporter 2 inhibitor, is approved for treatment of type 2 diabetes. This randomized, double‐blind (sponsor‐open) study in healthy Japanese subjects and open‐label study ...
PMC10898731
core_pubmed_pmc
A survey on the knowledge and attitudes of pharmacists towards the application of antimicrobial therapeutic drug monitoring and its challenges in Qatar
A survey on the knowledge and attitudes of pharmacists towards the application of antimicrobial therapeutic drug monitoring and its challenges in Qatar Abstract Introduction Therapeutic drug monitoring (TDM) is an integral part of pharmaceutical care. Antimicrobials are amongst the most commonly monitored medications. ...
PMC10747255
core_pubmed_pmc
CYP3A5*3 and CYP3A4*22 Cluster Polymorphism Effects on LCP-Tac Tacrolimus Exposure: Population Pharmacokinetic Approach
CYP3A5*3 and CYP3A4*22 Cluster Polymorphism Effects on LCP-Tac Tacrolimus Exposure: Population Pharmacokinetic Approach Abstract The aim of the study is to develop a population pharmacokinetic (PopPK) model and to investigate the influence of CYP3A5/CYP3A4 and ABCB1 single nucleotide polymorphisms (SNPs) on the Tacroli...
PMC11229278
core_pubmed_pmc
Epigallocatechin gallate and curcumin inhibit Bcl-2: a pharmacophore and docking based approach against cancer
Epigallocatechin gallate and curcumin inhibit Bcl-2: a pharmacophore and docking based approach against cancer Abstract The protein Bcl-2, well-known for its anti-apoptotic properties, has been implicated in cancer pathogenesis. Identifying the primary gene responsible for promoting improved cell survival and developme...
PMC8367929
core_pubmed_pmc
A minimal physiologically based pharmacokinetic model for high-dose methotrexate
A minimal physiologically based pharmacokinetic model for high-dose methotrexate Abstract Abstract Purpose High-dose methotrexate (HDMTX) is administered for the treatment of a variety of malignant tumors. Wide intra- and inter-individual variabilities characterize the pharmacokinetics of MTX, which is mostly excreted ...
PMC7995374
core_pubmed_pmc
Ampicillin pharmacokinetics in azotemic and healthy dogs
Ampicillin pharmacokinetics in azotemic and healthy dogs Abstract Abstract Background Little is known about effects of factors such as kidney disease, affecting ampicillin pharmacokinetics in dogs. Objectives Determine the pharmacokinetics of ampicillin after a single intravenous dose in healthy and azotemic dogs. Anim...
PMC4454220
core_pubmed_pmc
Population pharmacokinetics of methylphenidate hydrochloride extended-release multiple-layer beads in pediatric subjects with attention deficit hyperactivity disorder
Population pharmacokinetics of methylphenidate hydrochloride extended-release multiple-layer beads in pediatric subjects with attention deficit hyperactivity disorder Abstract A new multilayer-bead formulation of extended-release methylphenidate hydrochloride (MPH-MLR) has been evaluated in pharmacokinetic studies in h...
PMC5696486
core_pubmed_pmc
A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men
A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men Abstract Purpose This study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 215 with bevacizumab in healthy males. Methods In this randomized, single-b...
PMC5484552
core_pubmed_pmc
A Quantitative Systems Pharmacology Platform to Investigate the Impact of Alirocumab and Cholesterol-Lowering Therapies on Lipid Profiles and Plaque Characteristics
A Quantitative Systems Pharmacology Platform to Investigate the Impact of Alirocumab and Cholesterol-Lowering Therapies on Lipid Profiles and Plaque Characteristics Abstract Reduction in low-density lipoprotein cholesterol (LDL-C) is associated with decreased risk for cardiovascular disease. Alirocumab, an antibody to ...
PMC6681055
core_pubmed_pmc
Comparable Bioavailability and Disposition of Pefloxacin in Patients with Cystic Fibrosis and Healthy Volunteers Assessed via Population Pharmacokinetics
Comparable Bioavailability and Disposition of Pefloxacin in Patients with Cystic Fibrosis and Healthy Volunteers Assessed via Population Pharmacokinetics Abstract Quinolone antibiotics present an attractive oral treatment option in patients with cystic fibrosis (CF). Prior studies have reported comparable clearances an...
PMC12857956
core_pubmed_pmc
Uralenol, Glycyrol, and Abyssinone II as potent inhibitors of fibroblast growth factor receptor 2 from anti-cancer plants: A deep learning and molecular dynamics approach
Uralenol, Glycyrol, and Abyssinone II as potent inhibitors of fibroblast growth factor receptor 2 from anti-cancer plants: A deep learning and molecular dynamics approach Abstract Fibroblast Growth Factor Receptor 2 (FGFR2) plays a critical role in cellular proliferation and differentiation, and its dysregulation is as...
PMC4820942
core_pubmed_pmc
Efficacy of four commercially available heartworm preventive products against the JYD-34 laboratory strain of Dirofilaria immitis
Efficacy of four commercially available heartworm preventive products against the JYD-34 laboratory strain of Dirofilaria immitis Abstract Abstract Background Heartworm disease in dogs can be severe and life threatening. Resistance to available heartworm preventives was considered among potential causes of increased re...
PMC12705613
core_pubmed_pmc
Effects of gut microbiota dysbiosis on the metabolism and pharmacokinetics of losartan in rats: from endogenous to ceftriaxone-induced dysbiosis
Effects of gut microbiota dysbiosis on the metabolism and pharmacokinetics of losartan in rats: from endogenous to ceftriaxone-induced dysbiosis Abstract Introduction Gut microbiota plays a key role in drug metabolism. While gut microbiota dysbiosis is known to contribute to hypertension pathogenesis, its impact on dru...
PMC7080977
core_pubmed_pmc
Model-Based Biomarker Selection for Dose Individualization of Tyrosine-Kinase Inhibitors
Model-Based Biomarker Selection for Dose Individualization of Tyrosine-Kinase Inhibitors Abstract Tyrosine-kinase inhibitors (TKIs) demonstrate high inter-individual variability with respect to safety and efficacy and would therefore benefit from dose or schedule adjustments. This study investigated the efficacy, safet...
PMC10463362
core_pubmed_pmc
Pharmacodynamic and pharmacokinetic properties of the combined preparation of levothyroxine plus sustained- release liothyronine; a randomized controlled clinical trial
Pharmacodynamic and pharmacokinetic properties of the combined preparation of levothyroxine plus sustained- release liothyronine; a randomized controlled clinical trial Abstract Background Understanding pharmacokinetics (PK) and pharmacodynamics (PD) of the sustained-release liothyronine (SR-T3) is of paramount importa...
PMC5157781
core_pubmed_pmc
Effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in patients with Crohn's disease or ulcerative colitis who had failed conventional therapy
Effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in patients with Crohn's disease or ulcerative colitis who had failed conventional therapy Abstract Summary Background Adalimumab is approved for use in patients with moderate to severe Crohn's disease (CD) or ulcerative ...
PMC7527957
core_pubmed_pmc
Pre-clinical dose-ranging efficacy, pharmacokinetics, tissue biodistribution, and toxicity of a targeted contrast agent for MRI of amyloid deposition in Alzheimer’s disease
Pre-clinical dose-ranging efficacy, pharmacokinetics, tissue biodistribution, and toxicity of a targeted contrast agent for MRI of amyloid deposition in Alzheimer’s disease Abstract Abstract In these preclinical studies, we describe ADx-001 , an Aβ-targeted liposomal macrocyclic gadolinium (Gd) imaging agent, for MRI o...
PMC6930857
core_pubmed_pmc
Supervised Multidimensional Item Response Theory Modeling of Pediatric Iatrogenic Withdrawal Symptoms
Supervised Multidimensional Item Response Theory Modeling of Pediatric Iatrogenic Withdrawal Symptoms Abstract Item‐level data from composite scales can be analyzed with pharmacometric item response theory ( IRT ) models to improve the quantification of disease severity compared with the use of total composite scores. ...
PMC10368210
core_pubmed_pmc
Activity of Ivermectin and Its Metabolites against Asexual Blood Stage Plasmodium falciparum and Its Interactions with Antimalarial Drugs
Activity of Ivermectin and Its Metabolites against Asexual Blood Stage Plasmodium falciparum and Its Interactions with Antimalarial Drugs Abstract ABSTRACT Ivermectin is an endectocide used widely to treat a variety of internal and external parasites. Field trials of ivermectin mass drug administration for malaria tran...
PMC11564230
core_pubmed_pmc
Pharmacokinetic Properties of a Once-Weekly Fixed-Ratio Combination of Insulin Icodec and Semaglutide Compared with Separate Administration of Each Component in Individuals with Type 2 Diabetes Mellitus
Pharmacokinetic Properties of a Once-Weekly Fixed-Ratio Combination of Insulin Icodec and Semaglutide Compared with Separate Administration of Each Component in Individuals with Type 2 Diabetes Mellitus Abstract Background and Objective IcoSema is being developed as a subcutaneous once-weekly fixed-ratio combination of...
PMC5881162
core_pubmed_pmc
Application of Physiologically Based Pharmacokinetic (PBPK) Modeling Within a Bayesian Framework to Identify Poor Metabolizers of Efavirenz (PM), Using a Test Dose of Efavirenz
Application of Physiologically Based Pharmacokinetic (PBPK) Modeling Within a Bayesian Framework to Identify Poor Metabolizers of Efavirenz (PM), Using a Test Dose of Efavirenz Abstract Poor metabolisers of CYP2B6 (PM) require a lower dose of efavirenz because of serious adverse reactions resulting from the higher plas...
PMC7097682
core_pubmed_pmc
Safety and Pharmacokinetics of CXCR4 Peptide Antagonist, LY2510924, in Combination with Durvalumab in Advanced Refractory Solid Tumors
Safety and Pharmacokinetics of CXCR4 Peptide Antagonist, LY2510924, in Combination with Durvalumab in Advanced Refractory Solid Tumors Abstract Purpose: This was an open-label phase 1a study assessing the maximum tolerated dose (MTD), safety, and tolerability of CXCR4 peptide antagonist, LY2510924, administered in comb...
PMC6892276
core_pubmed_pmc
Metabolism of the dual FLT-3/Aurora kinase inhibitor CCT241736 in preclinical and human in vitro models: Implication for the choice of toxicology species
Metabolism of the dual FLT-3/Aurora kinase inhibitor CCT241736 in preclinical and human in vitro models: Implication for the choice of toxicology species Abstract CCT241736 is a dual fms-like tyrosine kinase 3 (FLT3)/Aurora kinase inhibitor in development for the treatment of acute myeloid leukaemia. The successful dev...
PMC8223438
core_pubmed_pmc
Preclinical Pharmacokinetics and Pharmacodynamics of Coptidis Preparation in Combination with Lovastatin in High-Fat Diet-Induced Hyperlipidemic Rats
Preclinical Pharmacokinetics and Pharmacodynamics of Coptidis Preparation in Combination with Lovastatin in High-Fat Diet-Induced Hyperlipidemic Rats Abstract Abstract Lovastatin is a standard therapy for dyslipidemia. Alternatively, some ethnomedicines, such as Coptidis preparation, have been used for the treatment of...
PMC9860980
core_pubmed_pmc
Pharmacokinetics and Pharmacodynamics (PK/PD) of Corallopyronin A against Methicillin-Resistant Staphylococcus aureus
Pharmacokinetics and Pharmacodynamics (PK/PD) of Corallopyronin A against Methicillin-Resistant Staphylococcus aureus Abstract Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is a World Health Organization’s high priority pathogen organism, with an estimated > 100,000 deaths worldwide in 2019. Thus, there i...
PMC11076063
core_pubmed_pmc
Comparison of Efficacy and Safety of a Bevacizumab Biosimilar, in Combination with Chemotherapies, in Nonresectable Metastatic Colorectal Cancer and in Advanced Nonsquamous Non–Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study
Comparison of Efficacy and Safety of a Bevacizumab Biosimilar, in Combination with Chemotherapies, in Nonresectable Metastatic Colorectal Cancer and in Advanced Nonsquamous Non–Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study Abstract Abstract Ranjith K. The objective of this study was to compare the...
PMC10635324
core_pubmed_pmc
A Multi-Site Phase I Trial of Veliparib with Standard Radiation and Temozolomide in Patients with Newly Diagnosed Glioblastoma Multiforme (GBM)
A Multi-Site Phase I Trial of Veliparib with Standard Radiation and Temozolomide in Patients with Newly Diagnosed Glioblastoma Multiforme (GBM) Abstract Purpose A multi-site Phase I trial was conducted to determine the safety, maximum tolerated dose, and pharmacokinetics (PK) of Veliparib, a Poly (ADP-ribose) polymeras...
PMC7238785
core_pubmed_pmc
How to manage KPC infections
How to manage KPC infections Abstract Abstract Carbapenemase-producing Enterobacteriaceae represent an increasing global threat worldwide and Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas. Risk stratifi...
PMC6342158
core_pubmed_pmc
Drug-Induced Acute Kidney Injury: A Standardized Patient Case for Clerkship Students
Drug-Induced Acute Kidney Injury: A Standardized Patient Case for Clerkship Students Abstract Abstract Introduction Drug-induced nephrotoxicity is a common yet preventable cause of acute renal failure. With the upward trend of prescription and over-the-counter medication use, it has become increasingly important for he...
PMC8831100
core_pubmed_pmc
Randomised controlled trial of intravenous nafamostat mesylate in COVID pneumonitis: Phase 1b/2a experimental study to investigate safety, Pharmacokinetics and Pharmacodynamics
Randomised controlled trial of intravenous nafamostat mesylate in COVID pneumonitis: Phase 1b/2a experimental study to investigate safety, Pharmacokinetics and Pharmacodynamics Abstract Summary Background Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharma...
PMC10287562
core_pubmed_pmc
Tau-targeting antisense oligonucleotide MAPT Rx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial
Tau-targeting antisense oligonucleotide MAPT Rx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial Abstract Tau plays a key role in Alzheimer’s disease (AD) pathophysiology, and accumulating evidence suggests that lowering tau may reduce this pathology. We sought to inhibit MAPT expression wi...
PMC10777827
core_pubmed_pmc
Pharmacokinetics and tolerability of cabotegravir and rilpivirine long-acting intramuscular injections to the vastus lateralis (lateral thigh) muscles of healthy adult participants
Pharmacokinetics and tolerability of cabotegravir and rilpivirine long-acting intramuscular injections to the vastus lateralis (lateral thigh) muscles of healthy adult participants Abstract ABSTRACT Cabotegravir + rilpivirine administered via intramuscular gluteal injections is the first complete long-acting (LA) regim...