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PMC11620482
core_pubmed_pmc
Phase 1 drug-drug interaction study to assess the effect of CYP3A4 inhibition and pan-CYP induction on the pharmacokinetics and safety of fosmanogepix in healthy participants
Phase 1 drug-drug interaction study to assess the effect of CYP3A4 inhibition and pan-CYP induction on the pharmacokinetics and safety of fosmanogepix in healthy participants Abstract ABSTRACT Immunocompromised patients are susceptible to fungal infections, and drug-drug interactions with antifungals may occur due to c...
PMC5702897
core_pubmed_pmc
Combining “Bottom‐up” and “Top‐down” Approaches to Assess the Impact of Food and Gastric pH on Pictilisib (GDC‐0941) Pharmacokinetics
Combining “Bottom‐up” and “Top‐down” Approaches to Assess the Impact of Food and Gastric pH on Pictilisib (GDC‐0941) Pharmacokinetics Abstract Pictilisib, a weakly basic compound, is an orally administered, potent, and selective pan‐inhibitor of phosphatidylinositol 3‐kinases for oncology indications. To investigate th...
PMC12486830
core_pubmed_pmc
Piperacillin reaches high concentrations in bile and target tissues of the biliary system: an experimental study in pigs
Piperacillin reaches high concentrations in bile and target tissues of the biliary system: an experimental study in pigs Abstract ABSTRACT The antibiotic combination of piperacillin/tazobactam (TZP) is commonly utilized for preventing and treating infections in the biliary system, with piperacillin being the primary ag...
PMC6572212
core_pubmed_pmc
Self-Nanoemulsifying Drug Delivery System (SNEDDS) for Improved Oral Bioavailability of Chlorpromazine: In Vitro and In Vivo Evaluation
Self-Nanoemulsifying Drug Delivery System (SNEDDS) for Improved Oral Bioavailability of Chlorpromazine: In Vitro and In Vivo Evaluation Abstract Abstract Background and Objectives: Lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions by modest adjustments and offer...
PMC9502080
core_pubmed_pmc
Adoption of Machine Learning in Pharmacometrics: An Overview of Recent Implementations and Their Considerations
Adoption of Machine Learning in Pharmacometrics: An Overview of Recent Implementations and Their Considerations Abstract Pharmacometrics is a multidisciplinary field utilizing mathematical models of physiology, pharmacology, and disease to describe and quantify the interactions between medication and patient. As these ...
PMC4228152
core_pubmed_pmc
The effect of the novel phosphodiesterase-4 inhibitor MEM 1414 on the allergen induced responses in mild asthma
The effect of the novel phosphodiesterase-4 inhibitor MEM 1414 on the allergen induced responses in mild asthma Abstract Background Inhaled allergen challenge is a standard method to study airway responses to inflammatory provocation and evaluate the therapeutic potential of novel anti-inflammatory compounds in asthma....
PMC5288521
core_pubmed_pmc
Pharmacokinetic and Toxicological Evaluation of a Zinc Gluconate-Based Chemical Sterilant Using In Vitro and In Silico Approaches
Pharmacokinetic and Toxicological Evaluation of a Zinc Gluconate-Based Chemical Sterilant Using In Vitro and In Silico Approaches Abstract Sclerosing agents as zinc gluconate-based chemical sterilants (Infertile®) are used for chemical castration. This solution is injected into the animal testis, but there are not enou...
PMC8443793
core_pubmed_pmc
Development, Testing, Parameterisation and Calibration of a Human PBPK Model for the Plasticiser, Di-(2-propylheptyl) Phthalate (DPHP) Using in Silico, in vitro and Human Biomonitoring Data
Development, Testing, Parameterisation and Calibration of a Human PBPK Model for the Plasticiser, Di-(2-propylheptyl) Phthalate (DPHP) Using in Silico, in vitro and Human Biomonitoring Data Abstract Abstract A physiologically based pharmacokinetic model for Di-(2-propylheptyl) phthalate (DPHP) was developed to interpre...
PMC11257205
core_pubmed_pmc
Determination of the anticancer activity of standardized extract of Centella asiatica (ECa 233) on cell growth and metastatic behavior in oral cancer cells
Determination of the anticancer activity of standardized extract of Centella asiatica (ECa 233) on cell growth and metastatic behavior in oral cancer cells Abstract Abstract Background and purpose: The anticancer drugs used for oral cancer treatment present many disadvantages, such as low solubility, low permeability, ...
PMC8286988
core_pubmed_pmc
A review on the pharmacokinetic properties and toxicity considerations for chloroquine and hydroxychloroquine to potentially treat coronavirus patients
A review on the pharmacokinetic properties and toxicity considerations for chloroquine and hydroxychloroquine to potentially treat coronavirus patients Abstract The SARS-CoV-2 virus, caused a novel emerged coronavirus disease, is growing rapidly worldwide. Few studies have evaluated the efficacy and safety of Chloroqui...
PMC10525963
core_pubmed_pmc
Conditionally Active, pH-Sensitive Immunoregulatory Antibodies Targeting VISTA and CTLA-4 Lead an Emerging Class of Cancer Therapeutics
Conditionally Active, pH-Sensitive Immunoregulatory Antibodies Targeting VISTA and CTLA-4 Lead an Emerging Class of Cancer Therapeutics Abstract Abstract Immune checkpoints and other immunoregulatory targets can be difficult to precisely target due to expression on non-tumor immune cells critical to maintaining immune ...
PMC10196431
core_pubmed_pmc
Mechanistic modeling of generic orally inhaled drug products: A workshop summary report
Mechanistic modeling of generic orally inhaled drug products: A workshop summary report Abstract Abstract In silico mechanistic modeling approaches have been designed by various stakeholders with the goal of supporting development and approval of generic orally inhaled drug products in the United States. This review su...
PMC7891441
core_pubmed_pmc
Evaluation of the Relationship of Glasdegib Exposure and Safety End Points in Patients With Refractory Solid Tumors and Hematologic Malignancies
Evaluation of the Relationship of Glasdegib Exposure and Safety End Points in Patients With Refractory Solid Tumors and Hematologic Malignancies Abstract Abstract Glasdegib is approved for treating acute myeloid leukemia in elderly patients at 100 mg once daily in combination with low‐dose cytarabine. Exposure‐efficacy...
PMC8402634
core_pubmed_pmc
Intranasal Administration of a Monoclonal Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection
Intranasal Administration of a Monoclonal Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection Abstract Abstract Despite the recent availability of vaccines against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an urgent need for specific anti-SARS-CoV-2 drugs. Monoclonal neutr...
PMC7988345
core_pubmed_pmc
Modeling of SARS-CoV-2 Treatment Effects for Informed Drug Repurposing
Modeling of SARS-CoV-2 Treatment Effects for Informed Drug Repurposing Abstract Several repurposed drugs are currently under investigation in the fight against coronavirus disease 2019 (COVID-19). Candidates are often selected solely by their effective concentrations in vitro , an approach that has largely not lived up...
PMC10525314
core_pubmed_pmc
Development and Validation of a High-Performance Liquid Chromatography with Tandem Mass Spectrometry (HPLC-MS/MS) Method for Quantification of Major Molnupiravir Metabolite (β-D-N4-hydroxycytidine) in Human Plasma
Development and Validation of a High-Performance Liquid Chromatography with Tandem Mass Spectrometry (HPLC-MS/MS) Method for Quantification of Major Molnupiravir Metabolite (β-D-N4-hydroxycytidine) in Human Plasma Abstract Molnupiravir is an antiviral drug against viral RNA polymerase activity approved by the FDA for t...
PMC8674004
core_pubmed_pmc
Regulatory utility of pharmacometrics in the development and evaluation of antimicrobial agents and its recent progress in China
Regulatory utility of pharmacometrics in the development and evaluation of antimicrobial agents and its recent progress in China Abstract Abstract Pharmacometrics is an emerging science that interprets drug, disease, and trial information in a mathematical fashion to inform and facilitate efficient drug development and...
PMC10532907
core_pubmed_pmc
Pharmacogenetic Variants Associated with Fluoxetine Pharmacokinetics from a Bioequivalence Study in Healthy Subjects
Pharmacogenetic Variants Associated with Fluoxetine Pharmacokinetics from a Bioequivalence Study in Healthy Subjects Abstract Fluoxetine is one of the most prescribed antidepressants, yet it still faces challenges due to high intersubject variability in patient response. Mainly metabolized by the highly polymorphic gen...
PMC7496554
core_pubmed_pmc
Population Pharmacokinetic/Pharmacodynamic Modeling of Glenzocimab (ACT017) a Glycoprotein VI Inhibitor of Collagen‐Induced Platelet Aggregation
Population Pharmacokinetic/Pharmacodynamic Modeling of Glenzocimab (ACT017) a Glycoprotein VI Inhibitor of Collagen‐Induced Platelet Aggregation Abstract Abstract Glenzocimab (ACT017) is a humanized monoclonal antigen‐binding fragment (Fab) directed against the human platelet glycoprotein VI, a key receptor for collage...
PMC6407737
core_pubmed_pmc
Phase I Study of the Focal Adhesion Kinase Inhibitor BI 853520 in Japanese and Taiwanese Patients with Advanced or Metastatic Solid Tumors
Phase I Study of the Focal Adhesion Kinase Inhibitor BI 853520 in Japanese and Taiwanese Patients with Advanced or Metastatic Solid Tumors Abstract Abstract Background Focal adhesion kinase (FAK) inhibitors have demonstrated anti-tumor activity preclinically and are currently being evaluated in humans. A first-in-human...
PMC12511766
core_pubmed_pmc
Pharmacokinetics, safety and tolerability of ipatasertib in combination with palbociclib and fulvestrant in patients with advanced breast cancer in a phase Ib study
Pharmacokinetics, safety and tolerability of ipatasertib in combination with palbociclib and fulvestrant in patients with advanced breast cancer in a phase Ib study Abstract Introduction Ipatasertib is a potent, highly selective, small molecule AKT inhibitor that has been evaluated in combination with palbociclib and f...
PMC7719393
core_pubmed_pmc
Systemic Lupus Erythematosus Activity Affects the Sinusoidal Uptake Transporter OATP1B1 Evaluated by the Pharmacokinetics of Atorvastatin
Systemic Lupus Erythematosus Activity Affects the Sinusoidal Uptake Transporter OATP1B1 Evaluated by the Pharmacokinetics of Atorvastatin Abstract Abstract The present study assessed the effect of systemic lupus erythematosus (SLE) activity, a chronic and inflammatory autoimmune disease, on the sinusoidal uptake transp...
PMC4143601
core_pubmed_pmc
Phase I dose-escalation study of the HSP90 inhibitor AUY922 in Japanese patients with advanced solid tumors
Phase I dose-escalation study of the HSP90 inhibitor AUY922 in Japanese patients with advanced solid tumors Abstract Purpose AUY922 is a potent non-geldanamycin inhibitor of heat-shock protein 90. This study was carried out in Japanese patients to determine the maximum tolerated dose (MTD), and to characterize safety, ...
PMC10393585
core_pubmed_pmc
Pharmacokinetics of Apixaban Among Peritoneal Dialysis Patients
Pharmacokinetics of Apixaban Among Peritoneal Dialysis Patients Abstract Abstract Rationale & Objective The efficacy and safety profile of apixaban remains uncertain in patients receiving peritoneal dialysis (PD) despite increasing use in this population. Accordingly, we assessed the pharmacokinetics of apixaban among ...
PMC9099122
core_pubmed_pmc
Effects of elagolix on the pharmacokinetics of omeprazole and its metabolites in healthy premenopausal women
Effects of elagolix on the pharmacokinetics of omeprazole and its metabolites in healthy premenopausal women Abstract Abstract This study evaluated the effect of repeated doses of elagolix on the pharmacokinetics (PK) of omeprazole and its metabolites in healthy premenopausal female subjects. Adult premenopausal female...
PMC3978604
core_pubmed_pmc
Selective inhibition of spleen tyrosine kinase (SYK) with a novel orally bioavailable small molecule inhibitor, RO9021, impinges on various innate and adaptive immune responses: implications for SYK inhibitors in autoimmune disease therapy
Selective inhibition of spleen tyrosine kinase (SYK) with a novel orally bioavailable small molecule inhibitor, RO9021, impinges on various innate and adaptive immune responses: implications for SYK inhibitors in autoimmune disease therapy Abstract Abstract Introduction Spleen tyrosine kinase (SYK) is a key integrator ...
PMC8694721
core_pubmed_pmc
The effects of linalool acupoint application therapy on sleep regulation
The effects of linalool acupoint application therapy on sleep regulation Abstract Abstract The Shenque acupoint is located in the umbilicus of the human body. In the human body meridians, the Shenque acupoint can regulate body functions. The Shenque acupoint was one of the important acupuncture acupoints for the treatm...
PMC11768525
core_pubmed_pmc
Curcumin-Based Nanoparticles: Advancements and Challenges in Tumor Therapy
Curcumin-Based Nanoparticles: Advancements and Challenges in Tumor Therapy Abstract Abstract Curcumin, a bioactive compound derived from the rhizome of Curcuma longa L., has garnered significant attention for its potent anticancer properties. Despite its promising therapeutic potential, its poor bioavailability, rapid ...
PMC6070450
core_pubmed_pmc
The tetraamine chelator outperforms HYNIC in a new technetium-99m-labelled somatostatin receptor 2 antagonist
The tetraamine chelator outperforms HYNIC in a new technetium-99m-labelled somatostatin receptor 2 antagonist Abstract Abstract Background Somatostatin receptor targeting radiopeptides are successfully being used to image, stage, and monitor patients with neuroendocrine tumours. They are exclusively agonists that inter...
PMC7070793
core_pubmed_pmc
Safety, Tolerability, and Pharmacokinetics of the Mineralocorticoid Receptor Modulator AZD9977 in Healthy Men: A Phase I Multiple Ascending Dose Study
Safety, Tolerability, and Pharmacokinetics of the Mineralocorticoid Receptor Modulator AZD9977 in Healthy Men: A Phase I Multiple Ascending Dose Study Abstract Excessive activation of the mineralocorticoid receptor (MR) underlies the pathophysiology of heart failure and chronic kidney disease. Hyperkalemia risk limits ...
PMC8536414
core_pubmed_pmc
The LC-MS/MS-Based Measurement of Isopimaric Acid in Rat Plasma and Application of Pharmacokinetics
The LC-MS/MS-Based Measurement of Isopimaric Acid in Rat Plasma and Application of Pharmacokinetics Abstract Abstract Isopimaric acid (IPA) exhibits a diverse array of pharmacological activities, having been shown to function as an antihypertensive, antitumor, antibacterial, and hypocholesterolemic agent. However, few ...
PMC12151664
core_pubmed_pmc
First-in-class intranasal epinephrine spray for anaphylaxis: Dose finding clinical study
First-in-class intranasal epinephrine spray for anaphylaxis: Dose finding clinical study Abstract Background Anaphylaxis is a life-threatening clinical presentation of acute systemic allergic reactions. Timely administration of epinephrine, usually by intramuscular autoinjector, is a robust life-saving treatment. Despi...
PMC11402398
core_pubmed_pmc
Plug-and-play nucleic acid-mediated multimerization of biparatopic nanobodies for molecular imaging
Plug-and-play nucleic acid-mediated multimerization of biparatopic nanobodies for molecular imaging Abstract Abstract In cancer molecular imaging, selecting binders with high specificity and affinity for biomarkers is paramount for achieving high-contrast imaging within clinical time frames. Nanobodies have emerged as ...
PMC12265020
core_pubmed_pmc
Donanemab exposure‐response in early symptomatic Alzheimer's disease
Donanemab exposure‐response in early symptomatic Alzheimer's disease Abstract Abstract INTRODUCTION These analyses aimed to identify factors impacting donanemab exposure, amyloid plaque, and clinical efficacy in early symptomatic Alzheimer's disease using a population pharmacokinetic/pharmacodynamic (PK/PD) approach. M...
PMC8628514
core_pubmed_pmc
Glycoengineering of Therapeutic Antibodies with Small Molecule Inhibitors
Glycoengineering of Therapeutic Antibodies with Small Molecule Inhibitors Abstract Monoclonal antibodies (mAbs) are one of the cornerstones of modern medicine, across an increasing range of therapeutic areas. All therapeutic mAbs are glycoproteins, i.e., their polypeptide chain is decorated with glycans, oligosaccharid...
PMC10192568
core_pubmed_pmc
Comparison of pharmacokinetic profiles of seven major bioactive components in normal and non-alcoholic fatty liver disease (NAFLD) rats after oral administration of Ling-Gui-Zhu-Gan decoction by UPLC-MS/MS
Comparison of pharmacokinetic profiles of seven major bioactive components in normal and non-alcoholic fatty liver disease (NAFLD) rats after oral administration of Ling-Gui-Zhu-Gan decoction by UPLC-MS/MS Abstract Abstract A sensitive and rapid ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/...
PMC8368853
core_pubmed_pmc
The varying effects of antibiotics on gut microbiota
The varying effects of antibiotics on gut microbiota Abstract Abstract Antibiotics are lifesaving therapeutic drugs that have been used by human for decades. They are used both in the fight against bacterial pathogens for both human and for animal feeding. However, of recent, their effects on the gut microbial composit...
PMC11732010
core_pubmed_pmc
Drug-resistant bacteria in the critically ill: patterns and mechanisms of resistance and potential remedies
Drug-resistant bacteria in the critically ill: patterns and mechanisms of resistance and potential remedies Abstract Antimicrobial resistance in the intensive care unit is an ongoing global healthcare concern associated with high mortality and morbidity rates and high healthcare costs. Select groups of bacterial pathog...
PMC11960066
core_pubmed_pmc
The tradeoffs between persistence and mutation rates at sub-inhibitory antibiotic concentrations in Staphylococcus aureus
The tradeoffs between persistence and mutation rates at sub-inhibitory antibiotic concentrations in Staphylococcus aureus Abstract ABSTRACT The rational design of the antibiotic treatment of bacterial infections employs these drugs to reach concentrations that exceed the minimum needed to prevent the replication of the...
PMC3850926
core_pubmed_pmc
Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose
Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose Abstract Background The receptor kinase inhibitor toceranib phosphate (Palladia) was approved for use in dogs in 2009 using a dose of 3.25 mg/kg administer...
PMC9704087
core_pubmed_pmc
Solid lipid nanoparticle as an effective drug delivery system of a novel curcumin derivative: formulation, release in vitro and pharmacokinetics in vivo
Solid lipid nanoparticle as an effective drug delivery system of a novel curcumin derivative: formulation, release in vitro and pharmacokinetics in vivo Abstract Abstract Context Curcumin (Cur) has a short duration of action which limits its therapeutic efficacy. Carbonic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3...
PMC3525665
core_pubmed_pmc
SLC22A1-ABCB1 Haplotype Profiles Predict Imatinib Pharmacokinetics in Asian Patients with Chronic Myeloid Leukemia
SLC22A1-ABCB1 Haplotype Profiles Predict Imatinib Pharmacokinetics in Asian Patients with Chronic Myeloid Leukemia Abstract Objective This study aimed to explore the influence of SLC22A1, PXR, ABCG2, ABCB1 and CYP3A5*3 genetic polymorphisms on imatinib mesylate (IM) pharmacokinetics in Asian patients with chronic myelo...
PMC11434833
core_pubmed_pmc
Pharmacokinetics of Piperacillin–Tazobactam in Critically Ill Patients with Open Abdomen and Vacuum-Assisted Wound Closure: Dosing Considerations Using Monte Carlo Simulation
Pharmacokinetics of Piperacillin–Tazobactam in Critically Ill Patients with Open Abdomen and Vacuum-Assisted Wound Closure: Dosing Considerations Using Monte Carlo Simulation Abstract Abstract Background: Open abdomen with vacuum-assisted wound closure therapy (OA/VAC) is frequently used in critically ill patients alth...
PMC8248099
core_pubmed_pmc
Phase 1 Renal Impairment Trial Results Supports Targeted Individualized Dosing of ELX‐02 in Patients With Nephropathic Cystinosis
Phase 1 Renal Impairment Trial Results Supports Targeted Individualized Dosing of ELX‐02 in Patients With Nephropathic Cystinosis Abstract Abstract The aim of this study was to assess the pharmacokinetics (PK) and safety of ELX‐02 in a renally impaired population and apply these findings to the individualized dosing of...
PMC5055303
core_pubmed_pmc
Identification and Tumour-Binding Properties of a Peptide with High Affinity to the Disialoganglioside GD2
Identification and Tumour-Binding Properties of a Peptide with High Affinity to the Disialoganglioside GD2 Abstract Neuroectodermal tumours are characterized by aberrant processing of disialogangliosides concomitant with high expression of GD2 or GD3 on cell surfaces. Antibodies targeting GD2 are already in clinical us...
PMC3416976
core_pubmed_pmc
A multicenter, open-label, efficacy, pharmacokinetic, and safety study of adalimumab in Japanese patients with ankylosing spondylitis
A multicenter, open-label, efficacy, pharmacokinetic, and safety study of adalimumab in Japanese patients with ankylosing spondylitis Abstract We evaluated the efficacy, pharmacokinetics, and safety of adalimumab in Japanese patients with active ankylosing spondylitis (AS) who had an inadequate response to, or who were...
PMC6278136
core_pubmed_pmc
Pharmacokinetics of rivaroxaban in children using physiologically based and population pharmacokinetic modelling: an EINSTEIN-Jr phase I study
Pharmacokinetics of rivaroxaban in children using physiologically based and population pharmacokinetic modelling: an EINSTEIN-Jr phase I study Abstract Background The EINSTEIN-Jr program will evaluate rivaroxaban for the treatment of venous thromboembolism (VTE) in children, targeting exposures similar to the 20 mg onc...
PMC7171252
core_pubmed_pmc
Pharmacokinetics, mass balance, tissue distribution, metabolism, and excretion of praliciguat, a clinical‐stage soluble guanylate cyclase stimulator in rats
Pharmacokinetics, mass balance, tissue distribution, metabolism, and excretion of praliciguat, a clinical‐stage soluble guanylate cyclase stimulator in rats Abstract Abstract The pharmacokinetics (PK), metabolism, excretion, mass balance, and tissue distribution of [ 14 C]praliciguat were evaluated following oral admin...
PMC6245886
core_pubmed_pmc
Expanding behavior pattern sensitivity analysis with model selection and survival analysis
Expanding behavior pattern sensitivity analysis with model selection and survival analysis Abstract Abstract Background Sensitivity analysis is an essential step in mathematical modeling because it identifies parameters with a strong influence on model output, due to natural variation or uncertainty in the parameter va...
PMC5443883
core_pubmed_pmc
Developing the Totality of Evidence for Biosimilars: Regulatory Considerations and Building Confidence for the Healthcare Community
Developing the Totality of Evidence for Biosimilars: Regulatory Considerations and Building Confidence for the Healthcare Community Abstract Biosimilars are highly similar versions of approved branded biologics. Unlike generics, they are not exact replicas of reference products. Minor differences between biosimilars an...
PMC12784657
core_pubmed_pmc
Pharmacologic Targeting of miR29b with Bortezomib and Sorafenib to Improve Decitabine Sensitivity in Patients with Acute Myeloid Leukemia: Results from a Phase 1 Dose-Escalation Trial
Pharmacologic Targeting of miR29b with Bortezomib and Sorafenib to Improve Decitabine Sensitivity in Patients with Acute Myeloid Leukemia: Results from a Phase 1 Dose-Escalation Trial Abstract Simple Summary Decitabine is a commonly used drug for acute myeloid leukemia (AML), an aggressive blood cancer, but it does not...
PMC12841350
core_pubmed_pmc
Evaluation of Vortioxetine on Global DNA Methylation in Maternal and Offspring Rats and In Silico Molecular Docking to Key Epigenetic Enzymes
Evaluation of Vortioxetine on Global DNA Methylation in Maternal and Offspring Rats and In Silico Molecular Docking to Key Epigenetic Enzymes Abstract Mothers face high depression risks during pregnancy, and untreated depression can harm both mother and baby. Vortioxetine is a novel antidepressant with a multimodal mec...
PMC8966651
core_pubmed_pmc
PKPD Modeling of the Inoculum Effect of Acinetobacter baumannii on Polymyxin B in vivo
PKPD Modeling of the Inoculum Effect of Acinetobacter baumannii on Polymyxin B in vivo Abstract Abstract The reduction in antimicrobial activity at high bacterial counts is a microbiological phenomenon known as the inoculum effect (IE). In a previous in vitro study, a significant IE was observed for polymyxin B (PMB) a...
PMC10707387
core_pubmed_pmc
Illicium verum L. (Star Anise) Essential Oil: GC/MS Profile, Molecular Docking Study, In Silico ADME Profiling, Quorum Sensing, and Biofilm-Inhibiting Effect on Foodborne Bacteria
Illicium verum L. (Star Anise) Essential Oil: GC/MS Profile, Molecular Docking Study, In Silico ADME Profiling, Quorum Sensing, and Biofilm-Inhibiting Effect on Foodborne Bacteria Abstract Abstract Illicium verum , or star anise, has many uses ranging from culinary to religious. It has been used in the food industry si...
PMC11754044
core_pubmed_pmc
UGT2B15 single nucleotide polymorphism reduces dabigatran acylglucuronide formation in humans
UGT2B15 single nucleotide polymorphism reduces dabigatran acylglucuronide formation in humans Abstract Background Dabigatran etexilate (DABE), a prodrug of dabigatran (DAB), is a direct thrombin inhibitor used to prevent ischemic stroke and thromboembolism during atrial fibrillation. The effect of genetic polymorphisms...
PMC12896389
core_pubmed_pmc
A Combined Model‐Based Meta‐Analysis of Aggregated and Individual FEV1 Data From Randomized COPD Trials
A Combined Model‐Based Meta‐Analysis of Aggregated and Individual FEV1 Data From Randomized COPD Trials Abstract ABSTRACT Model‐based meta‐analysis allows integration of aggregated‐level data (AD) from different clinical trials in one model to assess population efficacy/safety. However, AD is limited in individual‐leve...
PMC7064984
core_pubmed_pmc
Low‐dose empagliflozin as adjunct‐to‐insulin therapy in type 1 diabetes: A valid modelling and simulation analysis to confirm efficacy
Low‐dose empagliflozin as adjunct‐to‐insulin therapy in type 1 diabetes: A valid modelling and simulation analysis to confirm efficacy Abstract Abstract Aim To confirm the observed reduction in HbA1c for the 2.5 mg dose in EASE‐3 by modelling and simulation analyses. Materials and methods Independent of data from EASE‐...
PMC6058678
core_pubmed_pmc
Multiseed liposomal drug delivery system using micelle gradient as driving force to improve amphiphilic drug retention and its anti-tumor efficacy
Multiseed liposomal drug delivery system using micelle gradient as driving force to improve amphiphilic drug retention and its anti-tumor efficacy Abstract Abstract To improve drug retention in carriers for amphiphilic asulacrine (ASL), a novel active loading method using micelle gradient was developed to fabricate the...
PMC9071095
core_pubmed_pmc
Pharmacokinetic-Pharmacodynamic Model of Vedolizumab for Targeting Endoscopic Remission in Patients With Crohn Disease: Posthoc Analysis of the LOVE-CD Study
Pharmacokinetic-Pharmacodynamic Model of Vedolizumab for Targeting Endoscopic Remission in Patients With Crohn Disease: Posthoc Analysis of the LOVE-CD Study Abstract Abstract Background Higher serum concentrations of vedolizumab have been associated with improved outcomes in inflammatory bowel disease. It is unclear h...
PMC11111609
core_pubmed_pmc
Population Pharmacokinetics of the Anti-Interferon-Gamma Monoclonal Antibody Emapalumab: An Updated Analysis
Population Pharmacokinetics of the Anti-Interferon-Gamma Monoclonal Antibody Emapalumab: An Updated Analysis Abstract Introduction Emapalumab is a fully human monoclonal antibody that targets free and receptor-bound interferon-gamma (IFNγ), neutralizing its biological activity. IFNγ levels differ by orders of magnitude...
PMC11377050
core_pubmed_pmc
Comparison of intravenous versus perineural dexamethasone as a local anaesthetic adjunct for peripheral nerve blocks in the lower limb
Comparison of intravenous versus perineural dexamethasone as a local anaesthetic adjunct for peripheral nerve blocks in the lower limb Abstract BACKGROUND As a local anaesthetic adjunct, the systemic absorption of perineural dexamethasone in the lower limb could be restricted because of decreased vascularity when compa...
PMC12944594
core_pubmed_pmc
Development and Validation of a UPLC-MS/MS Method for the Quantification of Amantadine in Rat Plasma: Application to a Pharmacokinetic Study Under High-Altitude Hypoxia and Mechanistic Insights
Development and Validation of a UPLC-MS/MS Method for the Quantification of Amantadine in Rat Plasma: Application to a Pharmacokinetic Study Under High-Altitude Hypoxia and Mechanistic Insights Abstract Background/Objectives : This study aimed to develop an ultra-performance liquid chromatography–tandem mass spectromet...
PMC3558805
core_pubmed_pmc
First-in-man safety and pharmacokinetics of synthetic ozonide OZ439 demonstrates an improved exposure profile relative to other peroxide antimalarials
First-in-man safety and pharmacokinetics of synthetic ozonide OZ439 demonstrates an improved exposure profile relative to other peroxide antimalarials Abstract Aims To assess the safety and pharmacokinetics of a new synthetic ozonide antimalarial, OZ439, in a first-in-man, double-blind study in healthy volunteers. Meth...
PMC8326712
core_pubmed_pmc
Adaptive study design to assess effect of TRPV4 inhibition in patients with chronic cough
Adaptive study design to assess effect of TRPV4 inhibition in patients with chronic cough Abstract Abstract Objective Airway sensory nerves involved in the cough reflex are activated by adenosine triphosphate (ATP) agonism of P2X purinoceptor 3 (P2X3) receptors. Transient receptor potential vanilloid 4 (TRPV4) channel ...
PMC12283818
core_pubmed_pmc
Melatonin for prevention of delirium in patients receiving mechanical ventilation in the intensive care unit: a multiarm multistage adaptive randomized controlled clinical trial (DEMEL)
Melatonin for prevention of delirium in patients receiving mechanical ventilation in the intensive care unit: a multiarm multistage adaptive randomized controlled clinical trial (DEMEL) Abstract Abstract Purpose To determine the dose of melatonin with an optimal pharmacokinetic profile and to test whether this dose red...
PMC12462634
core_pubmed_pmc
DrugCombo: an informatics bridge for anticancer drug combination Phase I trial design
DrugCombo: an informatics bridge for anticancer drug combination Phase I trial design Abstract Abstract The promise of combinational drug therapies for cancer is hindered by the high failure rate of Phase I trials, perhaps attributable to the inavailability of an integrated source of toxicity data for cancer drugs to a...
PMC7533387
core_pubmed_pmc
Pharmacokinetics of thalidomide in dogs: can feeding affect it? A preliminary study
Pharmacokinetics of thalidomide in dogs: can feeding affect it? A preliminary study Abstract Abstract Background Tumor-associated neoangiogenesis is a crucial target for antitumor therapies. Thalidomide (TAL) is a promising anti-neoangiogenetic drug that has recently been used in the treatment of several malignancies i...
PMC10043195
core_pubmed_pmc
PBPK-based dose finding for sildenafil in pregnant women for antenatal treatment of congenital diaphragmatic hernia
PBPK-based dose finding for sildenafil in pregnant women for antenatal treatment of congenital diaphragmatic hernia Abstract Abstract Sildenafil is a potent vasodilator and phosphodiesterase type five inhibitor, commercially known as Revatio ® and approved for the treatment of pulmonary arterial hypertension. Maternal ...
PMC8149166
core_pubmed_pmc
An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19
An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19 Abstract Objectives We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir–interferon (IFN)-β-1a...
PMC10180080
core_pubmed_pmc
A Remarkable Difference in Pharmacokinetics of Fluorinated Versus Iodinated Photosensitizers Derived from Chlorophyll-a and a Direct Correlation between the Tumor Uptake and Anti-Cancer Activity
A Remarkable Difference in Pharmacokinetics of Fluorinated Versus Iodinated Photosensitizers Derived from Chlorophyll-a and a Direct Correlation between the Tumor Uptake and Anti-Cancer Activity Abstract To investigate and compare the pharmacokinetic profile and anti-cancer activity of fluorinated and iodinated photose...
PMC11983324
core_pubmed_pmc
Exploratory Study of Sex Differences in P‐Glycoprotein Function at the Blood–Brain Barrier
Exploratory Study of Sex Differences in P‐Glycoprotein Function at the Blood–Brain Barrier Abstract ABSTRACT Permeability‐glycoprotein (P‐gp), a crucial efflux pump transporter encoded by the ABCB1 gene, plays a pivotal role in drug disposition at the blood–brain barrier (BBB) and is involved in the pharmacokinetics of...
PMC6363067
core_pubmed_pmc
Open Source Pharmacokinetic/Pharmacodynamic Framework: Tutorial on the BioGears Engine
Open Source Pharmacokinetic/Pharmacodynamic Framework: Tutorial on the BioGears Engine Abstract Abstract BioGears is an open‐source, lumped parameter, full‐body human physiology engine. Its purpose is to provide realistic and comprehensive simulations for medical training, research, and education. BioGears incorporates...
PMC3035038
core_pubmed_pmc
A Novel Paclitaxel Microemulsion Containing a Reduced Amount of Cremophor EL: Pharmacokinetics, Biodistribution, and In Vivo Antitumor Efficacy and Safety
A Novel Paclitaxel Microemulsion Containing a Reduced Amount of Cremophor EL: Pharmacokinetics, Biodistribution, and In Vivo Antitumor Efficacy and Safety Abstract Abstract The purpose of this study was to prepare a novel paclitaxel (PTX) microemulsion containing a reduced amount of Cremophor EL (CrEL) which had simila...
PMC9083543
core_pubmed_pmc
Minimal Physiologically-Based Pharmacokinetic (mPBPK) Metamodeling of Target Engagement in Skin Informs Anti-IL17A Drug Development in Psoriasis
Minimal Physiologically-Based Pharmacokinetic (mPBPK) Metamodeling of Target Engagement in Skin Informs Anti-IL17A Drug Development in Psoriasis Abstract Abstract The pharmacologic effect(s) of biotherapeutics directed against soluble targets are driven by the magnitude and duration of free target suppression at the ti...
PMC4098115
core_pubmed_pmc
In Vivo Imaging of Multidrug Resistance Using a Third Generation MDR1 Inhibitor
In Vivo Imaging of Multidrug Resistance Using a Third Generation MDR1 Inhibitor Abstract Abstract Cellular up-regulation of multidrug resistance protein 1 (MDR1) is a common cause for resistance to chemotherapy; development of third generation MDR1 inhibitors—several of which contain a common 6,7-dimethoxy-2-phenethyl-...
PMC12051621
core_pubmed_pmc
A pharmacokinetic and safety study of oral arsenic trioxide in patients with acute promyelocytic leukemia
A pharmacokinetic and safety study of oral arsenic trioxide in patients with acute promyelocytic leukemia Abstract Key Points • In this crossover PK study, SY-2101 in the fasted state demonstrated comparable systemic exposure to ATO IV. • The similar PK between SY-2101 and ATO IV supports the likelihood of clinical equ...
PMC6395911
core_pubmed_pmc
Bone and Joint Tissue Penetration of the Staphylococcus -Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery
Bone and Joint Tissue Penetration of the Staphylococcus -Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery Abstract Afabicin (formerly Debio 1450, AFN-1720) is a prodrug of afabicin desphosphono (Debio 1452, AFN-1252), a novel antibiotic in development which targets the staphylococca...
PMC9311539
core_pubmed_pmc
Antibacterial Activity against Clinical Isolates and In Vivo Efficacy of Coralmycins
Antibacterial Activity against Clinical Isolates and In Vivo Efficacy of Coralmycins Abstract Abstract Coralmycins, such as coralmycin A and DH-coralmycin A, have novel molecular skeletons and have been reported to exhibit potent antibacterial activity against standard Gram-positive bacterial strains. Here, the in vitr...
PMC10045098
core_pubmed_pmc
Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration
Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration Abstract Nanoparticle (NP) pharmacokinetics significantly differ from traditional small molecule principles. From this emerges the need to create new tools and concepts to harness their full pot...
PMC4271452
core_pubmed_pmc
Determining the mechanisms underlying augmented renal drug clearance in the critically ill: use of exogenous marker compounds
Determining the mechanisms underlying augmented renal drug clearance in the critically ill: use of exogenous marker compounds Abstract Introduction The aim of this study was to explore changes in glomerular filtration (GFR) and renal tubular function in critically ill patients at risk of augmented renal clearance (ARC)...
PMC5750663
core_pubmed_pmc
Application of Pharmacokinetics Modelling to Predict Human Exposure of a Cationic Liposomal Subunit Antigen Vaccine System
Application of Pharmacokinetics Modelling to Predict Human Exposure of a Cationic Liposomal Subunit Antigen Vaccine System Abstract Abstract The pharmacokinetics of a liposomal subunit antigen vaccine system composed of the cationic lipid dimethyldioctadecylammonium bromide (DDA) and the immunostimulatory agent trehalo...
PMC4992793
core_pubmed_pmc
Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins
Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins Abstract Biologics have emerged as a powerful and diverse class of molecular and cell-based therapies that are capable of replacing enzymes, editing genomes, targeting tumors, and more. As this complex array of tools aris...
PMC9372427
core_pubmed_pmc
Tutorial: Statistical analysis and reporting of clinical pharmacokinetic studies
Tutorial: Statistical analysis and reporting of clinical pharmacokinetic studies Abstract Abstract Pharmacokinetics is the cornerstone of understanding drug absorption, distribution, metabolism, and elimination. It is also the key to describing variability in drug response caused by drug‐drug interactions (DDIs), pharm...
PMC8694146
core_pubmed_pmc
Population Pharmacokinetics and Dosing Optimization of Piperacillin-Tazobactam in Critically Ill Patients on Extracorporeal Membrane Oxygenation and the Influence of Concomitant Renal Replacement Therapy
Population Pharmacokinetics and Dosing Optimization of Piperacillin-Tazobactam in Critically Ill Patients on Extracorporeal Membrane Oxygenation and the Influence of Concomitant Renal Replacement Therapy Abstract ABSTRACT Critical illness and extracorporeal circulation, such as extracorporeal membrane oxygenation (ECMO...
PMC7608663
core_pubmed_pmc
Pharmacokinetic–pharmacodynamic modelling of the hypoglycaemic effect of pulsatile administration of human insulin in rats
Pharmacokinetic–pharmacodynamic modelling of the hypoglycaemic effect of pulsatile administration of human insulin in rats Abstract The relationship between the plasma insulin (INS) concentration–time course and plasma glucose concentration–time course during and after pulsatile INS administration to rats was character...
PMC5055355
core_pubmed_pmc
Impact of Age and Sex on CD4+ Cell Count Trajectories following Treatment Initiation: An Analysis of the Tanzanian HIV Treatment Database
Impact of Age and Sex on CD4+ Cell Count Trajectories following Treatment Initiation: An Analysis of the Tanzanian HIV Treatment Database Abstract Objective New guidelines recommend that all HIV-infected individuals initiate antiretroviral treatment (ART) immediately following diagnosis. This study describes how immune...
PMC8809196
core_pubmed_pmc
Simultaneous pharmacokinetic/pharmacodynamic (PKPD) assessment of ampicillin and gentamicin in the treatment of neonatal sepsis
Simultaneous pharmacokinetic/pharmacodynamic (PKPD) assessment of ampicillin and gentamicin in the treatment of neonatal sepsis Abstract Abstract Objectives This study aimed to simultaneously investigate the pharmacokinetics of ampicillin and gentamicin, currently the WHO standard of care for treating neonatal sepsis. ...
PMC11382051
core_pubmed_pmc
Multi-omics reveals protective effects of Ling Gui Zhu Gan Decoction on hyperlipidaemia in hamster
Multi-omics reveals protective effects of Ling Gui Zhu Gan Decoction on hyperlipidaemia in hamster Abstract Abstract Ling Gui Zhu Gan decoction (LGZGD) is a traditional Chinese medicine (TCM) prescription that is widely used in cardiovascular disease clinical prevention and treatment with high efficacy. Recent studies ...
PMC10955330
core_pubmed_pmc
Synthesis of salcaprozate sodium and its significance in enhancing pancreatic kininogenase absorption performance
Synthesis of salcaprozate sodium and its significance in enhancing pancreatic kininogenase absorption performance Abstract Abstract We conducted pharmacokinetic research wherein salcaprozate sodium (SNAC) was utilized as a penetration enhancer by incorporating it into pancreatic kininogenase (PK) to improve the bioavai...
PMC5890687
core_pubmed_pmc
Visceral leishmaniasis relapse hazard is linked to reduced miltefosine exposure in patients from Eastern Africa: a population pharmacokinetic/pharmacodynamic study
Visceral leishmaniasis relapse hazard is linked to reduced miltefosine exposure in patients from Eastern Africa: a population pharmacokinetic/pharmacodynamic study Abstract Abstract Background Low efficacy of miltefosine in the treatment of visceral leishmaniasis was recently observed in Eastern Africa. Objectives To d...
PMC11674295
core_pubmed_pmc
Small Molecule with Big Impact: Metarrestin Targets the Perinucleolar Compartment in Cancer Metastasis
Small Molecule with Big Impact: Metarrestin Targets the Perinucleolar Compartment in Cancer Metastasis Abstract Metarrestin (ML246) is a first-in-class pyrrole–pyrimidine-derived small molecule that selectively targets the perinucleolar compartment (PNC). PNC is a distinct subnuclear structure predominantly found in so...
PMC6951481
core_pubmed_pmc
Pharmacokinetics and enterohepatic circulation of jervine, an antitumor steroidal alkaloid from Veratrum nigrum in rats
Pharmacokinetics and enterohepatic circulation of jervine, an antitumor steroidal alkaloid from Veratrum nigrum in rats Abstract Abstract Jervine, a novel steroidal alkaloid from Veratrum nigrum L., exhibits both antitumor effect and potential toxicity. The aim of study was to characterize the pharmacokinetic behaviors...
PMC11768147
core_pubmed_pmc
Partial AUCs in Long-Acting Injectables: Rationale, Challenges, Variability, Usefulness, and Clinical Relevance
Partial AUCs in Long-Acting Injectables: Rationale, Challenges, Variability, Usefulness, and Clinical Relevance Abstract Abstract Regulatory authorities typically require bioequivalence to be demonstrated by comparing pharmacokinetic parameters like area under the plasma concentration-time curve (AUC) and maximum plasm...
PMC12135060
core_pubmed_pmc
Development of a Physiologically Based Biopharmaceutics Model Report Template: Considerations for Improved Quality in View of Regulatory Submissions
Development of a Physiologically Based Biopharmaceutics Model Report Template: Considerations for Improved Quality in View of Regulatory Submissions Abstract Pharmaceutical innovators and generic companies use Physiologically Based Biopharmaceutics Models (PBBMs) to guide drug product development and potentially waive ...
PMC12649734
core_pubmed_pmc
Targeting Oral Pathogens with Salvia officinalis and Nigella sativa Supercritical CO 2 Extracts: A Pharmacodynamic Approach and Three-Dimensional Checkerboard Synergy for Novel Dental Antimicrobials
Targeting Oral Pathogens with Salvia officinalis and Nigella sativa Supercritical CO 2 Extracts: A Pharmacodynamic Approach and Three-Dimensional Checkerboard Synergy for Novel Dental Antimicrobials Abstract Abstract Background : Oral infections such as dental caries and candidiasis are mediated by resilient biofilms, ...
PMC9249724
core_pubmed_pmc
Population Pharmacokinetics and Dosing Simulations of Ceftriaxone in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (An ASAP ECMO Study)
Population Pharmacokinetics and Dosing Simulations of Ceftriaxone in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (An ASAP ECMO Study) Abstract Background Despite the surge in use of extracorporeal membrane oxygenation (ECMO) in the adult intensive care unit, little guidance is available on the...
PMC10045483
core_pubmed_pmc
Comparative Pharmacokinetic Study of 5 Active Ingredients after Oral Administration of Zuogui Pill in Osteoporotic Rats with Different Syndrome Types
Comparative Pharmacokinetic Study of 5 Active Ingredients after Oral Administration of Zuogui Pill in Osteoporotic Rats with Different Syndrome Types Abstract Zuogui Pill is a kidney-yin-tonifying formula in traditional Chinese medicine that is widely used to manage osteoporosis with kidney-yin-deficiency in China. Her...
PMC10635345
core_pubmed_pmc
Busulfan Interlaboratory Proficiency Testing Program Revealed Worldwide Errors in Drug Quantitation and Dose Recommendations
Busulfan Interlaboratory Proficiency Testing Program Revealed Worldwide Errors in Drug Quantitation and Dose Recommendations Abstract Background: The clinical outcomes of busulfan-based conditioning regimens for hematopoietic cell transplantation (HCT) have been improved by personalizing the doses to target narrow busu...
PMC7651685
core_pubmed_pmc
The rate of dasotraline brain entry is slow following intravenous administration
The rate of dasotraline brain entry is slow following intravenous administration Abstract Rationale Drugs that rapidly increase dopamine levels have an increased risk of abuse. Dasotraline (DAS) is a dopamine and norepinephrine reuptake inhibitor characterized by slow oral absorption with low potential for abuse. Howev...
PMC8817058
core_pubmed_pmc
In Vitro to In Vivo Extrapolation Linked to Physiologically Based Pharmacokinetic Models for Assessing the Brain Drug Disposition
In Vitro to In Vivo Extrapolation Linked to Physiologically Based Pharmacokinetic Models for Assessing the Brain Drug Disposition Abstract Drug development for the central nervous system (CNS) is a complex endeavour with low success rates, as the structural complexity of the brain and specifically the blood-brain barri...