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PMC8361934
core_pubmed_pmc
Impact of Dose Delays and Alternative Dosing Regimens on Pertuzumab Pharmacokinetics
Impact of Dose Delays and Alternative Dosing Regimens on Pertuzumab Pharmacokinetics Abstract Abstract PERJETA (pertuzumab), administered with Herceptin (trastuzumab), is used in the treatment of human epidermal growth factor receptor 2‐positive breast cancer. Pertuzumab is currently approved with an initial loading do...
PMC7914186
core_pubmed_pmc
A randomized phase 1 single-dose polysomnography study of ASP8062, a GABA B receptor positive allosteric modulator
A randomized phase 1 single-dose polysomnography study of ASP8062, a GABA B receptor positive allosteric modulator Abstract Rationale Previous research suggests that sleep polysomnography and EEG endpoints can be used to assess GABAergic activity; however, the impact of GABA B receptor positive allosteric modulators on...
PMC12454544
core_pubmed_pmc
An overview on pharmaceutical applications of phosphodiesterase enzyme 5 (PDE5) inhibitors
An overview on pharmaceutical applications of phosphodiesterase enzyme 5 (PDE5) inhibitors Abstract Phosphodiesterase enzyme 5 (PDE5) inhibitors have emerged as one of the leading molecules for the treatment of erectile dysfunction (ED). PDE5 inhibitors are categorized structurally into several classes. PDE5 inhibitors...
PMC12422600
core_pubmed_pmc
Therapeutic Drug Monitoring of Beta-Lactams in Cystic Fibrosis: Unattained Target in Standard Antibiotic Dosing
Therapeutic Drug Monitoring of Beta-Lactams in Cystic Fibrosis: Unattained Target in Standard Antibiotic Dosing Abstract Abstract: Acute exacerbations of cystic fibrosis (CF) diminish quality of life and, if inadequately treated, can be life-threatening. The pathophysiological alterations associated with CF result in m...
PMC9017304
core_pubmed_pmc
Rifampin Pharmacokinetics/Pharmacodynamics in the Hollow-Fiber Model of Mycobacterium kansasii Infection
Rifampin Pharmacokinetics/Pharmacodynamics in the Hollow-Fiber Model of Mycobacterium kansasii Infection Abstract ABSTRACT There is limited high-quality evidence to guide the optimal treatment of Mycobacterium kansasii pulmonary disease. We retrospectively collected clinical data from 33 patients with M. kansasii pulmo...
PMC3681893
core_pubmed_pmc
Pharmacokinetics Study of Recombinant Hirudin in the Plasma of Rats Using Chromogenic Substrate, ELISA, and Radioisotope Assays
Pharmacokinetics Study of Recombinant Hirudin in the Plasma of Rats Using Chromogenic Substrate, ELISA, and Radioisotope Assays Abstract Aim To compare the analytical methods used to study the pharmacokinetics of recombinant hirudin in the plasma of rats that had been injected with 125 I-recombinant hirudin. Methods 2....
PMC4732406
core_pubmed_pmc
Anti-inflammatory effects of intravenous methotrexate associated with lipid nanoemulsions on antigen-induced arthritis
Anti-inflammatory effects of intravenous methotrexate associated with lipid nanoemulsions on antigen-induced arthritis Abstract Abstract OBJECTIVE: To test the hypothesis that intravenous use of methotrexate associated with lipid nanoemulsions can achieve superior anti-inflammatory effects in the joints of rabbits with...
PMC7076871
core_pubmed_pmc
Pharmacokinetic incompatibility of the Huanglian-Gancao herb pair
Pharmacokinetic incompatibility of the Huanglian-Gancao herb pair Abstract Abstract Background Pharmacokinetic interaction is one of the most important indices for the evaluation of the compatibility of herbal medicines. Both Gancao ( Glycyrrhizae Radix et Rhizoma ) and Huanglian ( Coptidis Rhizoma ) are commonly used ...
PMC9118863
core_pubmed_pmc
Bioimaging guided pharmaceutical evaluations of nanomedicines for clinical translations
Bioimaging guided pharmaceutical evaluations of nanomedicines for clinical translations Abstract Nanomedicines (NMs) have emerged as an efficient approach for developing novel treatment strategies against a variety of diseases. Over the past few decades, NM formulations have received great attention, and a large number...
PMC4978708
core_pubmed_pmc
Assessment of Potential Herb-Drug Interactions among Nigerian Adults with Type-2 Diabetes
Assessment of Potential Herb-Drug Interactions among Nigerian Adults with Type-2 Diabetes Abstract Abstract It is becoming increasingly evident that patients with diabetes do not rely only on prescription drugs for their disease management. The use of herbal medicines is one of the self-management practices adopted by ...
PMC11052883
core_pubmed_pmc
Clinical Pharmacology of the Antibody–Drug Conjugate Enfortumab Vedotin in Advanced Urothelial Carcinoma and Other Malignant Solid Tumors
Clinical Pharmacology of the Antibody–Drug Conjugate Enfortumab Vedotin in Advanced Urothelial Carcinoma and Other Malignant Solid Tumors Abstract Enfortumab vedotin is an antibody–drug conjugate comprised of a human monoclonal antibody directed to Nectin-4 and monomethyl auristatin E (MMAE), a microtubule-disrupting a...
PMC4230716
core_pubmed_pmc
Using Bayesian-PBPK modeling for assessment of inter-individual variability and subgroup stratification
Using Bayesian-PBPK modeling for assessment of inter-individual variability and subgroup stratification Abstract Purpose Inter-individual variability in clinical endpoints and occurrence of potentially severe adverse effects represent an enormous challenge in drug development at all phases of (pre-)clinical research. T...
PMC3499177
core_pubmed_pmc
Tumor penetration and epidermal growth factor receptor saturation by panitumumab correlate with antitumor activity in a preclinical model of human cancer
Tumor penetration and epidermal growth factor receptor saturation by panitumumab correlate with antitumor activity in a preclinical model of human cancer Abstract Abstract Background Successful treatment of solid tumors relies on the ability of drugs to penetrate into the tumor tissue. Methods We examined the correlati...
PMC8874516
core_pubmed_pmc
Linkers: An Assurance for Controlled Delivery of Antibody-Drug Conjugate
Linkers: An Assurance for Controlled Delivery of Antibody-Drug Conjugate Abstract Abstract As one of the major therapeutic options for cancer treatment, chemotherapy has limited selectivity against cancer cells. Consequently, this therapeutic strategy offers a small therapeutic window with potentially high toxicity and...
PMC3632017
core_pubmed_pmc
Cytochrome P450 3A4*1B as Pharmacogenomic Predictor of Tacrolimus Pharmacokinetics and Clinical Outcome in the Liver Transplant Recipients
Cytochrome P450 3A4*1B as Pharmacogenomic Predictor of Tacrolimus Pharmacokinetics and Clinical Outcome in the Liver Transplant Recipients Abstract Abstract Background and Aims: Tacrolimus is a macrolide immunosuppressant used for prevention of allograft rejection in organ transplantation and metabolized in the liver a...
PMC3976951
core_pubmed_pmc
Updates on the Clinical Evidenced Herb-Warfarin Interactions
Updates on the Clinical Evidenced Herb-Warfarin Interactions Abstract Abstract Increasing and inadvertent use of herbs makes herb-drug interactions a focus of research. Concomitant use of warfarin, a highly efficacious oral anticoagulant, and herbs causes major safety concerns due to the narrow therapeutic window of wa...
PMC11370030
core_pubmed_pmc
Appropriate use of triazolam in elderly patients considering a quantitative benefit-risk assessment based on the pharmacokinetic-pharmacodynamic modeling and simulation approach supported by real-world data
Appropriate use of triazolam in elderly patients considering a quantitative benefit-risk assessment based on the pharmacokinetic-pharmacodynamic modeling and simulation approach supported by real-world data Abstract Background Triazolam is a typical drug commonly used in the elderly; however, there have been concerns a...
PMC10499426
core_pubmed_pmc
Longitudinal estimated glomerular filtration rate ( eGFR) modeling in long‐term renal function to inform clinical trial design in kidney transplantation
Longitudinal estimated glomerular filtration rate ( eGFR) modeling in long‐term renal function to inform clinical trial design in kidney transplantation Abstract Abstract Kidney transplantation is the preferred treatment for individuals with end‐stage kidney disease. From a modeling perspective, our understanding of ki...
PMC10296897
core_pubmed_pmc
Drug-Eluting Embolic Loaded with Tyrosine Kinase Inhibitor Targeted Therapies for Transarterial Chemoembolization in a VX2 Model
Drug-Eluting Embolic Loaded with Tyrosine Kinase Inhibitor Targeted Therapies for Transarterial Chemoembolization in a VX2 Model Abstract Abstract Simple Summary Embolization shuts down vessels and cuts off the supply of blood to liver tumors. Using small beads, drugs can be delivered locally. Thus far, the drugs loade...
PMC7391402
core_pubmed_pmc
Integrated Item Response Theory Modeling of Multiple Patient-Reported Outcomes Assessing Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia
Integrated Item Response Theory Modeling of Multiple Patient-Reported Outcomes Assessing Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia Abstract In clinical trials within lower urinary tract symptoms due to benign prostatic hyperplasia (BPH-LUTS), the International Prostate Symptom Score (IPS...
PMC2965864
core_pubmed_pmc
A phase I, dose-finding study of sunitinib in combination with irinotecan in patients with advanced solid tumours
A phase I, dose-finding study of sunitinib in combination with irinotecan in patients with advanced solid tumours Abstract Background: Sunitinib is a multitargeted, oral tyrosine kinase inhibitor with antitumour and antiangiogenic activity. We investigated the safety and pharmacokinetics of sunitinib in combination wit...
PMC12731643
core_pubmed_pmc
Next-Generation HDAC Inhibitors: Advancing Zinc-Binding Group Design for Enhanced Cancer Therapy
Next-Generation HDAC Inhibitors: Advancing Zinc-Binding Group Design for Enhanced Cancer Therapy Abstract Highlights What are the main findings? This review systematically analyzes recently developed HDAC inhibitors in recent years, emphasizing structural evolution across CAP, linker, and zinc-binding groups (ZBGs). It...
PMC3722116
core_pubmed_pmc
Nonlinear Mixed-Effects Modelling of In Vitro Drug Susceptibility and Molecular Correlates of Multidrug Resistant Plasmodium falciparum
Nonlinear Mixed-Effects Modelling of In Vitro Drug Susceptibility and Molecular Correlates of Multidrug Resistant Plasmodium falciparum Abstract Abstract The analysis of in vitro anti-malarial drug susceptibility testing is vulnerable to the effects of different statistical approaches and selection biases. These confou...
PMC4187895
core_pubmed_pmc
A First-in-Human Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Oral Dose Study of Novel Antimalarial Spiroindolone KAE609 (Cipargamin) To Assess Its Safety, Tolerability, and Pharmacokinetics in Healthy Adult Volunteers
A First-in-Human Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Oral Dose Study of Novel Antimalarial Spiroindolone KAE609 (Cipargamin) To Assess Its Safety, Tolerability, and Pharmacokinetics in Healthy Adult Volunteers Abstract Abstract This first-in-human randomized, double-blind, place...
PMC8740159
core_pubmed_pmc
An LC-MS/MS method for simultaneous analysis of the cystic fibrosis therapeutic drugs colistin, ivacaftor and ciprofloxacin
An LC-MS/MS method for simultaneous analysis of the cystic fibrosis therapeutic drugs colistin, ivacaftor and ciprofloxacin Abstract Abstract Inhaled antibiotics such as colistin and ciprofloxacin are increasingly used to treat bacterial lung infections in cystic fibrosis patients. In this study, we established and val...
PMC9935793
core_pubmed_pmc
Liposomal Irinotecan Shows a Larger Therapeutic Index than Non-liposomal Irinotecan in Patient-Derived Xenograft Models of Pancreatic Cancer
Liposomal Irinotecan Shows a Larger Therapeutic Index than Non-liposomal Irinotecan in Patient-Derived Xenograft Models of Pancreatic Cancer Abstract Introduction Liposomal irinotecan promotes controlled sustained release of irinotecan (CPT-11), therefore, we hypothesize that the therapeutic index (quantitative measure...
PMC4405076
core_pubmed_pmc
Proposal for defining the relevance of drug accumulation derived from single dose study data for modified release dosage forms
Proposal for defining the relevance of drug accumulation derived from single dose study data for modified release dosage forms Abstract Abstract Recently, the European Medicines Agency (EMA) published the new draft guideline on the pharmacokinetic and clinical evaluation of modified release (MR) formulations. The draft...
PMC10610386
core_pubmed_pmc
The Amorphous Solid Dispersion of Chrysin in Plasdone ® S630 Demonstrates Improved Oral Bioavailability and Antihyperlipidemic Performance in Rats
The Amorphous Solid Dispersion of Chrysin in Plasdone ® S630 Demonstrates Improved Oral Bioavailability and Antihyperlipidemic Performance in Rats Abstract Chrysin is a flavonoid with various biological activities. However, its low water solubility and strong metabolism render its oral bioavailability rather poor. This...
PMC7539971
core_pubmed_pmc
Four phase 1 trials to evaluate the safety and pharmacokinetic profile of single and repeated dosing of SCO‐101 in adult male and female volunteers
Four phase 1 trials to evaluate the safety and pharmacokinetic profile of single and repeated dosing of SCO‐101 in adult male and female volunteers Abstract Abstract SCO‐101 (Endovion) was discontinued 20 years ago as a new drug under development against sickle cell anaemia. Data from the phase 1 studies remained unpub...
PMC11652485
core_pubmed_pmc
Determination of pharmacokinetic-pharmacodynamic cutoff values of oxytetracycline in calves and adult cattle using population pharmacokinetic modeling
Determination of pharmacokinetic-pharmacodynamic cutoff values of oxytetracycline in calves and adult cattle using population pharmacokinetic modeling Abstract Abstract Introduction A harmonized clinical breakpoint for interpreting antimicrobial susceptibility testing of oxytetracycline in cattle is currently lacking i...
PMC6765698
core_pubmed_pmc
Recommendations for the Design of Clinical Drug–Drug Interaction Studies With Itraconazole Using a Mechanistic Physiologically‐Based Pharmacokinetic Model
Recommendations for the Design of Clinical Drug–Drug Interaction Studies With Itraconazole Using a Mechanistic Physiologically‐Based Pharmacokinetic Model Abstract Regulatory agencies currently recommend itraconazole ( ITZ ) as a strong cytochrome P450 3A ( CYP 3A) inhibitor for clinical drug–drug interaction ( DDI ) s...
PMC5729885
core_pubmed_pmc
Comparative pharmacokinetics of a fixed-dose combination vs concomitant administration of telmisartan and S-amlodipine in healthy adult volunteers
Comparative pharmacokinetics of a fixed-dose combination vs concomitant administration of telmisartan and S-amlodipine in healthy adult volunteers Abstract Abstract Objective This study compared the pharmacokinetic (PK) and safety profiles of a fixed-dose combination (FDC) formulation of telmisartan and S-amlodipine wi...
PMC5644106
core_pubmed_pmc
KH176 under development for rare mitochondrial disease: a first in man randomized controlled clinical trial in healthy male volunteers
KH176 under development for rare mitochondrial disease: a first in man randomized controlled clinical trial in healthy male volunteers Abstract Abstract Background Mitochondrial disorders are a clinically, biochemically and genetically heterogeneous group of multi-system diseases, with an unmet medical need for treatme...
PMC6895963
core_pubmed_pmc
Is there an Exposure–Response Relationship for Nivolumab in Real-World NSCLC Patients?
Is there an Exposure–Response Relationship for Nivolumab in Real-World NSCLC Patients? Abstract Pharmacokinetic/pharmacodynamic data from real-world cohort are sparse in non small–cell lung cancer (NSCLC) patients treated with nivolumab. The aim of this prospective observational study was to explore the exposure-respon...
PMC9931032
core_pubmed_pmc
Elbasvir/grazoprevir in children aged 3–18 years with chronic HCV genotype 1 or 4 infection: a pharmacokinetic modeling study
Elbasvir/grazoprevir in children aged 3–18 years with chronic HCV genotype 1 or 4 infection: a pharmacokinetic modeling study Abstract Background: Approximately 3.5 million children and adolescents worldwide are chronically infected with HCV. This study uses pharmacokinetic modeling to identify pediatric doses of elbas...
PMC6639923
core_pubmed_pmc
Describing vancomycin serum levels in pediatric intensive care unit (ICU) patients: are expected goals being met
Describing vancomycin serum levels in pediatric intensive care unit (ICU) patients: are expected goals being met Abstract Abstract Background In the pediatric population, infections by methicillin-resistant Staphylococcus aureus (MRSA) are associated with significant morbidity and hospital costs. Vancomycin is a glycop...
PMC9246989
core_pubmed_pmc
Pharmacoproteomics of Brain Barrier Transporters and Substrate Design for the Brain Targeted Drug Delivery
Pharmacoproteomics of Brain Barrier Transporters and Substrate Design for the Brain Targeted Drug Delivery Abstract Abstract One of the major reasons why central nervous system (CNS)-drug development has been challenging in the past, is the barriers that prevent substances entering from the blood circulation into the b...
PMC6852000
core_pubmed_pmc
Pharmacokinetic/Pharmacodynamic Modeling to Support the Re‐approval of Gemtuzumab Ozogamicin
Pharmacokinetic/Pharmacodynamic Modeling to Support the Re‐approval of Gemtuzumab Ozogamicin Abstract Abstract Gemtuzumab ozogamicin (Mylotarg; Pfizer, New York, NY) was the first antibody–drug conjugate to be approved for CD33‐positive acute myeloid leukemia (AML). However, it was voluntarily withdrawn from the US mar...
PMC11201108
core_pubmed_pmc
GC-MS method for simultaneous determination and pharmacokinetic investigation of five volatile components in rat plasma after oral administration of the essential oil extract of Pogostemon cablin
GC-MS method for simultaneous determination and pharmacokinetic investigation of five volatile components in rat plasma after oral administration of the essential oil extract of Pogostemon cablin Abstract Pogostemon cablin (PC) is a traditional Chinese medicine (TCM) and food as well as an important essential oil plant...
PMC5861220
core_pubmed_pmc
The Cytochrome P450-Mediated Metabolism Alternation of Four Effective Lignans From Schisandra chinensis in Carbon Tetrachloride-Intoxicated Rats and Patients With Advanced Hepatocellular Carcinoma
The Cytochrome P450-Mediated Metabolism Alternation of Four Effective Lignans From Schisandra chinensis in Carbon Tetrachloride-Intoxicated Rats and Patients With Advanced Hepatocellular Carcinoma Abstract Abstract It is highly valuable to study the pharmacokinetics of herbal components under the pathological condition...
PMC4363646
core_pubmed_pmc
Pharmacogenomics and Herb-Drug Interactions: Merge of Future and Tradition
Pharmacogenomics and Herb-Drug Interactions: Merge of Future and Tradition Abstract The worldwide using of herb products and the increasing potential herb-drug interaction issue has raised enthusiasm on discovering the underlying mechanisms. Previous review indicated that the interactions may be mediated by metabolism ...
PMC7486547
core_pubmed_pmc
Enhancement of oral bioavailability and anti-Parkinsonian efficacy of resveratrol through a nanocrystal formulation
Enhancement of oral bioavailability and anti-Parkinsonian efficacy of resveratrol through a nanocrystal formulation Abstract Resveratrol (RES), a non-flavonoid polyphenol extracted from a wide variety of plants, exhibits neuroprotective activities against Parkinson's disease (PD). However, undesirable water solubility ...
PMC9443636
core_pubmed_pmc
Right dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock—a two-centre randomised clinical trial
Right dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock—a two-centre randomised clinical trial Abstract Background Adequate antibiotic dosing may improve outcomes in critically ill patients but is challenging due to altered and va...
PMC9543782
core_pubmed_pmc
Enantiospecific pharmacokinetics of intravenous dexmedetomidine in beagles
Enantiospecific pharmacokinetics of intravenous dexmedetomidine in beagles Abstract Abstract The goal of this study was to investigate the pharmacokinetic (PK) behaviour of dexmedetomidine in dogs administered as a pure enantiomer versus as part of a racemic mixture. Eight unmedicated intact purpose‐bread beagles were ...
PMC5912267
core_pubmed_pmc
Development and 10-year history of a biosimilar: the example of Binocrit ®
Development and 10-year history of a biosimilar: the example of Binocrit ® Abstract Patent expirations for several biological products have prompted the development of alternative versions, termed ‘biosimilars’, which have comparable quality, safety and efficacy to a licensed biological medicine (also referred to as th...
PMC11726161
core_pubmed_pmc
Phenol (bio)isosteres in drug design and development
Phenol (bio)isosteres in drug design and development Abstract Abstract Due to their versatile properties, phenolic compounds are integral to various biologically active molecules, including many pharmaceuticals. However, their application in drug design is often hindered by issues such as poor oral bioavailability, rap...
PMC9971153
core_pubmed_pmc
Efficacy and Safety of Denosumab Biosimilar QL1206 Versus Denosumab in Patients with Bone Metastases from Solid Tumors: A Randomized Phase III Trial
Efficacy and Safety of Denosumab Biosimilar QL1206 Versus Denosumab in Patients with Bone Metastases from Solid Tumors: A Randomized Phase III Trial Abstract Background Denosumab has been approved for the treatment of bone metastases from solid tumors. QL1206 is the first denosumab biosimilar and needs to be compared w...
PMC6691630
core_pubmed_pmc
Time course of psychomotor recovery after intravenous dexmedetomidine infusion as a part of balanced anaesthetic technique: A randomised, double-blind study
Time course of psychomotor recovery after intravenous dexmedetomidine infusion as a part of balanced anaesthetic technique: A randomised, double-blind study Abstract Background and Aims: Dexmedetomidine is a drug that is being widely used as an adjuvant to anaesthesia because of its unique pharmacodynamic and pharmacok...
PMC11855543
core_pubmed_pmc
The Combined Effects of Urine Zinc, Cadmium, Mercury, Lead, and Copper on Endometrial Cancer Staging
The Combined Effects of Urine Zinc, Cadmium, Mercury, Lead, and Copper on Endometrial Cancer Staging Abstract Endometrial cancer (EC) is a growing public health concern. This secondary data study of a case series leveraged existing samples and data to explore the potential link between exposure to heavy metals/essentia...
PMC10347152
core_pubmed_pmc
Chitosan-Based Nano Systems for Natural Antioxidants in Breast Cancer Therapy
Chitosan-Based Nano Systems for Natural Antioxidants in Breast Cancer Therapy Abstract Breast cancer is a major cause of death globally, accounting for around 13% of all deaths. Chemotherapy, the common treatment for cancer, can have side effects that lead to the production of reactive oxygen species (ROS) and an incre...
PMC10382374
core_pubmed_pmc
An individualized digital twin of a patient for transdermal fentanyl therapy for chronic pain management
An individualized digital twin of a patient for transdermal fentanyl therapy for chronic pain management Abstract Fentanyl transdermal therapy is a suitable treatment for moderate-to-severe cancer-related pain. The inter-individual variability of the patients leads to different therapy responses. This study aims to det...
PMC9134108
core_pubmed_pmc
Antimicrobial Dosing Recommendations in Pediatric Continuous Renal Replacement Therapy: A Critical Appraisal of Current Evidence
Antimicrobial Dosing Recommendations in Pediatric Continuous Renal Replacement Therapy: A Critical Appraisal of Current Evidence Abstract Abstract Objectives Continuous renal replacement therapy (CRRT) is commonly employed in critically ill children and is known to affect antimicrobial pharmacokinetics. There is a lack...
PMC5225197
core_pubmed_pmc
LJM716 in Japanese patients with head and neck squamous cell carcinoma or HER2-overexpressing breast or gastric cancer
LJM716 in Japanese patients with head and neck squamous cell carcinoma or HER2-overexpressing breast or gastric cancer Abstract Abstract Purpose Human epidermal growth factor receptor 3 (HER3) has been identified as an important component of many receptor tyrosine kinase-driven cancers. LJM716 is a human IgG monoclonal...
PMC8097454
core_pubmed_pmc
Pharmacokinetic Study of Rectal Artesunate in Children with Severe Malaria in Africa
Pharmacokinetic Study of Rectal Artesunate in Children with Severe Malaria in Africa Abstract When severe malaria is suspected in children, the WHO recommends pretreatment with a single rectal dose of artesunate before referral to an appropriate facility. This was an individually randomized, open-label, 2-arm, crossove...
PMC12961469
core_pubmed_pmc
Beyond MIDAS: An In Silico Study of a Putative Noncanonical C16 Binding Site in αvβ3 Integrin
Beyond MIDAS: An In Silico Study of a Putative Noncanonical C16 Binding Site in αvβ3 Integrin Abstract Abstract Integrins are essential transmembrane receptors that mediate bidirectional signaling between the extracellular matrix (ECM) and the cytoskeleton. Among them, αvβ3 and α5β1 are key regulators of angiogenesis, ...
PMC5364972
core_pubmed_pmc
Construction and verification of CYP3A5 gene polymorphisms using a Saccharomyces cerevisiae expression system to predict drug metabolism
Construction and verification of CYP3A5 gene polymorphisms using a Saccharomyces cerevisiae expression system to predict drug metabolism Abstract Abstract The present study evaluated the ability of a Saccharomyces cerevisiae expression system to predict the pharmacokinetic (PK) activity of a calcium channel blocker in ...
PMC4277828
core_pubmed_pmc
Randomized pharmacokinetic evaluation of different rifabutin doses in African HIV- infected tuberculosis patients on lopinavir/ritonavir-based antiretroviral therapy
Randomized pharmacokinetic evaluation of different rifabutin doses in African HIV- infected tuberculosis patients on lopinavir/ritonavir-based antiretroviral therapy Abstract Background Pharmacokinetic interactions between rifampicin and protease inhibitors (PIs) complicate the management of HIV-associated tuberculosis...
PMC11284553
core_pubmed_pmc
Potentiation of the muscarinic acetylcholine receptor 1 modulates neurophysiological features in a mouse model of Rett syndrome
Potentiation of the muscarinic acetylcholine receptor 1 modulates neurophysiological features in a mouse model of Rett syndrome Abstract Rett syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in the X chromosome-linked gene Methyl-CpG Binding Protein 2 ( MECP2 ). Restoring MeCP2 expression a...
PMC5012851
core_pubmed_pmc
A preliminary evaluation of the relationship of cannabinoid blood concentrations with the analgesic response to vaporized cannabis
A preliminary evaluation of the relationship of cannabinoid blood concentrations with the analgesic response to vaporized cannabis Abstract Abstract A randomized, placebo-controlled crossover trial utilizing vaporized cannabis containing placebo and 6.7% and 2.9% delta-9-tetrahydrocannabinol (THC) was performed in 42 s...
PMC10333676
core_pubmed_pmc
Development of KEAP1-targeting PROTAC and its antioxidant properties: In vitro and in vivo
Development of KEAP1-targeting PROTAC and its antioxidant properties: In vitro and in vivo Abstract Oxidative stress due to abnormal accumulation of reactive oxygen species (ROS) is an initiator of a large number of human diseases, and thus, the elimination and prevention of excessive ROS are important aspects of preve...
PMC10176804
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EnGraft: a multicentre, open-label, randomised, two-arm, superiority study protocol to assess bioavailability and practicability of Envarsus® versus Advagraf™ in liver transplant recipients
EnGraft: a multicentre, open-label, randomised, two-arm, superiority study protocol to assess bioavailability and practicability of Envarsus® versus Advagraf™ in liver transplant recipients Abstract Abstract Background Graft rejection and chronic CNI toxicity remain obstacles to organ transplant success. Current formul...
PMC8224699
core_pubmed_pmc
Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis
Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis Abstract Cancer causes a considerable amount of mortality in the world, while arthritis is an immunological dysregulation with multifactorial pathogenesis including genetic and environmental defect...
PMC7317019
core_pubmed_pmc
Gene Polymorphisms Affecting the Pharmacokinetics and Pharmacodynamics of Donepezil Efficacy
Gene Polymorphisms Affecting the Pharmacokinetics and Pharmacodynamics of Donepezil Efficacy Abstract Donepezil (DNP) is the first-line drug used for Alzheimer's disease (AD). However, the therapeutic response rate of patients to DNP varies from 20 to 60%. The main reason for the large differences in the clinical effic...
PMC7920489
core_pubmed_pmc
Design and Mechanism of Action of a New Prototype of Combi-Molecule “Programed” to Release Bioactive Species at a pH Range Akin to That of the Tumor Microenvironment
Design and Mechanism of Action of a New Prototype of Combi-Molecule “Programed” to Release Bioactive Species at a pH Range Akin to That of the Tumor Microenvironment Abstract Abstract The clinical use of cytotoxic agents is plagued by systemic toxicity. We report a novel approach that seeks to design a “combi-molecule”...
PMC7211345
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Protection of renal damage by HMG-CoA inhibitors: A comparative study between atorvastatin and rosuvastatin
Protection of renal damage by HMG-CoA inhibitors: A comparative study between atorvastatin and rosuvastatin Abstract Objective(s): Hypercholesterolemia is a common metabolic disorder in developing and developed countries and is associated with the increased rates of chronic kidney disease (CKD). Statin therapy could re...
PMC12567096
core_pubmed_pmc
An Efficacy- and In Vivo Exposure-Oriented Integrated Study to Investigate the Effective Components of Qishen Granule
An Efficacy- and In Vivo Exposure-Oriented Integrated Study to Investigate the Effective Components of Qishen Granule Abstract Background : Qishen granule (QSG) is a widely prescribed herbal formula for the treatment of chronic heart failure. The mechanisms of action of QSG have been clarified; however, the effective s...
PMC6071856
core_pubmed_pmc
Optimizing Clinical Trial Design to Maximize Evidence Generation in Pediatric HIV
Optimizing Clinical Trial Design to Maximize Evidence Generation in Pediatric HIV Abstract Abstract: For HIV-infected children, formulation development, pharmacokinetic (PK) data, and evaluation of early toxicity are critical for licensing new antiretroviral drugs; direct evidence of efficacy in children may not be nee...
PMC5900965
core_pubmed_pmc
In Vitro and In Vivo Investigation of Potential for Complex CYP3A Interaction for PF‐00251802 (Dagrocorat), a Novel Dissociated Agonist of the Glucocorticoid Receptor
In Vitro and In Vivo Investigation of Potential for Complex CYP3A Interaction for PF‐00251802 (Dagrocorat), a Novel Dissociated Agonist of the Glucocorticoid Receptor Abstract Abstract The dissociated agonists of the glucocorticoid receptor are a novel class of agents in clinical development for rheumatoid arthritis. P...
PMC6003283
core_pubmed_pmc
Pharmacokinetic evaluation of D-ribose after oral and intravenous administration to healthy rabbits
Pharmacokinetic evaluation of D-ribose after oral and intravenous administration to healthy rabbits Abstract Abstract Introduction This study explored D-ribose pharmacokinetics after intravenous (IV) and oral administration to healthy rabbits. Materials and methods D-ribose was administered once as 420 mg/kg (N=4) or 8...
PMC9639143
core_pubmed_pmc
Pharmacokinetics of hydroxychloroquine in paediatric lupus: data from a novel, direct-to-family clinical trial
Pharmacokinetics of hydroxychloroquine in paediatric lupus: data from a novel, direct-to-family clinical trial Abstract Abstract Objective Determine the pharmacokinetics (PK) and exposure–response of hydroxychloroquine (HCQ) and desethylhydroxychloroquine (DHCQ) in paediatric SLE (pSLE). Methods We conducted an explora...
PMC7753357
core_pubmed_pmc
Population Pharmacokinetics and Model-Based Dosing Optimization of Teicoplanin in Pediatric Patients
Population Pharmacokinetics and Model-Based Dosing Optimization of Teicoplanin in Pediatric Patients Abstract Objectives: The pharmacokinetics (PK) of teicoplanin differs in children compared with adults. Our aim was to determine the PK of teicoplanin in an Asian pediatric population and to optimize dosage regimens. Me...
PMC8971378
core_pubmed_pmc
Identification, analysis of deleterious SNPs of the human GSR gene and their effects on the structure and functions of associated proteins and other diseases
Identification, analysis of deleterious SNPs of the human GSR gene and their effects on the structure and functions of associated proteins and other diseases Abstract Abstract Hereditary glutathione reductase deficiency, caused by mutations of the GSR gene, is an autosomal recessive disorder characterized by decreased ...
PMC5916460
core_pubmed_pmc
Pharmacokinetics, Safety and Efficacy of Maraviroc in Treatment-experienced Pediatric Patients Infected With CCR5-Tropic HIV-1
Pharmacokinetics, Safety and Efficacy of Maraviroc in Treatment-experienced Pediatric Patients Infected With CCR5-Tropic HIV-1 Abstract Supplemental Digital Content is available in the text. Background: Maraviroc is a CC-chemokine receptor 5 antagonist approved to treat adults infected with CC-chemokine receptor 5–trop...
PMC7359142
core_pubmed_pmc
10th Anniversary of a Two-Stage Design in Bioequivalence. Why Has it Still Not Been Implemented?
10th Anniversary of a Two-Stage Design in Bioequivalence. Why Has it Still Not Been Implemented? Abstract Abstract Purpose In 2010 the European Medicines Agency allowed a two-stage design in bioequivalence studies. However, in the public domain there are mainly articles describing the theoretical and statistical base f...
PMC10819769
core_pubmed_pmc
Quetiapine-Related Deaths: In Search of a Surrogate Endpoint
Quetiapine-Related Deaths: In Search of a Surrogate Endpoint Abstract Abstract Quetiapine is a second-generation antipsychotic drug available for two and half decades. Due to increased misuse, prescription outside the approved indications, and availability on the black market, it is being encountered in medicolegal aut...
PMC8945294
core_pubmed_pmc
Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma
Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma Abstract Key Points Glofitamab induced dose-dependent induction of cytokines and T-cell margination, proliferation, and activation in peripheral blood. Tumor cell intrinsic factors (eg, TP53 and MYC signaling...
PMC12871332
core_pubmed_pmc
75 Years of Mathematical Oncology
75 Years of Mathematical Oncology Abstract Abstract Mathematics has long provided a quantitative framework to interpret cancer biology and treatment. Driven by richer biological and clinical data, the field has evolved into a multidisciplinary and translational endeavor - giving rise to Mathematical Oncology. Yet, the ...
PMC11616473
core_pubmed_pmc
Combating PDAC Drug Resistance: The Role of Ref-1 Inhibitors in Accelerating Progress in Pancreatic Cancer Research
Combating PDAC Drug Resistance: The Role of Ref-1 Inhibitors in Accelerating Progress in Pancreatic Cancer Research Abstract Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most lethal solid tumor diagnoses given its limited treatment options and dismal prognosis. Its complex tumor microenvironment (TME), he...
PMC3159682
core_pubmed_pmc
Pharmacokinetics of pirfenidone after topical administration in rabbit eye
Pharmacokinetics of pirfenidone after topical administration in rabbit eye Abstract Purpose Pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) is a new, broad-spectrum agent that has an inhibition effect on the proliferation, migration, and collagen contraction of human Tenon’s fibroblasts, and thus modulating the wound h...
PMC4263185
core_pubmed_pmc
Contrasting benefits of different artemisinin combination therapies as first-line malaria treatments using model-based cost-effectiveness analysis
Contrasting benefits of different artemisinin combination therapies as first-line malaria treatments using model-based cost-effectiveness analysis Abstract There are currently several recommended drug regimens for uncomplicated falciparum malaria in Africa. Each has different properties that determine its impact on dis...
PMC11871688
core_pubmed_pmc
A perspective review on the systematic implementation of ctDNA in phase I clinical trial drug development
A perspective review on the systematic implementation of ctDNA in phase I clinical trial drug development Abstract Abstract Circulating tumour DNA (ctDNA) represents an increasingly important biomarker for the screening, diagnosis and management of patients in clinical practice in advanced/metastatic disease across mul...
PMC10277867
core_pubmed_pmc
Mechanistic evaluation of the inhibitory effect of four SGLT-2 inhibitors on SGLT 1 and SGLT 2 using physiologically based pharmacokinetic (PBPK) modeling approaches
Mechanistic evaluation of the inhibitory effect of four SGLT-2 inhibitors on SGLT 1 and SGLT 2 using physiologically based pharmacokinetic (PBPK) modeling approaches Abstract Abstract Sodium-glucose co-transporter type 2 (SGLT 2, gliflozins) inhibitors are potent orally active drugs approved for managing type 2 diabete...
PMC6005026
core_pubmed_pmc
Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation
Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation Abstract Abstract Objectives The oxazolidinone linezolid is an effective component of drug-resistant TB treatment, but its use is limited by toxicity and the optimum dose is uncertain. Current strategies are not informed...
PMC10741200
core_pubmed_pmc
Pharmacodynamics of Doripenem Alone and in Combination with Relebactam in an In Vitro Hollow-Fiber Dynamic Model: Emergence of Resistance of Carbapenemase-Producing Klebsiella pneumoniae and the Inoculum Effect
Pharmacodynamics of Doripenem Alone and in Combination with Relebactam in an In Vitro Hollow-Fiber Dynamic Model: Emergence of Resistance of Carbapenemase-Producing Klebsiella pneumoniae and the Inoculum Effect Abstract The emergence of bacteria resistant to beta-lactam/beta-lactamase inhibitor combinations is insuffic...
PMC10582055
core_pubmed_pmc
Herb-drug interaction: Effect of sinapic acid on the pharmacokinetics of dasatinib in rats
Herb-drug interaction: Effect of sinapic acid on the pharmacokinetics of dasatinib in rats Abstract Abstract Dasatinib (DAS) is a narrow therapeutic index drug and novel oral multitarget inhibitor of tyrosine kinase and approved for the first-line therapy for chronic myelogenous leukemia (CML) and Philadelphia chromoso...
PMC7691403
core_pubmed_pmc
Comparability Considerations and Challenges for Expedited Development Programs for Biological Products
Comparability Considerations and Challenges for Expedited Development Programs for Biological Products Abstract Expedited development programs for biological products to be used in the treatment of serious conditions bring about challenges because of the compressed clinical development timeframes. As expedited developm...
PMC10309098
core_pubmed_pmc
Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis
Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis Abstract Objective In AIDS Clinical Trials Group study A5375, a pharmacokinetic trial of levonorgestrel emergency contraception, double-dose levonorgestrel (3 mg, versu...
PMC11442856
core_pubmed_pmc
Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects
Acute dose-dependent effects of mescaline in a double-blind placebo-controlled study in healthy subjects Abstract Classic psychedelics have regained interest in research and therapy. Despite the long tradition of the human use of mescaline, modern data on its dose-dependent acute effects and pharmacokinetics are lackin...
PMC12311132
core_pubmed_pmc
In silico exploration of anticancer plant phytochemicals for EGFR-targeted lung cancer therapy
In silico exploration of anticancer plant phytochemicals for EGFR-targeted lung cancer therapy Abstract Mutations in the epidermal growth factor receptor (EGFR), particularly in the tyrosine kinase domain such as exon 19 deletions and the L858R point mutation, play a critical role in the development of non-small cell l...
PMC8971662
core_pubmed_pmc
A Combined Pharmacometrics Analysis of Biomarker Distribution Under Treatment With Standard- or Low-Dose Rivaroxaban in Real-World Chinese Patients With Nonvalvular Atrial Fibrillation
A Combined Pharmacometrics Analysis of Biomarker Distribution Under Treatment With Standard- or Low-Dose Rivaroxaban in Real-World Chinese Patients With Nonvalvular Atrial Fibrillation Abstract Background: The rivaroxaban dose regimen for patients with nonvalvular atrial fibrillation (NVAF) is complex in Asia. Given th...
PMC9484173
core_pubmed_pmc
Evaluation of the food effect on a drospirenone only contraceptive containing 4 mg administered with and without high-fat breakfast in a randomised trial
Evaluation of the food effect on a drospirenone only contraceptive containing 4 mg administered with and without high-fat breakfast in a randomised trial Abstract Background The objective of the present trial was to assess the difference in pharmacokinetics (PK) of an oral test preparation containing 4 mg drospirenone ...
PMC7830249
core_pubmed_pmc
Current Limitations and Recent Progress in Nanomedicine for Clinically Available Photodynamic Therapy
Current Limitations and Recent Progress in Nanomedicine for Clinically Available Photodynamic Therapy Abstract Photodynamic therapy (PDT) using oxygen, light, and photosensitizers has been receiving great attention, because it has potential for making up for the weakness of the existing therapies such as surgery, radia...
PMC11315854
core_pubmed_pmc
Retrospective Assessment of Translational Pharmacokinetic–Pharmacodynamic Modeling Performance: A Case Study with Apitolisib, a Dual PI3K/mTOR Inhibitor
Retrospective Assessment of Translational Pharmacokinetic–Pharmacodynamic Modeling Performance: A Case Study with Apitolisib, a Dual PI3K/mTOR Inhibitor Abstract Background and Objectives Despite significant progress in biomedical research, the rate of success in oncology drug development remains inferior to that of ot...
PMC9303875
core_pubmed_pmc
Pharmacokinetic/Pharmacodynamic Evaluation of Ivosidenib or Enasidenib Combined With Intensive Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed IDH1/2 ‐Mutant Acute Myeloid Leukemia
Pharmacokinetic/Pharmacodynamic Evaluation of Ivosidenib or Enasidenib Combined With Intensive Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed IDH1/2 ‐Mutant Acute Myeloid Leukemia Abstract Abstract Mutant isocitrate dehydrogenase 1/2 (mIDH1/2) proteins catalyze production of the oncometabolit...
PMC8105874
core_pubmed_pmc
Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: A current overview of in vivo studies
Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: A current overview of in vivo studies Abstract The management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the va...
PMC11573838
core_pubmed_pmc
Changes in Plasma Clearance of CYP450 Probe Drugs May Not be Specific for Altered In Vivo Enzyme Activity Under (Patho)Physiological Conditions: How to Interpret Findings of Probe Cocktail Studies
Changes in Plasma Clearance of CYP450 Probe Drugs May Not be Specific for Altered In Vivo Enzyme Activity Under (Patho)Physiological Conditions: How to Interpret Findings of Probe Cocktail Studies Abstract Background and objective CYP450 (CYP) phenotyping involves quantifying an individual’s plasma clearance of CYP-spe...
PMC12685190
core_pubmed_pmc
Phase 1, randomized, crossover study comparing intravenous GTX-104 to oral nimodipine in healthy human subjects
Phase 1, randomized, crossover study comparing intravenous GTX-104 to oral nimodipine in healthy human subjects Abstract Enterally-administered nimodipine is the only approved drug formulation available in the United States for treatment of patients with aneurysmal subarachnoid hemorrhage. Intravenous nimodipine is ava...
PMC9804871
core_pubmed_pmc
Effect of Opicapone on Levodopa Pharmacokinetics in Patients with Fluctuating Parkinson's Disease
Effect of Opicapone on Levodopa Pharmacokinetics in Patients with Fluctuating Parkinson's Disease Abstract ABSTRACT Background Inhibiting catechol‐O‐methyltransferase extends the plasma half‐life of levodopa, potentially allowing physicians to optimize the levodopa regimen in patients with Parkinson's disease (PD) expe...
PMC5824121
core_pubmed_pmc
Frequency‐Domain Response Analysis for Quantitative Systems Pharmacology Models
Frequency‐Domain Response Analysis for Quantitative Systems Pharmacology Models Abstract Abstract Drug dosing regimen can significantly impact drug effect and, thus, the success of treatments. Nevertheless, trial and error is still the most commonly used method by conventional pharmacometric approaches to optimize dosi...
PMC8176636
core_pubmed_pmc
Pharmacodynamic Correlates of Linezolid Activity and Toxicity in Murine Models of Tuberculosis
Pharmacodynamic Correlates of Linezolid Activity and Toxicity in Murine Models of Tuberculosis Abstract Abstract Background Linezolid (LZD) is bactericidal against Mycobacterium tuberculosis , but it has treatment-limiting toxicities. A better understanding of exposure-response relationships governing LZD efficacy and ...