Pharmacodynamics - Science topic

Dear Colleagues, We are pleased to invite you to contribute to this Special Issue of Pharmaceutics entitled "Challenges and Trends in Geriatric Pharmacotherapy: Pharmacodynamics, Pharmacokinetics, and Personalized Therapeutic Strategies". By 2050, approximately 1.5 billion people worldwide will be 65 years old or older, which is three times as ma...

Dual antiplatelet therapy is the main pharmacological mechanism used to suppress platelet function in order to prevent thrombotic complications following percutaneous coronary angioplasty. Current studies show that the use of tailored antiplatelet therapy leads to significant clinical improvement after stent implantation. The need to individualize...

Older adults (≥60 years of age) have the highest incidence of status epilepticus (SE) among adults and experience the highest morbidity and mortality. SE incidence increases with age in adulthood. A recent study from Austria estimated an incidence of 89.6/100 000 and 67.6/100 000 person‐years adjusted for age and sex in women and men aged >60 years...

The serotonergic psychedelic N,N‐dimethyltryptamine (DMT) presumably stimulates neuroplasticity in vitro and in vivo, by which it may exert neuroprotective effects during acute ischemic stroke. Since neuroplasticity has been implicated in the mechanism of action of rehabilitative therapy in stroke recovery, a pharmacological augmentation strategy f...

This study aimed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of the ketohexokinase inhibitor LY3522348 in healthy participants. This first-in-human phase 1 study evaluated LY3522348, a highly selective, oral dual inhibitor of human ketohexokinase (KHK) isoforms C and A. The study...

Type I interferon (IFN1) pathway–targeting therapies represent a highly promising class of remedies for the treatment of systemic lupus erythematosus. However, the overall clinical benefit of these compounds is afflicted by marked variability. In this study, we developed a quantitative systems pharmacology model of type I IFN‐mediated inflammation...

Background and Purpose Recently, there has been increased research on treatments that modulate the complement system because of its significance in many diseases. However, managing patients with complement‐related diseases is challenging owing to the different responses to treatments because of the heterogeneity of the aetiology of the different di...

Introduction In the era of targeted therapies, molecules for the reactivation of the oncosuppressor p53 in human cancer have not yet reached FDA or EMA approval. Recently, the interaction region of the MDM2/MDM4 heterodimer, the most efficient inhibitor of p53 levels and function, has been successfully targeted. Disruption of the heterodimer activa...

Background and Purpose Understanding of the insulin‐mediated effects on signalling and metabolism is important not only for fundamental knowledge of insulin's action in the brain but also for elucidating the mechanism of therapeutic potential in neurodegenerative disorders with underlying brain metabolic dysfunction. One of the main goals of this r...

Seaweeds are rich in bioactive compounds that contribute to overall health and may reduce the risk of chronic diseases when consumed regularly as part of a balanced diet. Seaweeds have garnered significant attention for their potential as natural sources of anticancer agents, particularly in the treatment of colorectal cancer (CRC). Beyond their th...

Papillary thyroid carcinoma (PTC) is the main type of malignant tumor of the thyroid gland in adults. Huaier, a traditional Chinese medicinal agent, has demonstrated antitumor efficacy across diverse malignant neoplasms. However, the specific impact of huaier in PTC remains insufficiently elucidated. In this study, we explored the function of huaie...

Background Interferons (IFNs) are proteins that combat viruses and regulate the immune system. Studies have demonstrated that aerosol inhalation of IFNα is both effective and safe for treating respiratory infections. However, IFNα has a short half-life and is rapidly cleared by lung defenses. Polyethylene glycol (PEG) ylation is a common strategy t...

Clinical development of novel antiseizure medications (ASMs) would benefit from an early proof of principle (POP) model. The photosensitivity model, which uses the photoparoxysmal electroencephalographic response (PPR) as a surrogate of seizures, is currently the only human model that allows POP trials of investigational compounds after a single dr...

Background Despite the high prevalence of social and performance anxiety, current treatments do not meet the full needs of patients. Development of novel anxiolytics with rapid onset of action for on-demand treatment of social and performance anxiety is an active area of clinical research. Aims To examine the anxiolytic effect of VQW-765, an α7-nA...

Intraperitoneal lidocaine is an emerging strategy for analgesia following abdominal surgery but its pharmacokinetics are poorly quantified. We aimed to develop a pharmacokinetic model for unbound and total lidocaine by intraperitoneal and intravenous routes. Unbound and total lidocaine concentrations, and pain scores (visual analogue score 0–10) we...

Insulin therapy is essential for helping diabetic patients manage their blood glucose levels. Over the years, various insulin analogs with distinct pharmacokinetic and pharmacodynamic profiles have been developed, offering a range of therapeutic options. Rapid-acting insulins, such as insulin lispro, insulin aspart and insulin glulisine, and long-a...

Introduction Optimizing vancomycin dosing in neonates is a critical yet complex goal. Traditional trough concentration-based dosing strategies correlate poorly with therapeutic efficacy and often fail to account for the significant renal function variability and drug clearance in neonates. The 24-hour area under the concentration-time curve to mini...

Rheumatoid arthritis (RA) is a classic autoimmune disease caused by a combination of genetic and environmental factors. The multiple and comprehensive pathologies involving the whole body’s immune system and local organs and tissues make it challenging to control or cure them clinically. Fortunately, there are increasing reports that multiple non-t...

Artificial Intelligence (AI) is transforming the drug development and Clinical Trials by improving efficiency, accuracy, and decision-making. AI predicts Pharmacokinetic (PK) and Pharmacodynamic (PD) properties, automates compound screening and enhances clinical testing throughput. In trial design, AI optimizes patient stratification and outcome pr...

To address the quality instability of the traditional fermentation process of Massa Medicata Fermentata (LSQ), we designed an innovation strategy for dual-strain co-fermentation LSQ. Rhizopus arrhizus, Bacillus velezensis, Bacillus subtills, and Bacillus cereus were selected as the fermentation strains for the LSQ. After dual-strain co-fermentation...

Background and Purpose The JAK–STAT signalling pathway has been extensively spotlighted as a therapeutic target for various diseases. This study assessed the inhibitory effects of a novel small molecule, IN‐115314, on JAK–STAT pathway. Experimental Approach The IC50 values of IN‐115314 for JAK1–pSTAT3 and JAK2–pSTAT5 were determined in canine whol...

Artemisinin-based combination therapies (ACTs) constitute the principal strategy for combating malaria in contemporary times, and research into the multifaceted components of Artemisia annua L. (A. annua) has garnered widespread interest among scientists. The aim of this study was to prepare A. annua extracts (nACTs) and to explore whether nACTs ha...

Based on the phase I/II MajesTEC-1 study, the B-cell maturation antigen (BCMA) and cluster of differentiation (CD)3 bispecific antibody, teclistamab, is approved for relapsed/refractory multiple myeloma (RRMM) at a dose of 1.5 mg/kg weekly (QW), with the option to switch to 1.5 mg/kg every other week (Q2W) in patients maintaining complete response...

Treatment of animals with infectious diseases is associated with certain warnings and difficulties associated with determining the sensitivity of pathogens, progressive clinical signs, and acquired antimicrobial resistance to certain pathogens. Considering animal specifics administering veterinary medicinal products, there is a requirement for fixe...

Objectives Cefiderocol has emerged as a key treatment for managing MDR infections, and its time-dependent pharmacodynamics are optimized by prolonged infusion to maintain time above the MIC (T > MIC). Whereas recent stability studies have shown cefiderocol remains stable up to 72 h in elastomeric pumps, its use in 24 h continuous infusions (CIs) fo...

Standard pharmacodynamic models are ordinary differential equations without the features of stochasticity and heterogeneity. We develop and analyse a stochastic model of a heterogeneous tumour-cell population treated with a drug, where each cell has a different value of an attribute linked to survival. Once the drug reduces a cell’s value below a t...

Develop a novel coupled PK-PD model and apply it to quantitatively evaluate the synergistic effects of Hydroxysafflor Yellow A (HSYA) combined with Calycosin (CA) in the treatment of ischemic stroke. A total of 6 rats were modelled for middle cerebral artery occlusion (MCAO). Plasma was collected from the submandibular venous plexus of rats after t...

KRAS mutations are prevalent in brain metastases (BM) from non-small cell lung cancer (NSCLC). The activity of KRAS-G12C selective, brain-penetrant small molecule inhibitor adagrasib was recently demonstrated in preclinical models of BM and patients with BM carrying KRAS-G12C, leading to a clinical trial investigating this therapeutic approach. How...

Vonoprazan is a potassium competitive acid blocker, has shown potential used to treat acid reflux and eliminating Helicobacter pylori. Its enhanced anti-secretory action, quick action, and reduced anti-secretory variability make it a more suitable option than PPIs. However, many researches are needed to fully understand the effects and its safety a...

The development of therapeutic antibodies requires optimizing target binding affinity and pharmacodynamics, while ensuring high developability potential, including minimizing non-specific binding. In this study, we address this problem by predicting antibody non-specificity by two complementary approaches: (i) antibody sequence embeddings by protei...

Molecular communication (MC), an innovative paradigm leveraging molecules as information carriers, is gaining traction in the biomedical field, particularly in the context of the Internet of Bio-Nano Things (IoBNT) for targeted drug delivery (TDD) systems. Specifically, the transportation of drug molecules in blood vessels is described as the propa...

This scoping review aimed to summarise all available population pharmacokinetic models of morphine and its metabolites (morphine-3-glucoronide [M3G], morphine-6-glucoronide [M6G]) in children and describe how morphine exposure varies across paediatric age groups and settings. Identifying the factors that contribute to pharmacokinetic variability ma...

Aberrant farnesoid X receptor (FXR) signaling is implicated in cholestatic, inflammatory, and fibrotic liver diseases. In preclinical/clinical studies, semisynthetic bile acid‐derived FXR agonists markedly improved hepatic function in various conditions. INT‐787, a novel hydrophilic semisynthetic bile acid FXR agonist, has demonstrated a reduction...

Purpose The daily administration of recombinant human growth hormone (rhGH) replacement therapies via subcutaneous (SC) injections can be burdensome for patients. Long-acting Growth hormone (GH) formulation could reduce injection frequency, and it will be expected to increase treatment adherence. ZHB111 is a PEGylated rhGH that requires sc injectio...

Background The success of passive immunotherapies targeting Calcitonin gene-related peptide (CGRP) for managing migraine has prompted our efforts towards developing an active immunotherapy that induces the production of endogenous antibodies against CGRP. Achieving efficacious antibody titers via immunization could provide a more convenient and cos...

This phase 1 dose-escalation study evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of K1-70TM, a TSH-receptor-specific monoclonal autoantibody that inhibits ligand binding and receptor activation, in Japanese Graves’ disease (GD) patients. Twelve patients were enrolled, divided into four dosage cohorts (5 mg, 25...

Biling Weitong Granules (BLWTG) is a clinical formula employed for treating epigastric pain, yet its pharmacodynamic components and mechanisms against chronic gastric ulcers (GU) remain inadequately understood. The objective of this study was to investigate the targets and mechanisms of BLWTG and its bioactive components in chronic GU. Chronic GU m...

Uncommon EGFR mutations constitute 10%–20% of all EGFR mutations in non‐small cell lung cancer (NSCLC), forming a molecularly distinct and clinically heterogeneous subgroup. This retrospective cohort study evaluated the efficacy and safety of furmonertinib in managing central nervous system (CNS) metastases among NSCLC patients with uncommon EGFR m...

The objective of this study is to develop an artificial intelligence-physiologically based pharmacokinetic (AI-PBPK) model to predict the pharmacokinetic (PK) and pharmacodynamic (PD) properties of aldosterone synthase inhibitors (ASIs), enabling selection of the right candidate with high potency and good selectivity at the drug discovery stage. On...

In medication discovery, Pegylation the covalent attachment of polyethylene glycol (PEG) chains to biomolecules including proteins, peptides, or nucleic acids-has emerged as a key tactic. This alteration improves the therapeutic medicines' pharmacokinetic and pharmacodynamic characteristics, providing increased bloodstream solubility, stability, an...

Respiratory syncytial virus (RSV) remains a significant health concern, particularly for vulnerable populations. Despite preventive strategies, there remains a need for effective antiviral treatments. EDP‐323 is a first‐in‐class, potent oral selective non‐nucleoside inhibitor of the large protein (L polymerase) of RSV under investigation for the tr...

Background/Objectives: Antibody-based therapies often exhibit limited distribution within solid tumors due to the “binding-site barrier” (BSB). Our group has developed and validated the use of anti-idiotypic distribution enhancers (AIDEs), which transiently block antibody binding, improving intra-tumoral distribution and efficacy. This study evalua...

Aims Choice of first‐in‐human dose has critical implications for the safety of Phase I participants as well as the likelihood of reaching the therapeutic dose range during escalation. In this analysis, we present a population concentration–response modelling approach for selecting the Phase I starting dose for a novel stimulator of interferon respo...

Oregano oil was successfully encapsulated into chitosan–albumin nanogel via emulsification and electrostatic gelation. The system was characterized with a mean diameter around 26 nm, narrow size distribution (PDI = 0.242) and approximately 40% encapsulation efficiency. The incorporation of the oil into the nanogel was confirmed by XRD and FTIR anal...

Background Acute myeloid leukemia (AML) is characterized by clonal expansion of myeloid precursors, often accompanied by poor prognostic outcomes in older populations due to molecular heterogeneity and resistance to conventional chemotherapeutic agents. Glasdegib, a potent inhibitor of the Hedgehog signaling pathway, has emerged as a targeted agent...

Recent advancements in nanotechnology have significantly advanced nanocarrier-mediated drug delivery systems, promoting therapeutic outcomes in mitigating chronic inflammation and cancer. Nanomaterials offer significant advantages over traditional small-molecule drugs, including a high surface-area-to-volume ratio, tunable structural features, and...

Os glicocorticóides tópicos são amplamente utilizados na dermatologia para tratar diversas condições cutâneas, devido às suas propriedades anti-inflamatórias, imunossupressoras e vasoconstritoras. A comprovação da bioequivalência desses medicamentos é essencial para garantir que as formulações genéricas e similares apresentem a mesma eficácia e seg...

Understanding cellular transport is essential for delving into the internal functioning of biological systems and how they interact with external agents such as drugs, toxins, and molecular signals. Biotransport systems help explore how cells regulate the exchange of vital substances through complex and highly specialized mechanisms. In this journa...

Previous pharmacogenetic findings for beta‐blocker pharmacodynamic candidate genes (ADRB1, ADRB2, ADRA2C, GRK4, and GRK5) have been inconsistent. Therefore, the purpose of this study was to determine whether interactions of pharmacodynamic variants with beta‐blocker exposure significantly associated with survival in patients with heart failure with...

Mosunetuzumab, a CD20 × CD3 T‐cell‐engaging bispecific antibody, redirects T cells to eliminate malignant B cells. The purpose of YO43555 was to assess the pharmacokinetics (PK), safety, tolerability, and efficacy of mosunetuzumab as a single agent in Chinese patients with relapsed/refractory follicular lymphoma (R/R FL). The impact of ethnicity/re...

Purpose An increasing number of critically ill patients receive slow extended daily dialysis (SLEDD) due to their pathophysiology while suffering from sepsis, necessitating effective and safe antibiotic therapy. Although SLEDD reduces meropenem exposure and increases treatment failure risk, effective and safe dosing regimens are unclear. We aimed t...

Background: Biomarkers with clear contexts-of-use are important tools for ALS therapy development. Understanding their longitudinal trajectory in the untreated state is key to their use as potential markers of pharmacodynamic response. To this end, we undertook a large-scale proteomic study in well-phenotyped cohorts to identify biomarker candidate...

Objective This study aimed to investigate the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of a novel anti-nerve growth factor (NGF) monoclonal antibody (mAb) (AK115) in healthy Chinese participants. Methods A randomized, double-blind, placebo-controlled, dose-escalation phase I clinical study was conducted as follows:...

Marburg Virus (MARV) presents a significant threat to human health, highlighting the urgent need for effective therapeutics. The MARV genome encodes a multifunctional ‘large’ L protein that plays a crucial role in polymerase, capping, and methyltransferase activities. Within this protein, the 2′-O-methyltransferase (2′-O-MTase) domain is essential...

Targeted protein degraders that recruit the von-hippel Lindau E3-ligase complex often have poor physicochemical properties, requiring extensive medicinal chemistry optimization prior to use in hypothesis-testing experiments in vivo, and with few blood-brain-barrier permeable examples disclosed. In this study, we systematically examine a panel of fa...

Medicinal plants have long been central to traditional healthcare systems across civilizations, offering a rich source of bioactive compounds for therapeutic use. In recent years, the focus has shifted from single-plant remedies to synergistic plant combinations, where the joint action of phytochemicals enhances efficacy, reduces toxicity, and broa...

Meropenem dosing to achieve therapeutic exposure in critically ill children with sepsis is challenging due to a spectrum of renal function, from augmented renal clearance (ARC) to acute kidney injury (AKI). The objective of this study was to define meropenem plasma concentrations and pharmacodynamic exposure metrics in children with septic shock du...

Background Smilax glabra Roxb (SGR) is a traditional Chinese medicine known for its medicinal and edible properties, with a long history of clinical use in treating hyperuricemia (HUA). However, current research has primarily focused on ethanol extracts, leaving the active ingredients and mechanisms responsible for the uric acid-lowering effects of...

We examined the association of selected candidate pharmacodynamic (PD) genes in MDD with treatment outcomes, defined according to remission thresholds for Hamilton Depression Rating Scale (HDRS) with 6- and 17- items. To this end, we recruited 158 individuals living with MDD followed in an academic community mental health center. We reconstructed t...

Context Matrine has antinociceptive properties, and spinal cord ionomic changes are involved in bone cancer pain. Objective To investigate the relationship between ionomic metabolism in cerebrospinal fluid (CSF) and spinal cord and matrine’s analgesic efficacy. Materials and methods The antinociceptive effects of matrine were identified in rats v...

Proteome-wide scale in a dose – and time-depending setting is crucial to fully understand the pharmacological mechanism of anticancer drugs as well as identification of candidates for drug response biomarkers. Here, we investigated the effect of the CIGB-300 anticancer peptide at IC 50 and IC 80 doses during 1 and 4 h of treatment on the squamous l...

Fepixnebart (LY3016859), a humanized immunoglobulin G4 monoclonal antibody with high binding affinity to epiregulin and tumor growth factor-α, is being developed as a novel analgesic to treat broad-spectrum chronic pain. Early phase clinical studies demonstrated fepixnebart has nonlinear pharmacokinetics in healthy subjects and patients with diabet...

Non‐invasive, in vivo quantitative imaging for long‐term biomarker monitoring is crucial for elucidating disease mechanisms, advancing precision medicine, and transforming diagnostics and therapeutic strategies. However, developing chemical sensors for sustained in vivo quantitative monitoring despite sensor concentration fluctuations, excitation v...

Purpose: Castration and enzalutamide induce BCL-2 to drive therapy resistance in prostate cancer (PCa). We conducted a phase Ib trial to test that metastatic castration-resistant PCa (mCRPC) can be effectively targeted by combining enzalutamide with the BCL-2 inhibitor venetoclax. Experimental Design: This phase Ib single-arm trial of enzalutamide...

Oxy‐bromination of cyclic amines to corresponding α,α’‐dibromocycloamide(s) using bromide‐bromate couple in aqueous acetic acid and at 60 °C (oil bath) is presented in the current work. A various types of cyclic amines were successfully oxybrominated during this work. Separation of the desired product by filtration therefore avoiding need of column...

Objective: To reveal the metabolic targets, and elucidate the pharmacodynamic material basis in vivo and the mechanism of Dachengqi Decoction (大承气汤) based on its effectiveness in the intervention of colorectal cancer. Methods APCMin/+ mice were used to replicate the colorectal cancer model, the animal model and intervention effect of Dachengqi Dec...

Some scientists and celebrities have labeled homeopathy as pseudoscience due to a dearth of fundamental data supporting the efficacy of homeopathic medicines. The majority of homeopathic physicians feel that clinical trials will suffice for homeopathy research. However, the pharmacokinetics and pharmacodynamics of homeopathic medicines cannot be el...

This study investigated the therapeutic mechanism of Rehmanniae Radix Praeparata (RRP) in treating blood deficiency syndrome (BDS) through integrated chemical analysis and pharmacological validation. UPLC-Q-TOF-MS identified chemical components of Rehmanniae Radix (RR) and RRP, with network pharmacology analysis suggesting AKT1 and NOS3 in the PI3K...

A formulation or apparatus that facilitates the entrance of a medicinal material into the body and enhances its safety and efficacy by regulating the rate, timing, and location of drug release into the body is known as a drug delivery system (DDS). One essential aspect of contemporary medicine that has changed dramatically over time is drug distrib...

Fluorine has become an essential element in the development of modern pharmaceuticals, due to its unique chemical properties that can significantly enhance the biological activity, metabolic stability, and lipophilicity of drug molecules. This review explores recent advancements in the synthesis and application of fluorine‐containing drugs approved...

The adaptation of the body when exposed to a lower-than-usual temperature is a challenge that involves neuro-endocrine–immune mechanisms and affects the pharmacokinetics and/or pharmacodynamics of drugs taken before or after cold exposure. The experiments presented in this study clearly show differences in the analgesic effect of an exogenously int...

DBPR108 (prusogliptin) is a novel, orally bioavailable dipeptidyl peptidase-4 (DPP‐4) inhibitor. This study investigated the pharmacokinetics and pharmacodynamic characteristics of DBPR108 tablets in patients with type 2 diabetes. In this randomized, parallel-group, open-label, phase I study, Chinese adults with type 2 diabetes, glycated hemoglobin...

On February 27, 2025, WHO maintained monkeypox as a PHEIC following its third round of assessment. Human monkeypox virus infection primarily manifests with fever, lymphadenopathy, and rash. Severe cases may develop pneumonia, encephalitis, myocarditis and arthritis. After evaluation of three murine models (ICR, IFNAR1 −/− , and SCID), we identified...

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, approximately one-third of whom are resistant to current anti-seizure drugs (ASDs). Retigabine (RTG) is a potential treatment for treating drug-resistant epilepsy and KCNQ2-related developmental and epileptic encephalopathy (KCNQ2-DEE). However, its use is limited by s...

This book presents a comprehensive, evidence-based scientific analysis of Swarnaprashana. Insight from classical Ayurvedic texts and integrating findings from contemporary biomedical research critically examines the safety, efficacy, pharmacodynamics, and nanomedicine potential of Swarna Bhasma. The work emphasizes standardization, cytotoxicity, an...

The cause of biological death in warm-blooded animals and humans is hypoxic brain cell damage. Consequently, oxygen gas is the leading antihypoxant in emergency medical care for all critical conditions. The most common method of oxygen administration is mechanical ventilation. However, in cases of asphyxia caused by airway obstruction with thick sp...

Objective Quantitative systems pharmacology (QSP) is widely used to assess drug effects and toxicity before the drug goes to clinical trial. However, significant manual distillation of the literature is needed in order to construct a QSP model. Parameters may need to be fit, and simplifying assumptions of the model need to be made. In this work, we...

Background and objectives: IV-administered ocrelizumab (OCR) is approved for the treatment of relapsing and primary progressive multiple sclerosis (RMS/PPMS). OCARINA II (NCT05232825) was designed to demonstrate noninferiority in drug exposure of OCR subcutaneous (SC) vs IV administration. Methods: This phase 3, randomized, open-label study enro...

Background: Achieving pharmacokinetic/pharmacodynamic (PK/PD) targets is critical for improving treatment success, particularly in critically ill patients. This study investigates the role of inflammatory biomarkers and their influence on the PK/PD characteristics of polymyxin B (PMB) in patients with extensively drug-resistant Gram-negative (XDR-G...