Development of a Physiologically-Based Pharmacokinetic Model for Quantitative Interpretation of Transdermal Drug Delivery of Rotigotine, a Dopamine Agonist for Treating Parkinson's Disease.

Background And Objective: Rotigotine, a dopamine agonist, is used to treat Parkinson's disease and restless leg syndrome, with transdermal patches being the primary delivery method in clinical practice. However, quantitative information on the in vivo pharmacokinetics of rotigotine across various dosage regimens via transdermal administration remains limited, and this has been identified as a significant barrier to achieving precision medicine. This study aims to develop a novel physiologically-based systematic pharmacokinetic model tailored to rotigotine transdermal drug delivery.

Association of Right Ventricular-Pulmonary Arterial Coupling and Progression of Tricuspid Regurgitation in Patients With Atrial Fibrillation.

Background: Tricuspid regurgitation (TR) severity is associated with poor prognosis in patients with atrial fibrillation (AF). Recently, right ventricular-pulmonary arterial (RV-PA) coupling has been shown to be related to clinical outcomes in patients with TR. However, data on the relationship of RV-PA coupling to the progression of significant TR are limited.

Exposure risk assessment through toxicodynamics assessment of 4-tert-octylphenol and estimation of new reference values based on human tissue toxicity.

4-tert-Octylphenol (4-tert-OP) is a hazardous substance with ongoing environmental exposure reports, highlighting the need for predictive human toxicity studies. This study aims to propose a new human risk assessment approach for 4-tert-OP by predicting its tissue toxicity using a toxicodynamics (TD) model and linking it to an established physiologically based toxicokinetic (PBTK) model. The TD model for 4-tert-OP was developed based on the results of its toxicity evaluation in human kidney, testis, and liver cell lines.

Considerations of sex in bioequivalence assessments: does sex affect pharmacokinetic variability between evaluation formulations?

Background: Bioequivalence assessment determines the equivalence between drug formulations and is primarily used to demonstrate that a generic product is equivalent to its reference. The sex of the drug consumer is a major consideration in bioequivalence assessment, but specific ratios or absolute criteria for sex composition are usually not specified.

Purpose: This study explored whether the sex of participants in a bioequivalence assessment could significantly affect the pharmacokinetic variability between formulations and decision outcomes.

Electrocardiography-based artificial intelligence predicts the upcoming future of heart failure with mildly reduced ejection fraction.

Background: Heart failure with mildly reduced ejection fraction (HFmrEF) has emerged as the predominant subtype of heart failure (HF). This study aimed to develop artificial intelligence (AI)-electrocardiography (ECG) to identify and predict the prognosis of patients with HFmrEF.

Methods: We collected 104,336 12-lead ECG datasets from April 2009 to December 2021 in a tertiary centre.

The effect of SGLT2 inhibitor in patients with type 2 diabetes and atrial fibrillation.

Background: Sodium glucose cotransporter 2 (SGLT2) inhibitors improve clinical outcomes in several populations including type 2 diabetes (T2D), chronic renal insufficiency, and heart failure (HF). However, limited data exist on their effects on atrial fibrillation (AF).

Methods: We conducted a retrospective cohort study using the National Health Insurance Service database.

Interrelation between hypoxic liver injury and Killip classification in ST-segment elevation myocardial infarction patients.

Introduction: Hypoxic liver injury (HLI) and Killip classification are poor prognostic factors in patients with ST-segment elevation myocardial infarction (STEMI). This study investigates the interrelationship between hypoxic liver injury (HLI) and Killip classification.

Method And Results: A total of 1,537 STEMI patients who underwent percutaneous coronary intervention (PCI) from 2007 to 2014 at four tertiary hospitals in the Incheon-Bucheon province were enrolled in this study.

Pharmacokinetic Prediction of Immediate- and Extended-Release Tablets for Patients with Liver Disease Using Whole Body Physiologically-Based Pharmacokinetic Modeling for the Antipsychotic Drug Quetiapine.

Although quetiapine metabolism occurs extensively in the liver and careful dosing is recommended in patients with liver disease, there has been a paucity of pharmacometric studies to adjust the clinical dose of quetiapine according to liver-disease severity. This study aimed to establish a whole-body, physiologically-based pharmacokinetic (WB-PBPK) model to explain interindividual variability in quetiapine PK and quantitatively predict PK in patients with liver disease. The developed WB-PBPK model well described the PK characteristics of different quetiapine regimens in healthy populations.

Use of artificial intelligence-powered ECG to differentiate between cardiac and pulmonary pathologies in patients with acute dyspnoea in the emergency department.

Background: Acute dyspnoea is common in acute care settings. However, identifying the origin of dyspnoea in the emergency department (ED) is often challenging. We aimed to investigate whether our artificial intelligence (AI)-powered ECG analysis reliably distinguishes between the causes of dyspnoea and evaluate its potential as a clinical triage tool for comparing conventional heart failure diagnostic processes using natriuretic peptides.

Structure-Based Analysis of Cefaclor Pharmacokinetic Diversity According to Human Peptide Transporter-1 Genetic Polymorphism.

Cefaclor is a substrate of human-peptide-transporter-1 (PEPT1), and the impact of inter-individual pharmacokinetic variation due to genetic polymorphisms of solute-carrier-family-15-member-1 () has been a topic of great debate. The main objective of this study was to analyze and interpret cefaclor pharmacokinetic variations according to genetic polymorphisms in exons 5 and 16. The previous cefaclor bioequivalence results were integrated with additional exons 5 and 16 genotyping results.

Quantitative summary on the human pharmacokinetic properties of cannabidiol to accelerate scientific clinical application of cannabis.

Cannabidiol (CBD) is a non-psychoactive substance that exerts numerous pharmacological benefits, including anti-inflammatory and antioxidant properties. It has received attention as a useful substance for the treatment of intractable pain, seizures, and anxiety, and related clinical trials have continued. However, the CBD pharmacokinetic results between reports are highly variable, making it difficult to clearly identify the pharmacokinetic properties of CBD.

Pharmacokinetic Analysis of Levodropropizine and Its Potential Therapeutic Advantages Considering Eosinophil Levels and Clinical Indications.

Levodropropizine is a non-narcotic, non-centrally acting antitussive that inhibits the cough reflex triggered by neuropeptides. Despite the active clinical application of levodropropizine, the exploration of its inter-individual pharmacokinetic diversity and of factors that can interpret it is lacking. The purpose of this study was to explore effective covariates associated with variation in the pharmacokinetics of levodropropizine within the population and to perform an interpretation of covariate correlations from a therapeutic perspective.

Sex differences in 4-tert-octylphenol toxicokinetics: Exploration of sex as an effective covariate through an in vivo modeling approach.

4-tert-octylphenol (4-tert-OP) is a potentially harmful substance, which is found widely in the environment. Nevertheless, information on the in vivo toxicokinetics of 4-tert-OP is lacking, and quantitative risk assessment studies are urgently needed. Therefore, we aimed to quantitatively identify differences in the toxicokinetics of 4-tert-OP and its distribution among tissues between sexes.

P-glycoprotein mechanical functional analysis using in silico molecular modeling: Pharmacokinetic variability according to ABCB1 c.2677G > T/A genetic polymorphisms.

P-glycoprotein (P-gp) is a widely membrane-expressed multi-drug transporter. It is unclear whether the pharmacokinetic diversity of P-gp substrates is highly dependent on ABCB1 polymorphisms encoding P-gp. The purpose of this study is to analyze the mechanistic function of P-gp through in silico molecular modeling and to approach the resolution of controversy over pharmacokinetic differences according to ABCB1 polymorphisms.

Inter-individual exposure variability interpretation through reflection of biological age algorithm in physiologically based toxicokinetic model: Application to human risk assessment of di-isobutyl-phthalate.

Age-related changes and interindividual variability in the degree of exposure to hazardous substances in the environment are pertinent factors to be considered in human risk assessment. Existing risk assessments remain in a one-size-fits-all approach, often without due consideration of inter-individual toxicokinetic variability factors, such as age. The purpose of this study was to advance from the existing risk assessment of hazardous substances based on toxicokinetics to a precise human risk assessment by additionally considering the effects of physiologic and metabolic fluctuations and interindividual variability in age.

Modeling population pharmacokinetics of morniflumate in healthy Korean men: extending pharmacometrics analysis to niflumic acid, its major active metabolite.

This study aimed to quantify and explain inter-subject variability in morniflumate pharmacokinetics and identify effective covariates through population pharmacokinetics modeling. Models were constructed using bioequivalence pharmacokinetics results from healthy Korean males and individual physiological and biochemical parameters. Additionally, we incorporated previously reported pharmacokinetics results of niflumic acid, a major active metabolite of morniflumate, to extend the established population pharmacokinetics model and predict niflumic acid pharmacokinetics.

Quantitative assessment of the relevance of organic-anion-transporting-polypeptide 1B1 and 2B1 polymorphisms in fexofenadine pharmacokinetic variants via pharmacometrics.

Fexofenadine is useful in various allergic disease treatment. However, the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking. This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmacokinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.