Publications by authors named "Jihun Jang"

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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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Article Synopsis
  • A study investigated genetic variants linked to nonhereditary colorectal polyposis, focusing on 638 patients without known hereditary mutations, using data collected from 2012 to 2021.
  • Genome-wide association study (GWAS) found 71 new single-nucleotide polymorphisms (SNPs) that are potential risk factors for this condition, highlighting five significant genes related to colorectal cancer and introducing two previously unlinked genes.
  • Among the identified SNPs, three were notably associated with a higher risk of polyp recurrence, with the gene ABCC4 being particularly significant for nonhereditary colorectal polyposis.
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  • * It found that the volume of distribution of sertraline was notably linked to estimated glomerular filtration rate (eGFR) and clearance correlated with total protein levels, while the CYP2D6*10 allele did not significantly affect these pharmacokinetic variations.
  • * Model simulations indicated that varying total protein and eGFR levels led to considerable differences in serum concentrations of sertraline, particularly highlighting total protein as a major factor influencing the drug's concentration at steady-state.
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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.

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  • Loxoprofen is commonly used to manage pain and inflammation, but there’s limited research on how it behaves differently among individuals (pharmacokinetics or PK).
  • This study aimed to identify factors that might explain variations in how loxoprofen is processed in the body using a population pharmacokinetic model, which can help refine dosing recommendations.
  • The findings suggested that parameters like body surface area, kidney function (creatinine clearance), and albumin levels significantly influenced loxoprofen distribution and concentration in the bloodstream.
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  • 4-tert-octylphenol (4-tert-OP) is an ecologically harmful substance with a history of human exposure, yet current scientific tools for assessing its risk to humans are inadequate.
  • The study aimed to create a physiologically-based-toxicokinetic (PBTK) model for 4-tert-OP, validated through experiments on male rats and adapted for human application.
  • Results revealed that human reference doses for systemic and reproductive toxicity were calculated at 0.16 mg/kg/day and 1.12 mg/kg/day, respectively, with exposure levels varying significantly among different population groups, indicating varying risk levels and the need for ongoing monitoring.
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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.

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  • The study highlights that differences in physiology and genetics between genders may lead to variations in how drugs are processed in the body, specifically for medications affecting the central nervous system (CNS).
  • Despite this potential for variation, many drugs are still prescribed without considering these gender differences, which may lead to inconsistent effectiveness and side effects.
  • The research conducted revealed significant pharmacokinetic differences between males and females, with many CNS-related drugs showing higher exposure levels in females, emphasizing the need to incorporate gender considerations into precision medicine.
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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.

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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.

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  • There is a lack of information on how levocetirizine affects individuals differently, particularly concerning gender, which is important for its clinical use.
  • This study aims to explore gender differences in how levocetirizine is processed in the body (pharmacokinetics) and its effects (pharmacodynamics) through population modeling.
  • Results indicate that while females experience a higher peak concentration and faster reaction recovery from levocetirizine, the overall differences in drug effects between genders are minimal, suggesting standard dosing may be adequate for both.
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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.

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  • Levodropropizine, a nonopioid cough suppressant, is becoming more popular for treating bronchitis, but there are limited pharmacokinetic studies on it, particularly comparing its various formulations.
  • This study used data from a bioequivalence study of 60-mg immediate release levodropropizine tablets to create a population pharmacokinetic model, finding no significant differences among the immediate release tablets, syrups, and capsules.
  • It also revealed that while the pharmacokinetic profile differed between 90-mg controlled release tablets and immediate release ones, the controlled release tablets showed reduced variability in plasma concentrations, especially when influenced by diet.
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  • Rabeprazole is a proton pump inhibitor used to treat conditions like gastritis and gastric ulcers by reducing stomach acid production; however, there is limited data on how its pharmacokinetics differ between genders.
  • The study aimed to investigate these gender differences in rabeprazole's pharmacokinetics and how they impact its pharmacodynamics by analyzing data from healthy Korean men and women.
  • Findings showed no significant differences in overall drug exposure between genders, but women experienced a delay in absorption and had higher maximum plasma concentrations compared to men, indicating distinct gender effects in how the drug is processed in the body.
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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.

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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.

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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.

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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.

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