Jae-Gook Shin

Jae-Gook Shin
Inje University | inje · Department of Pharmacology and Department of Clinical Pharmacology

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415
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Publications

Publications (415)
Article
Full-text available
Despite remarkable success in the prevention and treatment of tuberculosis (TB), it remains one of the most devastating infectious diseases worldwide. Management of TB requires an efficient and timely diagnostic strategy. In this study, we comprehensively characterized the plasma lipidome of TB patients, then selected candidate lipid and lipid-rela...
Article
Drug-induced nephrotoxicity is frequently reported. However, the mechanisms underlying nephrotoxic medications and their overlapping molecular events, which might have therapeutic value, are unclear. We performed a genome-wide analysis of gene expression and a gene set enrichment analysis to identify common and unique pathways associated with the t...
Article
Full-text available
Standard tuberculosis (TB) management has failed to control the growing number of drug-resistant TB cases worldwide. Therefore, innovative approaches are required to eradicate TB. Model-informed precision dosing and therapeutic drug monitoring (TDM) have become promising tools for adjusting anti-TB drug doses corresponding with individual pharmacok...
Article
In this study, we explored clofazimine (CFZ) as a potential substrate of uptake and efflux transporters that might be involved in CFZ disposition, using transporter gene overexpressing cell lines in vitro. The intracellular concentrations of CFZ were significantly increased in the presence of selective inhibitors of P-gp and BCRP, which include ver...
Article
Pediatric patients with coronavirus disease 2019 (COVID-19) are increasing, and severe cases such as multisystem inflammatory syndrome are being reported. Nafamostat, a repurposing drug, is currently being explored for the treatment of COVID-19 in adults. However, the data supporting its exposure in pediatrics remains scarce. Physiologically-based...
Article
The mechanisms underlying colistin-induced toxicity are not fully understood. This study used untargeted metabolomics and transcriptomics to elucidate the molecular processes occurring in the liver and kidney of rats after treatment with colistin methanesulfonate (CMS). Rats were treated with 50 mg/kg CMS (high-dose), 25 mg/kg CMS (low-dose), or ve...
Article
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Insight into the metabolic biosignature of tuberculosis (TB) may inform clinical care, reduce adverse effects, and facilitate metabolism-informed therapeutic development. However, studies often yield inconsistent findings regarding the metabolic profiles of TB. Herein, we conducted an untargeted metabolomics study using plasma from 63 Korean TB pat...
Article
Full-text available
Objective No population PK model of isoniazid (INH) has been reported for the Indonesian population with tuberculosis (TB). Therefore, we aimed to develop a population PK model to optimize pharmacotherapy of INH based on therapeutic drug monitoring (TDM) implementation in Indonesian TB patients. Materials and methods INH concentrations, N-Acetyltr...
Article
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Background Few studies have annotated the whole mitochondrial DNA (mtDNA) genome associated with drug responses in Asian populations. This study aimed to characterize mtDNA genetic profiles, especially the distribution and frequency of well-known genetic biomarkers associated with diseases and drug-induced toxicity in a Korean population. Method W...
Chapter
Pharmacogenetics has become one of the leading areas of personalized medicine to increase both the prescribed drug’s efficacy and safety. To implement pharmacogenetics into routine clinical practice, genotyping assay needs provide a rapid, simple, reliable and cost-saving method. A number of the kits commercially available contain limited coverage,...
Article
Tuberculosis (TB) is a leading cause of death worldwide and South Korea has the highest incidence and mortality rate of the disease of all the OECD countries. Professor Jae-Gook Shin is a pharmacologist based at the Center for Personalized Precision Medicine of Tuberculosis (cPMTb), which was established based on the premise of adopting a personali...
Preprint
Full-text available
Background: Mitochondrial variants have been investigated to be associated with many diseases, which was reported largely from European populations. Few studies, however, have annotated the whole mitochondrial DNA (mtDNA) genome associated with drug responses including adverse drug reactions (ADRs), especially in Asian populations. This study was p...
Article
The clinical utility of blood transcriptomic biosignatures for the treatment monitoring and outcome prediction of tuberculosis (TB) remains limited. In this study, we aimed to discover and validate biomarkers for pulmonary TB treatment monitoring and outcome prediction based on kinetic responses of gene expression during treatment. In particular, d...
Article
Aim: Tenofovir and para-aminosalicylic acid (PAS) may be co-prescribed to treat patients with concomitant infections of human immunodeficiency virus and Mycobacterium tuberculosis bacteria. Both drugs are known to have remarkable renal uptake transporter-mediated clearance. Owing to the lack of clinical studies on drug-drug interaction between the...
Article
The wide variability of isoniazid (INH) pharmacokinetics is mainly attributed to the trimodal N‐acetyltransferase 2 (NAT2) acetylator phenotype, i.e., rapid, intermediate, and slow. Consequently, a uniform INH dose in the current clinical practice may lead to treatment failure and drug resistance emergence. There is a lack of studies on specific do...
Article
Full-text available
A common cause of drug hypersensitivity reactions is iodinated contrast media (ICM). ICM-induced hypersensitivity had been considered to be a non-immunological reaction, but evidence for an immunological mechanism has increased recently. Thus, we evaluated whether HLA-A, -B, and -C alleles were associated with ICM-induced hypersensitivity. In total...
Article
Accurate metabolome measurements are critical for improved insights into breast cancer metabolic disturbances and enhanced exploration of novel therapeutic targets. Nevertheless, conventional functional interpretation is limited by metabolite identification capacity, which diminishes the scientific value of untargeted metabolomics analyses. In this...
Article
Even though subclasses of macrophage have distinct roles during progression of infectious diseases, it remains poorly understood whether there is a subset-specific difference in drug responses. Here, we report that ABCG2 was expressed specifically in M2-like macrophages and that it controlled their efflux activities. Abcg2 expression is markedly in...
Article
This clinical trial was conducted to evaluate the pharmacokinetics and pharmacodynamics of tegoprazan when coadministered with amoxicillin/clarithromycin in healthy subjects. Cohort 1 was an open-label, randomized multiple-dose study to evaluate the mutual interaction of tegoprazan and amoxicillin/clarithromycin on the disposition of 3 tested drugs...
Article
Full-text available
Phosphodiesterase 3A (PDE3A) is an enzyme that plays an important role in the regulation of cyclic adenosine monophosphate (cAMP)-mediated intracellular signaling in cardiac myocytes and platelets. PDE3A hydrolyzes cAMP, which results in a decrease in intracellular cAMP levels and leads to platelet activation. Whole-exome sequencing of 50 DNA sampl...
Article
Sorafenib was suggested to cause drug-drug interaction (DDI) with the common anticoagulant, warfarin based on published studies. The inhibition on CYP2C9 enzyme was thought to be the mechanism, but further studies are warranted. Thus, a mechanistic PBPK/PD model for warfarin enantiomers was developed to predict DDI potential with sorafenib, aiming...
Article
The objectives of the present study were to identify CYP4V2 genetic variants and characterize their functional consequences. A total of 26CYP4V2 genetic variants were identified, including seven novel variants in 60 randomly selected healthy subjects. Six protein‐coding variants were studied, including three novel variants (L22V, R287T, and G410C)...
Article
Despite quantitative increases and qualitative advances in pharmacogenomics (PGx) research, the clinical implementation of PGx-based personalized therapy has still been limited. The objective of this study was to assess physicians' self-reported knowledge of PGx-based personalized therapy, and to explore the most problematic and highest priority ba...
Article
The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.endend.2014.06.001. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Article
20-hydroxyeicosatetraenoic acid (20-HETE) is an arachidonic acid metabolite which is known to increase platelet aggregation and cardiovascular risk. In this study, nine non-steroidal anti-inflammatory drugs (NSAIDs) selected by chemical structures were screened to determine their effects on the glucuronidation of 20-HETE using human liver microsome...
Article
What is known and objective Although patients may have received vancomycin therapy with therapeutic drug monitoring (TDM), those treated with high‐strength and long‐term vancomycin therapy might have unstable and time‐varying renal function. The methods used to estimate renal function should not be considered interchangeable with pharmacokinetic (P...
Article
Antiepileptic drugs (AEDs) can induce severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. We performed HLA genotyping and lymphocyte activation tests (LATs) for five AED-induced SCAR patients (three males and...
Article
Full-text available
Purpose: The aims of this study was to investigate the mutual pharmacokinetic interactions between steady-state atorvastatin and metformin and the effect of food on the fixed-dose combined (FDC) tablet of atorvastatin and metformin extended release (XR). Subjects and methods: Study 1, an open-labeled, fixed sequence, multiple-dose pharmacokinetic d...
Article
The objective of the present study was to investigate the effects of cytochrome b5 (cytb5) on the drug metabolism catalyzed by CYP2C9, CYP2C19 and CYP3A4. Activities of CYP2C9, CYP2C19, and CYP3A4 were determined by using the prototypical substrates tolbutamide, omeprazole and midazolam, respectively. Cytb5 protein and mRNA contents showed large in...
Article
Full-text available
Objective: The aim of this study was to compare the pharmacokinetic (PK) and safety profiles of a fixed dose combination (FDC) formulation and co-administration of amlodipine, olmesartan, and rosuvastatin. Materials and methods: This study was an open-label, randomized, cross-over design conducted in healthy male volunteers. All subjects received e...
Article
Rifampin (RIF) has been widely used for the treatment of bacterial infections, including tuberculosis (TB). Treatment of drug-resistant TB is a global problem because of reduced drug efficacy. The present study determined the effect of RIF on MDR1 gene (P-glycoprotein, P-gp) expression in THP1 macrophages and analyzed the intracellular concentratio...
Article
Background CT-P16 is a candidate biosimilar of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor that is used in the treatment of a range of advanced solid cancers. Objective The objective of this study was to demonstrate the pharmacokinetic equivalence of CT-P16 and European Union (EU)-approved bevacizumab (EU-bevaci...
Article
Full-text available
Model-informed precision dosing (MIPD) is modeling and simulation in healthcare to predict the drug dose for a given patient based on their individual characteristics that is most likely to improve efficacy and/or lower toxicity in comparison to traditional dosing. This paper describes the background and status of MIPD and the activities at the 1st...
Article
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Background: The effect of drugs on ATP-binding cassette transporters, especially permeability-glycoprotein (P-gp), is an important consideration during new anti-cancer drug development. Objective: In this context, the effects of a newly synthesized artemisinin derivative, 10-(4-phenyl-1H-1,2,3-triazol)-artemisinin (5a), were evaluated on P-gp ex...
Article
The widely used second‐line antituberculosis drug ethionamide shows wide interindividual variability in its disposition; however, the relevant factors affecting this phenomenon have not been characterized. We previously reported the major contribution of flavin‐containing monooxygenase 3 (FMO3) in the reductive elimination pathway of ethionamide. I...
Article
Full-text available
Purpose We evaluated potential drug-drug interactions between cilostazol and simvastatin, both CYP3A substrates, in healthy subjects. Methods An open-label, two-period, fixed-sequence clinical study was conducted. Seventeen subjects were given a single oral dose of simvastatin 40 mg on day 1 and multiple oral doses of cilostazol 100 mg twice daily...
Article
Aims: In vitro study showed that benidipine is exclusively metabolised by cytochrome P450 (CYP) 3A. This study evaluated the effect of rifampin on the enantioselective disposition and anti-hypertensive effect of benidipine. Methods: Benidipine (8 mg) was administered to healthy subjects with or without repeated rifampin dosing, in a crossover de...
Article
Volume 62, no. 9, e00512-18, 2018, https://doi.org/10.1128/AAC.00512-18. Table 2: in the last 2 rows of this table, the [I]/IC50 values were incorrectly listed. For ibuprofen with isoniazid as the substrate, the [I]/IC50 should read 43.6 instead of 16.7, and for probenicid with amoxicillin as the substrate, the [I]/IC50 should read 16.9 instead of...
Article
Objective: The objective of this study was to explore a pharmacogenomic information-based enrichment study design for reducing the sample size in bioequivalence (BE) studies using tolterodine and CYP2D6 genotypes. Materials and methods: A BE study of tolterodine was performed in a randomized, open-label, 2×2 cross-over design. A two one-sided te...
Article
Objective: This study aimed at exploring the effects of metformin on the pharmacodynamics of voglibose, while investigating the pharmacodynamics between a fixed-dose combination (FDC) of voglibose/metformin and coadministered doses of voglibose and metformin tablets in healthy Korean subjects. Materials and methods: A randomized, open-label, 2×3...
Article
Purpose: The aim of this study was to investigate the population pharmacokinetic (PK) profile of meropenem in Korean patients with acute infections. Methods: The study included 37 patients with a creatinine clearance ≤50 or >50 mL/min who received a 500- or 1000-mg dose of meropenem, respectively, infused intravenously over 1 hour every 8 hours....
Article
Substrate potential of antituberculosis drugs on SLC transporters are not well characterized to date, despite a well-established understanding of their drug dispositions and pharmacokinetics. In this study, we investigated comprehensively the substrate potentials of the 22 currently available antituberculosis drugs for solute carrier (SLC) family t...
Article
Currently, ethionamide is the most frequently prescribed second‐line antituberculosis drug in children. After extensive metabolism by flavin‐containing monooxygenase (FMO) isoform 3 in the liver, the drug may exert cytotoxic effects. The comparison of children in different age groups revealed a significant age‐related increase in ethionamide elimin...
Article
Full-text available
Objective The aim of this study was to compare the pharmacokinetics (PK) and safety profiles of a fixed-dose combination (FDC) formulation of fimasartan, amlodipine, and rosuvastatin with the co-administration of the two products by using a replicated crossover study design in healthy male subjects. Results This was an open-label, randomized, thre...
Article
Amiodarone is a class III anti-arrhythmic benzofuran derivative extensively utilized in treatment of life-threatening ventricular and supraventricular arrhythmias. However, amiodarone also produces adverse side effects including liver injury due to its metabolites rather than parent drug. The purpose of the present study was to identify metabolites...
Article
Full-text available
CYP4F2 is an enzyme involved in the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid and metabolizes vitamin K into an inactive form. Our objectives were to identify new CYP4F2 genetic variants and to characterize the functional consequences of the conversion of arachidonic acid into 20-HETE. We used direct DNA sequencin...
Article
Ethionamide (ETA) is the most frequently prescribed oral second-line anti-tuberculosis drugs in children at present. The drug undergoes extensive metabolism by flavin-containing monooxygenase isoform 3 (FMO3) in the liver to exert its cytotoxic effects. In vivo, a significant age-related change in ETA elimination has been observed when comparing di...
Article
BACKGROUND: The aim of this study was to explore the genetic effects of candidate single nucleotide polymorphisms (SNPs) in pharmacokinetics and pharmacodynamics (PKPD) pathway of AP on AP-induced amenorrhea in female schizophrenia patients. METHODS: Eighty nine female schizophrenic patients (age range from 18 to 40) taking the same AP for more tha...
Article
BACKGROUND: The objective of present study was to investigate the effects of cytochrome b5 (cytb5) on the drug metabolism catalyzed by CYP2C9, CYP2C19 and CYP3A4. METHODS: Expression of cytb5 protein and mRNA in human liver tissues was evaluated using Western blot and quantitative real-time PCR, respectively. Genetic polymorphisms in cytb5 gene wer...
Article
BACKGROUND: Sophorae radix has been widely used for the treatment of diarrhea, inflammation, abscess, dysentery, and fevers in Oriental countries. The major ingredients are known as prenylated flavonoids and may cause herb-drug interactions in human. In this study, the inhibition of CYP isoform activities by Sophorae radix extracts were evaluated i...
Article
BACKGROUND: Somatic and hereditary germline mutations to increase the susceptibility to cancers have increased risk for developing cancer. Detection of these mutations in cancer patients can provide great benefits for diagnostics, prediction of prognosis and precision medicine. The objective of this study was to to develope and validated a custom N...
Article
Individual variation in drug response is a major issue in the area of pharmacotherapy and of a drug development. The pharmacological response variation may cause therapeutic failure or adverse drug reactions in patients who have unusual genotype. It has been well known that the inter-individual variation of the pharmacological responses is related...
Article
Full-text available
Objective This study compared the pharmacokinetic (PK) and safety profiles of a fixed-dose combination (FDC) formulation of telmisartan and S-amlodipine with those of concomitant administration of the two drugs. Materials and methods This was an open-label, randomized, crossover study in healthy male Koreans. All subjects were administered an FDC...
Article
Full-text available
This study focused on the role of cytochrome P450 2D6 (CYP2D6) genotypes to predict phenotypes in the metabolism of dextromethorphan. CYP2D6 genotypes and metabolic ratios (MRs) of dextromethorphan were determined in 201 Koreans. Unsupervised clustering algorithms, hierarchical and k-means clustering analysis, and color visualizations of CYP2D6 act...
Article
CYP4F11, together with CYP4F2, plays an important role in the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid. We identified 21 variants by whole exome sequencing, including 4 non-synonymous variants in Korean subjects. The proteins of the wild-type CYP4F11 and the four coding variants (C276R, D315N, D374Y, and D446N) w...
Conference Paper
BACKGROUND: Multidrug-resistant tuberculosis is growing and may be threat among patients infected with human immunodeficiency virus (HIV). Para-amino salicylic acid (PAS), a 2nd line anti-tuberculosis drug, has been recently reported as a strong inhibitor of OAT transporters. Adefovir/tenofovir, used for the treatment of hepatitis B virus and HIV,...
Article
Background Although studies assessing the cost effectiveness of genotype-guided warfarin dosing for the management of atrial fibrillation, deep vein thrombosis, and pulmonary embolism have been reported, no publications have addressed genotype-guided warfarin therapy in mechanical heart valve replacement (MHVR) patients or genotype-guided warfarin...
Article
para-Aminosalicylic acid (PAS) is a second-line anti-tuberculosis drug used to treat multidrug-resistant and extensively drug-resistant tuberculosis for more than 60 years. Renal secretion and glomerular filtration are the major pathways for elimination of PAS. We comprehensively studied PAS transport by using cell lines that overexpressed various...
Article
Full-text available
We investigated population pharmacokinetics (PK) of doripenem in Korean patients with acute infections, and determined an appropriate dosing regimen using a Monte-Carlo simulation for predicting pharmacodynamics (PD). Patients (n = 37) with a creatinine clearance (CLCR) of 20∼50 mL/min or >50 mL/min who received a 250-mg or 500-mg dose of doripenem...