Jin-Gyu Jung

Background/Objectives: Mammography remains central to breast cancer diagnosis, yet clinically meaningful uncertainty persists in women with dense breasts and in patients with very small lesions or indeterminate imaging findings. We evaluated whether circulating thioredoxin 1 (Trx1) could provide biological information that complements imaging-based assessment. Methods: This multicenter clinical validation study evaluated circulating Trx1 in 1901 serum samples across four predefined cohorts. Diagnostic performance was assessed using receiver operating characteristic (ROC) and precision–recall analyses, together with evaluation of integration with mammographic assessment and decision curve analysis (DCA). A predefined Trx1 cutoff established in prior clinical investigations was applied. Results: Circulating Trx1 concentrations were significantly elevated in breast cancer compared with controls (p < 0.001). Trx1 showed excellent diagnostic discrimination (AUC 0.985; 95% CI, 0.974–0.996), with sensitivity and specificity of 96.4% and 97.3%, respectively. Diagnostic performance was consistent across disease stages, tumor-size categories, molecular subtypes, mammographic categories, and breast-density groups. Trx1 sensitivity remained high in dense breasts (98.9% in BI-RADS density grades C/D), whereas mammographic sensitivity was substantially lower (67.0%). Integration of Trx1 with mammographic assessment improved diagnostic discrimination (AUC 0.980) and provided greater net benefit in decision curve analysis, particularly among women with low-suspicion or indeterminate imaging findings. Conclusions: Circulating Trx1 demonstrated robust diagnostic performance across disease stages, tumor-size categories, and clinically relevant patient subgroups while providing biologically independent information that complements mammographic assessment. Although this retrospective multicenter study requires prospective validation in independent diagnostic populations, Trx1 may serve as a clinically useful adjunct to imaging-based breast cancer evaluation, particularly in diagnostically uncertain settings.

Background/Objectives: Oral donepezil, an acetylcholinesterase (AChE) inhibitor for Alzheimer’s disease, faces adherence challenges. Long-acting injectable (LAI) formulations like GB-5001 aim to enhance adherence by reducing dosing frequency. This Phase 1, open-label, active-controlled, dose-escalation study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GB-5001 in healthy male adults. Methods: Participants were assigned to cohorts receiving GB-5001A or GB-5001D (LAI formulations) via intramuscular (IM) or subcutaneous (SC) injection, or oral Aricept^®. Safety, PK, and PD (AChE inhibition) were assessed. The influence of CYP2D6 phenotype was explored, and modeling/simulation was performed. Results: Fifty healthy male participants completed the study. After IM administration, GB-5001A (70 mg, 140 mg, 280 mg) showed dose-dependent increases in exposure (AUC_inf and C_max), resulting in significantly extended exposure compared to oral Aricept^® 10 mg. No serious adverse events were reported; the most common AEs were mild injection site reactions, which occurred in all treatment groups except the GB-5001A IM 70 mg group and the Aricept group. GB-5001A also demonstrated sustained AChE inhibition. Conclusions: GB-5001A, an LAI donepezil, showed favorable safety, dose-proportional PK, and sustained plasma exposure. It achieved a 3–4-fold longer half-life than oral donepezil. These findings, supported by modeling, highlight GB-5001A’s potential as a once-monthly IM alternative for Alzheimer’s disease treatment.

Kim CJ, et al. Transl Clin Pharmacol. 2025 Mar;33(1):19-26. https://doi.org/10.12793/tcp.2025.33.e2

Background: Osteoarthritis (OA) is a prevalent joint disease affecting the spine, hands, hips, knees, and feet. However, definitive drugs for OA are lacking, and current treatments are limited owing to inconvenient administration, inadequate functional improvement, and long-term side effects including gastrointestinal and cardiovascular adverse events. Therefore, in this study, we aimed to assess the pharmacokinetics and safety profiles of PK101, a fixed-dose combination (FDC) comprising PG201, a 12-herb extract used in OA treatment in traditional East Asian medicine, and celecoxib, a selective cyclooxygenase-2 inhibitor, by comparing its administration as an FDC and the corresponding individual formulations in healthy subjects. Patients and methods: A randomized, open-label, single-dose, 2 × 2 crossover design with a cohort of healthy participants. All subjects received a single FDC tablet (405.4 mg PG201 and 100 mg celecoxib) or the individual formulations, with 7-day washout period between administrations. The estimation of maximum plasma concentration and area under the plasma concentration–time curve from time zero to the time of the last quantifiable concentration of celecoxib involved determining the geometric mean ratios and 90% confidence intervals of the FDC compared to its individual formulations. Results: Forty-six participants were enrolled; however, only 44 completed the study. The geometric mean ratios (90% confidence intervals) for the area under the plasma concentration–time curve from time zero to the time of the last quantifiable concentration and maximum plasma concentration of celecoxib were 1.1124 (1.0601–1.1672) and 1.2788 (1.1708–1.3969), respectively. The time of maximum plasma concentration range was 1.0 to 4.0 hours and 1.0 to 6.0 hours (minimum–maximum) for the FDC and individual formulations, respectively. Seven adverse events occurred in 6 subjects. Conclusion: The systemic exposure and safety profiles of the individual and FDC formulations were similar, supporting their potential as an innovative and effective therapeutic approach for OA treatment. All relevant data are within the paper and its Supporting Information files.

Background and Objectives Cilostazol improves ischemic symptoms and prevents recurrence following cerebral infarction, and rosuvastatin reduces cholesterol levels. However, no reports exist on the pharmacokinetic interactions between these two drugs in healthy adults. This study evaluated the pharmacokinetic (PK) interactions and safety of cilostazol and rosuvastatin when co-administered to healthy male participants. Methods A randomized, open-label, multiple-dosing, two-arm, two-period study was conducted. Arm A had 30 participants receiving 200 mg cilostazol daily and arm B had 27 participants receiving 20 mg rosuvastatin daily for 7 days. In period 2, both arms received a combination of 200 mg cilostazol and 20 mg rosuvastatin daily for 7 days following a 7-day washout period. Plasma concentrations of cilostazol, its metabolites, and rosuvastatin were quantified using liquid chromatography–tandem mass spectrometry. Results Fifty-seven participants were randomized, and 44 completed the study. The geometric mean ratio (GMR) and 90% confidence intervals (CI) for maximum plasma concentration at steady state (C_max,ss) and area under the plasma concentration–time curve during the dosing interval at steady state (AUC_tau,ss) indicated no significant interaction between cilostazol and rosuvastatin. Safety assessments showed comparable profiles to individual drug administration, with no significant adverse events. Conclusion The repeated co-administration of cilostazol and rosuvastatin in healthy male participants resulted in minor PK interactions and exhibited a safety and tolerability profile similar to those of the individual drugs. This suggested that the combined regimen is well tolerated and does not necessitate dose adjustments. Registration ClinicalTrials.Gov identifier no. NCT06568133.

CT‐P13, a biosimilar of infliximab, is used to treat inflammatory diseases that arise from immune system complications, resulting in excessive and persistent inflammation. The subcutaneous (SC) formulation of CT‐P13 overcomes the drawback of prolonged administration associated with the intravenous (IV) infliximab biosimilar, necessitating autoinjector (AI) administration. This randomized, open‐label, two‐arm, parallel‐group, single‐dose clinical pharmacology study aimed to evaluate the pharmacokinetics (PK) and safety of CT‐P13 SC administration via AI compared with the existing pre‐filled syringe (PFS) method. A total of 147 healthy participants were randomized into two groups, of which 139 completed the study. Blood samples were collected from before CT‐P13 SC administration to 2016 h after the start of the administration. Serum concentrations were analyzed using the Meso Scale Discovery electrochemiluminescence method. Geometric mean ratios (90% confidence interval) of the AUC_inf (areas under the concentration–time curve from zero to infinity) and C_max (The maximum serum concentration) for CT‐P13 SC AI versus CT‐P13 SC PFS groups, were 94.15% (85.02%–104.26%), 92.48% (84.66%–101.01%), respectively. CT‐P13 SC AI and CT‐P13 SC PFS achieved comparable PK because the 90% CI was within the predefined equivalence margin. At the end of the study, immunogenicity results revealed that 70 (97.22%) and 73 (98.65%) participants tested positive for anti‐drug antibody (ADA) in the CT‐P13 SC AI and CT‐P13 SC PFS groups, respectively. They were tested positive for neutralizing antibodies. No other significant safety differences were observed between the treatment groups. In conclusion, both administrations demonstrated PK equivalence and were both safe and well‐tolerated.

Introduction Fixed-dose combinations (FDCs) of angiotensin II receptor blockers, calcium channel blockers, and statins are conventional therapeutic interventions prescribed for cardiovascular diseases. This study aimed at drawing a comparison between the pharmacokinetics and safety of an FDC and the corresponding individual formulations in healthy subjects. Methods A randomized, open-label, single-dose, three-sequence, three-period, partially repeated crossover study was conducted with a cohort of healthy volunteers. A 14-day washout period was maintained between each of the three periods. In this study, candesartan cilexetil, amlodipine, and atorvastatin was administered orally as FDCs of 16/10/40 mg in study 1 and 16/5/20 mg in study 2. The maximum plasma concentration (C_max) and area under the plasma concentration–time curve from time zero to the time of the last quantifiable concentration (AUC_last) of candesartan, amlodipine, and atorvastatin were estimated as the geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the FDC to individual formulations. If the within-subject coefficient of variation (CV_wr) of C_max was greater than 0.3, the bioequivalence (BE) range calculated using the reference-scaled average bioequivalence was used to assess whether the 90% CI was within the BE range. Results The GMRs (90% CIs) for the AUC_last for candesartan and amlodipine were 0.9612 (0.9158–1.0089)/0.9965 (0.9550–1.0397) and 1.0033 (0.9800–1.0271)/1.0067 (0.9798–1.0344), and the GMRs (90% CIs) for C_max were 0.9600 (0.8953–1.0294)/0.9851 (0.9368–1.0359) and 1.0198 (0.9950–1.0453)/1.0003 (0.9694–1.0321) in studies 1 and 2, respectively. The extended BE ranges calculated from the CV_wr of the C_max of atorvastatin were 0.7814–1.2797 and 0.7415–1.3485, respectively. The GMRs (90% CIs) for the AUC_last of atorvastatin were 1.0532 (1.0082–1.1003)/1.0252 (0.9841–1.0680), and the GMRs (90% CIs) for C_max were 1.0630 (0.9418–1.1997)/0.9888 (0.8792–1.1120) in studies 1 and 2, respectively. Conclusion The C_max and AUC_last values of candesartan cilexetil/amlodipine/atorvastatin 16/10/40 mg and 16/5/20 mg, respectively, were within the BE ranges. There were no clinically significant differences in safety between the two formulations. Trial Registration ClinicalTrials.gov identifier, study 1: NCT04478097; study 2: NCT04627207.

Background: In clinical practice, primary healthcare physicians commonly encounter patients with alcohol-related problems. This review article introduces the concept of an alcohol clinic for treating patients with these issues at primary healthcare clinics.Current Concepts: Alcohol-related problems often give rise to health problems, which prompts primary healthcare physicians to be required to develop screening, treatment, and counseling skills. Primary healthcare clinics should actively screen for alcohol-related problems. Screening involves questions regarding the frequency, quantity, and maximum consumption of alcohol to determine risk levels. For Koreans, moderate alcohol consumption is defined as ≤8 drinks per week (1 drink=14 g of alcohol) for men aged up to 65 years, and ≤4 drinks per week for men over 65 years; consumption for women is set at half of the amount defined for men. Individuals experiencing facial flushing after alcohol consumption are advised to limit their alcohol intake to half the amount consumed by those who do not experience flushing.Discussion and Conclusion: The focus for these patients should be on their environment, particularly when implementing a family-oriented approach. The decision to initiate drug treatment should be based on the symptoms of the patient, with follow-up evaluations performed at appropriate time points. The “FRAMES Motivational Enhancement Interview” and “Insight Enhancement Counseling” are recommended for an effective counseling of patients.

BackgroundThis study's objective was to demonstrate pharmacokinetic (PK) similarity and safety of denosumab biosimilar, CT-P41, and United States-licensed reference denosumab (US-denosumab) in healthy male Asian adults, considering also pharmacodynamic (PD) outcomes.Research design and methodsThis double-blind, two-arm, parallel-group, Phase 1 study randomized (1:1) healthy males to a single (60-mg) subcutaneous dose of CT-P41 or US-denosumab. Primary endpoints were area under the concentration - time curve (AUC) from time zero to infinity (AUC0-inf), AUC from time zero to the last quantifiable concentration (AUC0-last), and maximum serum concentration (Cmax). PK equivalence was determined if 90% confidence intervals (CIs) for ratios of geometric least-squares means (gLSMs) were within the predefined 80-125% equivalence margin. Secondary PK, PD, safety, and immunogenicity outcomes were also evaluated.ResultsOf 154 participants randomized (76 CT-P41; 78 US-denosumab), 151 received study drug (74 CT-P41; 77 US-denosumab). Primary and secondary PK results, PD results, safety, and immunogenicity were comparable between groups. Ninety percent CIs for ratios of gLSMs were within the predefined equivalence margin for AUC0-inf (100.4-114.7), AUC0-last (99.9-114.3), and Cmax (95.2-107.3).ConclusionsFollowing a single dose in healthy males, CT-P41 demonstrated PK equivalence with US-denosumab.Trial registrationClinicalTrials.gov: NCT06037395

Yoon Jung Cha, In Ae Chang, Eun-Heui Jin, Ji Hye Song, Jang Hee Hong, Jin-Gyu Jung and Jung Sunwoo. Biomolecules & Therapeutics 2024;32:146-53. https://doi.org/10.4062/biomolther.2023.116