Clinical trials in South Korea are heavily concentrated in Seoul, limiting patient access in other regions. We conducted a cross-sectional ecological study of 17 Korean administrative divisions to assess regional infrastructure readiness for decentralized clinical trial (DCT) implementation, using data from the Health Insurance Review and Assessment Service (2024), the National Health Insurance Service (2024), and the Ministry of Food and Drug Safety (2024 to 2025). Provincial densities for four resource domains (specialists, nurses, beds, and medical equipment) were calculated per 100,000 patients and normalized to Seoul (= 1.00). Area-specific composite indices for four therapeutic areas were computed as the capped geometric mean of specialist and equipment densities, and an overall infrastructure index as the capped geometric mean of all four domain densities. Trial density was derived from 1,924 approved trials yielding 7,760 trial-center pairs (99% mapping rate). Among the 16 non-Seoul provinces, bed density was the most dispersed (coefficient of variation [CV] = 0.39, range 0.58 to 2.91), whereas specialist density was the most Seoul-concentrated of the four domains: no non-Seoul province reached 80% of Seoul's level (CV = 0.23, range 0.42 to 0.79). The four therapeutic-area composite indices showed comparable dispersion (CV 0.15 to 0.23; composite infrastructure CV 0.16; Pearson r = 0.72). Gwangju exhibited the largest gap between infrastructure capacity (index 0.94) and trial activity (density ratio 0.18). Clinical trial activity in Korea is disproportionately low relative to infrastructure, and regionspecific DCT strategies matched to local resource profiles can provide a practical framework for balanced trial participation.
Pharmacometrics has become a pivotal component of drug development and regulatory science in Korea, evolving from traditional pharmacokinetic (PK)/pharmacodynamic (PD) modeling to advanced approaches such as physiologically based pharmacokinetic (PBPK) modeling and quantitative systems pharmacology (QSP). This study reviews 192 pharmacometrics projects conducted between 2016 and 2024 by Korea's first pharmacometrics service company, covering diverse modalities, indications, and development stages. Key applications included first-in-human dose prediction, clinical trial design, and patient population-specific PK/PD modeling, with systematic tracking of regulatory outcomes and publications. While oncology remained the dominant therapeutic area, recent projects expanded into gene therapy, GLP-1 agonists, pediatric orphan indications, and advanced biologics including antibody-drug conjugates, bispecific antibodies, and engineered fusion proteins-using PBPK and semi-mechanistic models. These case-driven analyses highlight the growing regulatory impact and strategic value of pharmacometrics. As the field moves into a new era shaped by artificial intelligence/machine learning integration and Food and Drug Administration-driven new approach methodologies initiatives, this review not only reflects on past practices and achievements but also provides strategic perspectives to guide the future direction of pharmacometrics in Korea.
Low-dose combination therapies are recommended when monotherapy fails to control hypertension. This exploratory study aimed to compare the pharmacokinetics (PK) of 2 fixed-dose combinations (FDCs) of telmisartan, amlodipine, and chlorthalidone: half-dose test FDC (20/2.5/6.25 mg) and a conventional-dose reference FDC (40/5/12.5 mg). A randomized, open-label, single-dose, parallel-group study was conducted in healthy participants. Each participant received a single oral dose of either the test or reference FDC. Serial blood samples for telmisartan, amlodipine, and chlorthalidone were collected up to 72 hours post-dose, and PK parameters were calculated using noncompartmental analysis. The mean maximum plasma concentrations (Cmax) of telmisartan, amlodipine, and chlorthalidone were 41.34 and 155.75 μg/L, 1.74 and 4.42 μg/L, and 39.36 and 104.86 μg/L for the test and reference FDCs, respectively. The mean area under the concentration-time curves to the last measurable time point (AUClast) were 659.93 and 1,673.51 h·μg/L for telmisartan, 57.98 and 128.75 h·μg/L for amlodipine, and 831.73 and 1,826.86 h·μg/L for chlorthalidone. The test FDC demonstrated systemic exposure levels ranging from 0.27- to 0.39-fold for telmisartan, 0.39- to 0.44-fold for amlodipine, and 0.38- to 0.46-fold for chlorthalidone, compared to the reference FDC. In conclusion, the PK profiles of the half-dose test FDC were consistent with the known characteristics of the individual components. These provide the first PK data for this half-dose test FDC and may support its potential as an alternative treatment option for hypertension. However, as this was an exploratory study, the results should be interpreted with caution. Trial Registration:Clinical Research Information Service Identifier: KCT0010166.
Drug-drug interactions (DDIs) are a significant concern in clinical practice, DDIs might be relevant when drugs with pH-dependent solubility are co-administered with gastric acid-reducing agents (ARAs) such as histamine, H2-receptor antagonists and proton pump inhibitors. One class prone to such DDI at the absorption phase are the weakly basic protein kinase inhibitors (PKIs). The aim of this work is to review recent Food & Drug Administration (FDA) and European Medicines Agency (EMA) submissions for PKIs and evaluate the various approaches by drug developers to characterize pH-dependent DDI liability potentially affecting efficacy in this class of drugs and assess how this impacts the labelling. For this purpose, 32 FDA New Drug Applications (NDAs) and 25 EMA Market Authorization Applications of PKIs in the last 5 years (2019 through 2024) were reviewed More than two-thirds of the submissions included a dedicated clinical DDI studies with an ARA, which remains the most frequent approach to evaluating gastric pH-dependent DDIs among the PKIs investigated, albeit model-informed drug development approaches are also attempted by applicants in about 20% of the submissions. In cases where no clinical DDI study was submitted and alternative approaches taken, this was accepted by the approving agencies. Only the complete absence of data on the DDI potential triggered the request to provide the information post-marketing. A risk-based approach, considering the drug's properties and patient population, is crucial for determining the need for a clinical DDI study and should be discussed with the agencies during drug development.
Linezolid is an oxazolidinone antibiotic widely used to treat gram-positive infections and is associated with frequent adverse drug reactions (ADRs). Nevertheless, comprehensive evaluations of the incidence and risk factors of linezolid-related ADRs remain limited, with substantial variability across studies. This study aimed to evaluate the incidence of linezolid-associated ADRs and identify potential risk factors. A retrospective analysis was conducted using the Clinical Data Warehouse of Seoul National University Bundang Hospital (2003-2025). Among patients receiving at least one dose of linezolid, thrombocytopenia, neutropenia, anemia, leukopenia, and lactic acidosis were identified as ADRs. Kaplan-Meier analysis assessed cumulative incidence, and univariable and multivariable logistic regression were performed to identify risk factors. Among 1,198 patients, the cumulative incidences of thrombocytopenia, anemia, leukopenia, neutropenia, and lactic acidosis within three months after linezolid treatment initiation were 44.7%, 57.3%, 45.8%, 29.9%, and 27.5%, respectively. Concomitant use of trimethoprim-sulfamethoxazole was associated with anemia, while female sex and receipt of fresh frozen plasma transfusion were associated with lactic acidosis. Red blood cell transfusion was associated with an increased incidence of thrombocytopenia. This study demonstrated a higher incidence of linezolid-associated ADRs than previously reported in registration clinical trials. While several concomitant medications and clinical factors were identified as potential risk factors, associations involving transfusion-related variables should be interpreted cautiously, as they likely reflect underlying clinical vulnerability rather than a direct causal effect. These findings emphasize the importance of ADR monitoring during linezolid therapy and further research on the underlying mechanisms of linezolid-associated toxicity.
