Pharmacometabolomics uncovers key metabolic changes in the first-in-human study of β-lapachone derivative.

Introduction: WK0202, a β-lapachone derivative under clinical development, activates NAD(P)H quinone dehydrogenase 1 (NQO1), acting as a detoxifying and antioxidant agent. In this study, a metabolomics investigation of β-lapachone derivatives in humans is performed to characterize drug-induced alterations in endogenous metabolic pathways.

Objectives: This study investigated metabolic alterations induced by WK0202 administration and their potential association with its therapeutic mechanism and efficacy.

Deciphering dynamic antibiotics-microbiome-metabolome interactions in preterm infants using systems biology.

Preterm infants are frequently administered antibiotics to prevent infections, yet their impact on the developing gut microbiota and metabolome remains complex and clinically significant. To systematically assess these effects, we analyzed longitudinal stool samples from 54 extremely- and very-low-birthweight infants by integrating clinical data, 16S rRNA-based microbiome profiling, targeted metabolomics, and community-scale metabolic modeling. Antibiotic exposure disrupted microbial diversity, depleted beneficial taxa, and altered metabolites such as short-chain fatty acids (SCFAs) and bile acids.

Quantitation of methotrexate polyglutamates in red blood cells and application in patients with Crohn's disease.

Methotrexate (MTX), a folate antagonist, is commonly administered at low doses for the treatment of Crohn's disease (CD). Anti-inflammatory effects of MTX are facilitated by its intracellular conversion to MTX polyglutamates (MTX-PGs). Because plasma-based monitoring of therapeutic response does not accurately reflect the therapeutic efficacy of MTX, quantifying intracellular MTX-PGs, potential biomarkers of the MTX response, is crucial.

Introducing Korea metabolomics data repository (KMAP): bridging Korean metabolomics data to global data sharing infrastructure.

The Korea MetAbolomics data rePository (KMAP), available at https://kbds.re.kr/KMAP , is a public repository for metabolomics datasets developed as a part of the Korea BioData Station (K-BDS).

Integrated genomics and metabolomics to identify cause-specific biomarkers for chronic kidney disease in a Korean population.

Background: The heterogeneity of chronic kidney disease (CKD) and fragmented analysis methods hinder the precise identification of novel biomarkers. We addressed this challenge using two independent cohorts to integrate genomics and metabolomics, aiming to identify cause-specific biomarkers for CKD in the Korean population.

Methods: A longitudinal genome-wide association study using the Cox proportional hazards model was conducted using the Ansan and Ansung cohort.

Saliva-based lacosamide monitoring paves the way toward personalized epilepsy pharmacotherapy.

Saliva, known for better patient compliance and simpler collection, is ideal for monitoring antiseizure medication (ASM) levels. This study aimed to validate saliva for measuring lacosamide, develop a pharmacokinetic (PK) model, and determine the optimal saliva concentration for seizure control in epilepsy patients. In our prospective study at Seoul National University Hospital from August 2021 to November 2022, we enrolled lacosamide-prescribed epilepsy patients, collecting their saliva and blood samples.

Safety, Tolerability, and Pharmacokinetics of Single and Multiple Topical Applications of Sodium Taurodeoxycholate, a Treatment for Atopic Dermatitis.

Sodium taurodeoxycholate (TDCA) gel is a novel candidate for the treatment of atopic dermatitis and is currently under clinical development. TDCA is a taurine-conjugated bile acid derivative that acts as a G protein-coupled bile acid receptor agonist and modulates immune responses. This phase 1 study aimed to investigate the safety, tolerability, and pharmacokinetic profile of sodium TDCA after single and multiple topical administrations of sodium TDCA gel in healthy male subjects.

Accurate Determination of Circulatory Lipids Using a Combination of HILIC-MRM and RPLC-PRM.

Circulatory lipids are important markers for characterizing disease phenotypes; however, accurately determining lipid species remains a significant challenge in lipidomic analysis. Here, we present a novel analytical workflow for accurate lipidome characterization in human plasma using mass spectrometry (MS) through the integration of hydrophilic interaction liquid chromatography (HILIC) and reversed-phase liquid chromatography (RPLC). This workflow enables rapid screening of 1,966 lipid species across 18 lipid classes using HILIC-multiple reaction monitoring (MRM), which enables facile identification of lipid species by lipid class-based separations.

A parallel reaction monitoring-mass spectrometric method for studying lipid biosynthesis in vitro using C-palmitate as an isotope tracer.

Background: Palmitate, which is the end product of fatty acid synthase, is the key fatty acid for understanding of lipid biosynthetic process in mammalian cells. Mass spectrometry (MS) methodology using C-palmitate can trace the lipid biosynthesis such as glycerolipids, glycerophospholipids, and sphingolipids. However, due to the interferences of natural heavy isotopes, accurate measurement of C-labeled lipid species has been limited.

Clinical development of oral semaglutide for the treatment of type 2 diabetes mellitus: focusing on early phase clinical trials.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder often associated with obesity and elevated cardiovascular risks. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become integral to T2DM management due to their clinical benefits of glucose regulation and weight loss. However, their subcutaneous administration presents challenges to patient adherence, limiting their widespread use.

Pharmacokinetics of post-transplant cyclophosphamide and its associations with clinical outcomes in pediatric haploidentical hematopoietic stem cell transplantation.

Background: Post-transplantation cyclophosphamide (PTCy) has paved the way for the increased use of alternative donors, including haploidentical familial donors, with acceptable engraftment and graft-versus-host disease (GVHD) rates. However, pharmacokinetic studies of PTCy in the pediatric population following myeloablative conditioning regimens are scarce.

Methods: We conducted a prospective and comprehensive pharmacokinetic analysis of pre- and post-transplantation cyclophosphamide levels in pediatric patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) using a myeloablative busulfan-based conditioning regimen.

Clustering-Based Identification of BMI-Associated Metabolites with Mechanistic Insights from Network Analysis in Korean Men.

Background: Epidemiological studies using metabolomics often encounter challenges due to metabolite profiles being influenced by multiple modifiable behavioral factors, including regular exercise, smoking, drinking, and weight control. This study aimed to identify modifiable behavioral factors reflected in metabolites by clustering subjects based on their metabolite profiles. Networks of metabolites were constructed to visualize their relationships and the differences between clustering groups.

Modulating the PD-1-FABP5 axis in ILC2s to regulate adipose tissue metabolism in obesity.

Obesity is closely linked to metabolic dysregulation and chronic inflammation, which significantly impact immune cell functions in adipose tissue. Type 2 innate lymphoid cells (ILC2s) have emerged as key regulators of energy homeostasis, positioning them as promising targets for obesity management. However, the mechanisms governing ILC2 activity and their therapeutic potential in obesity are not fully understood.

Nasal symbiont Staphylococcus epidermidis restricts influenza A virus replication via the creation of a polyamine-deficient cellular environment.

Studies on the immune-regulatory roles played by the commensal microbes residing in the nasal mucosa consider the contribution of antiviral immune responses. Here, we sought to identify the nasal microbiome, Staphylococcus epidermidis-regulated antiviral immune responses and the alteration of polyamine metabolites in nasal epithelium. We found that polyamines were required for the life cycle of influenza A virus (IAV) and depletion of polyamines disturbed IAV replication in normal human nasal epithelial (NHNE) cells.

Metabolic profiling of psoriasis vulgaris and palmoplantar pustulosis.

Psoriasis is a chronic inflammatory skin disorder with various subtypes, including psoriasis vulgaris (PV) and palmoplantar pustulosis (PPP). Metabolomics studies have provided insights into psoriasis pathogenesis. However, research on metabolomic alterations in PV and PPP patients is limited.

Inhibition of BCAT1-mediated cytosolic leucine metabolism regulates Th17 responses via the mTORC1-HIF1α pathway.

Branched-chain amino acids (BCAAs), particularly leucine, are indispensable AAs for immune regulation through metabolic rewiring. However, the molecular mechanism underlying this phenomenon remains unclear. Our investigation revealed that T-cell receptor (TCR)-activated human CD4 T cells increase the expression of BCAT1, a cytosolic enzyme responsible for BCAA catabolism, and SLC7A5, a major BCAA transporter.

Pharmacokinetic Interactions Between the Fixed-Dose Combination of Ezetimibe/Rosuvastatin 10/20 Mg and the Fixed-Dose Combination of Telmisartan/Amlodipine 80/5 Mg in Healthy Subjects.

Background: Management of hypertension and hyperlipidemia, which are common comorbid risk factors for cardiovascular diseases, require multiple medications. The development of a fixed-dose combination (FDC) containing ezetimibe, rosuvastatin, telmisartan, and amlodipine aims to enhance patient adherence and persistence, but the potential interactions among the four medications have not been studied. This study aimed to evaluate the pharmacokinetic (PK) interactions between the FDC of ezetimibe/rosuvastatin 10/20 mg (ER) and the FDC of telmisartan/amlodipine 80/5 mg (TA).

Comprehensive Evaluation of OATP- and BCRP-Mediated Drug-Drug Interactions of Methotrexate Using Physiologically-Based Pharmacokinetic Modeling.

Methotrexate (MTX) is an antifolate agent widely used for treating conditions such as rheumatoid arthritis and hematologic cancer. This study aimed to quantitatively interpret the drug-drug interactions (DDIs) of MTX mediated by drug transporters using physiologically-based pharmacokinetic (PBPK) modeling. An open-label, randomized, 4-treatment, 6-sequence, 4-period crossover study was conducted to investigate the effects of rifampicin (RFP), an inhibitor of organic anionic transporting peptides (OATP) 1B1/3, and febuxostat (FBX), an inhibitor of breast cancer resistance protein (BCRP), on the pharmacokinetics of MTX in healthy volunteers.

Pioglitazone-induced alterations of purine metabolism in healthy male subjects.

Pioglitazone is class of thiazolidinediones that activates peroxisome proliferator-activated receptors (PPARs) in adipocytes to improve glucose metabolism and insulin sensitivity and has been used as a treatment for type 2 diabetes. However, the underlying mechanisms of associated pioglitazone-induced effects remain unclear. Our study aimed to investigate endogenous metabolite alterations associated with pioglitazone administration in healthy male subjects using an untargeted metabolomics approach.

Pharmacokinetic interactions between fexuprazan, a potassium-competitive acid blocker, and nonsteroidal anti-inflammatory drugs in healthy males.

Fexuprazan, a novel potassium-competitive acid blocker, is expected to be used for the prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) induced ulcer. This study aimed to evaluate pharmacokinetic (PK) interactions between fexuprazan and NSAIDs in healthy subjects. A randomized, open-label, multicenter, six-sequence, one-way crossover study was conducted in healthy male subjects.

Effects of meal type on the bioavailability of vutiglabridin, a novel anti-obesity agent, in healthy subjects.

Vutiglabridin, which affects the pharmacokinetics (PKs) of food, is currently under clinical development for the treatment of obesity. This study aimed to evaluate the effects of low- and high-fat meals on PKs of vutiglabridin in healthy male subjects. A randomized, open-label, single-dose, three-period, six-sequence crossover study was conducted.