Alterations in Plasma Lipid Profile before and after Surgical Removal of Soft Tissue Sarcoma.

Soft tissue sarcoma (STS) is a relatively rare malignancy, accounting for about 1% of all adult cancers. It is known to have more than 70 subtypes. Its rarity, coupled with its various subtypes, makes early diagnosis challenging.

Comparative Pharmacokinetic Profiles of a Novel Low-Dose Micronized Formulation of Raloxifene 45 mg (AD-101) and the Conventional Raloxifene 60 mg in Healthy Subjects.

Raloxifene hydrochloride shows poor bioavailability (only 2%) when orally administered because of its poor aqueous solubility and its extensive first-pass metabolism. A new micronized formulation of raloxifene was developed to improve bioavailability via enhanced gastrointestinal absorption. The primary objective of this study was to evaluate the pharmacokinetic characteristics of a new micronized raloxifene formulation (AD-101) in comparison with the conventional raloxifene formulation.

Hemagglutination Assay via Optical Density Characterization in 3D Microtrap Chips.

Hemagglutination assay has been used for blood typing and detecting viruses, thus applicable for the diagnosis of infectious diseases, including COVID-19. Therefore, the development of microfluidic devices for fast detection of hemagglutination is on-demand for point-of-care diagnosis. Here, we present a way to detect hemagglutination in 3D microfluidic devices via optical absorbance (optical density, OD) characterization.

Fed and fasted bioequivalence assessment of two formulations of extended-release fixed-dose combination dapagliflozin/metformin (10/1,000 mg) tablets in healthy subjects.

Unlabelled: Two open-label, randomized, two-period crossover studies were conducted to investigate the pharmacokinetic (PK) properties, safety, and bioequivalence of the test formulation (KD4004), a new fixed-dose combination (FDC) formulation of dapagliflozin and metformin extended release (XR) tablets, relative to the reference formulation (10 mg dapagliflozin/1,000 mg metformin XR FDC tablet) in healthy subjects under fasting (Part A) and fed (Part B) conditions. After giving the dose, serial blood samples were collected for a period of 48 hours. Primary PK parameters (AUC and C) were used to assess bioequivalence between two dapagliflozin/metformin XR (10/1,000 mg) FDC formulations under fed and fasting conditions.

Metabolomic analysis of the inhibitory effect of phthalates and bisphenol A on the antioxidant activity of vitamin D in human samples using liquid chromatography-mass spectrometry.

Vitamin D is important because it has roles in maintaining musculoskeletal health, redox homeostasis, and the immune system; however, it is commonly dysregulated by endocrine disrupting chemicals, particularly phthalates and bisphenol A (BPA). Continuous exposure to phthalates and BPA may alter the endogenous metabolite profiles associated with vitamin D activity, although the specific metabolites are yet to be identified. In this study, we identified the endogenous metabolites altered by phthalates and BPA exposure through untargeted metabolic profiling and investigated the role of these metabolites in vitamin D activity.

"Click-to-Clear": A Strategy to Minimize Radioactivity from the Blood Pool Utilizing Staudinger Ligation.

The availability of several bioorthogonal reactions that can proceed selectively and efficiently under physiologically relevant conditions has garnered the interest of biochemists and organic chemists alike. Bioorthogonal cleavage reactions represent the latest innovation in click chemistry. Here, we employed the Staudinger ligation reaction to release radioactivity from immunoconjugates, improving target-to-background ratios.

Optimizing and determining the click chemistry mediated Cu-64 radiolabeling and physiochemical characteristics of trastuzumab conjugates.

Over the last decade, Cu-labeling of monoclonal antibody (mAb) via inverse electron demand Diels-Alder click chemistry (IEDDA) have received much attention. Despite the tetrazine-transcyclooctene (Tz-TCO) click chemistry's convenience and efficiency in mAb labeling, there is limited information about the ideal parameters in the development of click chemistry mediated (radio)immunoconjugates. This encourages us to conduct a systematic optimization while concurrently determining the physiochemical characteristics of the model mAb, trastuzumab, and TCO conjugates.

A randomized, open-label, single-dose, two-way crossover study to assess the pharmacokinetics between two tablets of fixed-dose combination formulation with raloxifene and cholecalciferol and concomitant administration of each agents in healthy male volunteers.

Unlabelled: A new fixed-dose combination (FDC) formulation of raloxifene 60 mg and cholecalciferol 800 IU was developed to improve the medication compliance and overall efficacy of raloxifene treatment in postmenopausal osteoporosis patients. The aim of this study was to compare the pharmacokinetics between two tablets of FDC formulation of raloxifene/cholecalciferol and the two products administered concomitantly at respective doses. This randomized, open-label, single-dose, two-treatment, two-way crossover study included 46 volunteers.

Prothionamide Dose Optimization Using Population Pharmacokinetics for Multidrug-Resistant Tuberculosis Patients.

Prothionamide, a second-line drug for multidrug-resistant tuberculosis (MDR-TB), has been in use for a few decades. However, its pharmacokinetic (PK) profile remains unclear. This study aimed to develop a population PK model for prothionamide and then apply the model to determine the optimal dosing regimen for MDR-TB patients.

Lessons from a multicenter clinical trial with an approved wearable electrocardiogram: issues and practical considerations.

Unlabelled: Although wearable electrocardiograms (ECGs) are being increasingly applied in clinical settings, validation methods have not been standardized. As an exploratory evaluation, we performed a multicenter clinical trial implementing an approved wearable patch ECG. Healthy male adults were enrolled in 2 study centers.

Pharmacokinetics and Pharmacodynamics of YYD601, a Dual Delayed-Release Formulation of Esomeprazole, Following Single and Multiple Doses in Healthy Adult Volunteers Under Fasting and Fed Conditions.

Background: YYD601 was developed as a novel dual delayed release (DDR) formulation of esomeprazole to prolong the plasma esomeprazole concentration and extend the duration of acid suppression.

Purpose: The pharmacokinetic (PK) and pharmacodynamics (PD) characteristics of YYD601 after single and multiple oral administrations were investigated in healthy Korean adults under fasting and fed conditions, and compared with the original esomeprazole capsule.

Methods: In the single-center, randomized, open-label, parallel-design, two-period study, thirty two volunteers were enrolled into four dosing groups, including esomeprazole 40-mg (group A), YYD60130-mg (group B), YYD601 40-mg (group C), and YYD601 60-mg (group D) once daily for 5 days.

Pharmacokinetics of alectinib and its metabolite M4 in a patient with advanced lung adenocarcinoma undergoing hemodialysis: A case report.

This study presents the first detailed pharmacokinetic data of alectinib and its metabolite M4 in a patient with anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma undergoing hemodialysis. When the patient was administered a daily 300 mg bid dose of alectinib, the maximal observed plasma concentration (C ) of alectinib and M4 were 638 and 82 ng/ml, respectively, at steady-state (day 9). These pharmacokinetic data were similar to those previously reported in patients with normal organ function.

Effect of Low-Dose Persistent Organic Pollutants on Mitochondrial Function: Human and in Vitro Evidence.

Background: Chronic exposure to low-dose persistent organic pollutants (POPs) can induce mitochondrial dysfunction. This study evaluated the association between serum POP concentrations and oxygen consumption rate (OCR) as a marker of mitochondrial function in humans and in vitro cells.

Methods: Serum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in 323 adults.

Pharmacokinetic Drug Interaction Between Raloxifene and Cholecalciferol in Healthy Volunteers.

Osteoporosis is a common skeletal disorder, often leading to fragility fracture. Combination therapy with raloxifene, a selective estrogen receptor modulator, and cholecalciferol (vitamin D ) has been proposed to improve the overall efficacy and increase compliance of raloxifene therapy for postmenopausal osteoporosis. To our knowledge, there has been no report of any study on the pharmacokinetic interaction between raloxifene and cholecalciferol.

The possibility of low isomerization of β-lapachone in the human body.

β-Lapachone has been reported to have anticancer and various other therapeutic effects, but is limited in clinical applications by its low bioavailability. pH-Dependent isomerization can be suggested as one plausible factor influencing its low bioavailability. Since it is known that β-lapachone is converted to its isomer, α-lapachone in hydrochloric acid (HCl) solution, isomerization in the human body may be driven by HCl in the gastric fluid.

Effects of Orlistat/Phentermine versus Phentermine on Vascular Endothelial Cell Function in Obese and Overweight Adults: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Background: In clinical practice, concomitant treatment of orlistat with phentermine is commonly used off-label. However, clinical trials have not been performed to evaluate whether their combination improves metabolic parameters and cardiovascular risk factors other than weight loss. Therefore, we aimed to compare the efficacy of concomitant administration of orlistat and phentermine versus phentermine alone on the endothelial cell function in overweight and obese adults with back pain.

Rapid Interference-free Analysis of β-Lapachone in Clinical Samples Using Liquid Chromatography-Mass Spectrometry for a Pharmacokinetic Study in Humans.

A rapid analytical method developed for the analysis of β-lapachone in in vitro samples could not be directly applied to the analysis of clinical samples because of interference from unknown substances. Here, we developed and validated a rapid interference-free analytical method to accurately determine β-lapachone levels in human plasma using liquid chromatography-tandem mass spectrometry. First, we achieved the baseline-separation of β-lapachone from any interfering substances within a total run time of 4 min by adjusting the eluent strength of the mobile phase.

Evaluation of the Pharmacokinetic Drug-Drug Interaction between Micronized Fenofibrate and Pitavastatin in Healthy Volunteers.

Dyslipidemia is a major risk factor for development of atherosclerosis and cardiovascular disease (CVD). Effective lipid-lowering therapies has led to CVD risk reduction. This study evaluated the possible pharmacokinetic interactions between fenofibrate, a peroxisome proliferators-activated receptors α agonist, and pitavastatin, a 3-hydoxy-3-methylglutaryl-coenzyme A reductase inhibitor, in healthy Korean subjects.

Pharmacokinetics and bioequivalence of fixed-dose combination of candesartan cilexetil/amlodipine besylate (16/10 mg) versus coadministration of individual formulations in healthy subjects.

Unlabelled: This study compared the pharmacokinetics of a fixed-dose combination (FDC) of candesartan (16 mg) and amlodipine (10 mg) versus coadministration of individual formulations to clarify the bioequivalence of the FDC. In this randomized, open-label, single-dose, 2-treatment, 2-way crossover study, healthy Korean volunteers received a single dose of candesartan (16 mg) with amlodipine (10 mg) as either an FDC or single agents concomitantly administered, with a 2-week washout period. Serial blood samples were collected up to 72 hours after dosing for each treatment period, and plasma concentrations of candesartan and amlodipine were measured using a validated liquid chromatography-tandem mass spectrometry method.

A Pharmacokinetic Drug Interaction Between Fimasartan and Linagliptin in Healthy Volunteers.

Objective: Fimasartan, an angiotensin II type 1 receptor blocker, and linagliptin, a dipeptidyl-peptidase-4 inhibitor, are frequently coadministered to treat patients with hypertension and diabetes, respectively. This study sought to evaluate the pharmacokinetic interactions between fimasartan and linagliptin after co-administration in healthy Korean subjects.

Methods: The overall study was divided into two separate parts, with each part designed as an open-label, multiple-dose, two-period, and single-sequence study.

ICT-based adherence monitoring in kidney transplant recipients: a randomized controlled trial.

Background: Prior studies have explored the use of regular reminders to improve adherence among kidney transplant recipients (KTRs), but none have included real-time alarms about drug dosage, frequency, and interval. In the present study, we aimed to evaluate the efficacy and stability of an information and communication technology (ICT)-based centralized monitoring system for increasing medication adherence among Korean KTRs.

Methods: In this prospective, multicenter, randomized controlled study, enrolled KTRs were randomized to either the ICT-based centralized monitoring group or control group.

Tolerability and pharmacokinetics of ginsenosides Rb1, Rb2, Rc, Rd, and compound K after single or multiple administration of red ginseng extract in human beings.

Background: We investigated the tolerability and pharmacokinetic properties of various ginsenosides, including Rb1, Rb2, Rc, Rd, and compound K, after single or multiple administrations of red ginseng extract in human beings.

Methods: Red ginseng extract (dried ginseng > 60%) was administered once and repeatedly for 15 days to 15 healthy Korean people. After single and repeated administration of red ginsengextract, blood sample collection, measurement of blood pressure and body temperature, and routine laboratory test were conducted over 48-h test periods.

Understanding the pharmacokinetics of reversible metabolism.

This tutorial introduces the mathematical skills required to obtain exact and approximate solutions for reversible reactions and provides graphical insights to help understand the pharmacokinetics of reversible metabolism. The matrix method provides an easy way to derive the exact solution for the amount of each species as a function of time. The plots of the exact solutions reveal some characteristic features of the pharmacokinetic profiles of the reversible metabolism.

Pharmacokinetic and bioequivalence study between two formulations of S-1 in Korean gastric cancer patients.

Purpose: S-1 is an oral fluoropyrimidine anticancer drug consisting of the 5-fluorouracil prodrug tegafur combined with gimeracil and oteracil. The purpose of this study was to evaluate the pharmacokinetic (PK), bioequivalence, and safety of a newly developed generic formulation of S-1 compared with the branded reference formulation, in Korean gastric cancer patients.

Methods: This was a single-center, randomized, open-label, single-dose, two-treatment, two-way crossover study.