This study investigated the usage patterns and impact of therapeutic drug monitoring (TDM) for risperidone and paliperidone in patients diagnosed with schizophrenia, utilizing retrospective ...real-world data sourced from a single center’s Clinical Data Warehouse. Our study cohort comprised patients diagnosed with schizophrenia undergoing treatment with either risperidone or paliperidone. Data on demographic characteristics, comorbidities, medication utilization, and clinical outcomes were collected. Patients were categorized into two groups: those undergoing TDM and those not undergoing TDM. Additionally, within the TDM group, patients were further stratified based on their risperidone and paliperidone concentrations relative to the reference range. The findings revealed that patients in the TDM group received higher risperidone and paliperidone doses (320 mg/day and 252 mg/day, p = 0.0045) compared to their non-TDM counterparts. Nevertheless, no significant disparities were observed in hospitalization rates, duration of hospital stays, or compliance between the two groups (p = 0.9082, 0.5861, 0.7516, respectively). Subgroup analysis within the TDM cohort exhibited no notable distinctions in clinical outcomes between patients with concentrations within or surpassing the reference range. Despite the possibility of a selection bias in assigning patients to the groups, this study provides a comprehensive analysis of TDM utilization and its ramifications on schizophrenia treatment outcomes.
Abstract
As a critical component of coherent X-ray diffraction imaging (CDI), phase retrieval has been extensively applied in X-ray structural science to recover the 3D morphological information ...inside measured particles. Despite meeting all the oversampling requirements of Sayre and Shannon, current phase retrieval approaches still have trouble achieving a unique inversion of experimental data in the presence of noise. Here, we propose to overcome this limitation by incorporating a 3D Machine Learning (ML) model combining (optional) supervised learning with transfer learning. The trained ML model can rapidly provide an immediate result with high accuracy which could benefit real-time experiments, and the predicted result can be further refined with transfer learning. More significantly, the proposed ML model can be used without any prior training to learn the missing phases of an image based on minimization of an appropriate ‘loss function’ alone. We demonstrate significantly improved performance with experimental Bragg CDI data over traditional iterative phase retrieval algorithms.
Overactive bladder (OAB) is characterized by urinary urgency and increased urinary frequency, substantially affecting quality of life. Tamsulosin and mirabegron combination therapy has been studied ...as a safe and effective treatment option for patients with OAB. This study evaluated the effects of combining these two drugs on their pharmacokinetics and safety profiles in healthy Korean males. In this open-label, fixed-sequence, three-period, drug–drug interaction phase 1 study, a total of 36 male participants were administered multiple doses of tamsulosin alone (0.2 mg once daily), mirabegron alone (50 mg once daily), or a combination of both drugs. The results showed that the combination of tamsulosin and mirabegron increased tamsulosin exposure in the plasma by approximately 40%. In contrast, the maximum plasma concentration of mirabegron was reduced by approximately 17% when administered with tamsulosin. No clinically significant changes in the safety profiles, vital signs, or clinical laboratory test results were observed in this study. In conclusion, there were no clinically relevant drug–drug interactions between tamsulosin and mirabegron in terms of pharmacokinetics, safety, and tolerability, suggesting that their combination could be a promising treatment option for patients with OAB.
Fexuprazan is a potassium-competitive acid blocker approved for treating gastric-acid-related diseases. Although the effectiveness of the recent formulation fexuprazan 10 mg has been demonstrated in ...Phase 3 clinical trials, data on the pharmacokinetics (PKs) of administering fexuprazan 10 mg twice daily at a 12 h interval are lacking. Moreover, it is imperative to ensure the bioequivalence of the new formulation with the previously approved 40 mg formulation. This study evaluated the pharmacokinetics (PKs) of the single- and multiple-dose oral administration of fexuprazan 10 mg tablets in healthy participants (Part 1) and investigated their bioequivalence with 40 mg tablets (Part 2). Part 1 comprised a single- and multiple-dose, one-sequence, two-period design and eight participants, while Part 2 comprised a single-dose, 2 × 2 crossover design and 24 participants. In Part 1, in Periods 1 and 2, participants received single and multiple doses (twice daily) of fexuprazan 10 mg, respectively. The maximum plasma concentration (Cmax) area under the concentration–time curve from 0 to 12 h (AUC0–12h) of the multiple-dose participants was approximately double that of the single-dose participants. In Part 2, the geometric mean ratios (90% confidence intervals) for Cmax and AUC from zero to the time of the last quantifiable concentration (AUClast) of the use of four fexuprazan 10 mg tablets to those of one fexuprazan 40 mg tablet were 1.0290 (0.9352–1.1321) and 1.0290 (0.9476–1.1174), respectively, meeting the bioequivalence criteria. Favorable PKs were observed after single and multiple administrations of one fexuprazan 10 mg tablet, and four fexuprazan 10 mg tablets were pharmacokinetically equivalent to one fexuprazan 40 mg tablet.
Although both diabetes mellitus (DM) and underweight are associated with increased risk of tuberculosis (TB), there are limited data evaluating TB risk while considering two factors ...simultaneously-body mass index (BMI) and DM. A retrospective cohort study was performed with 10,087,903 participants of the Korean National Health Screening Program in 2009. The cohort was followed up to the date of TB incidence, death, or until December 31, 2018. We compared the incidence and risk of TB according to BMI category and DM. During the 7.3-year follow-up duration, the incidence of TB was 0.92 per 1,000 person-years in the normal weight without DM, 2.26 in the normal weight with DM, 1.80 in the underweight without DM, and 5.35 in the underweight with DM. Compared to the normal weight without DM, the normal weight with DM, the underweight without DM, and the underweight with DM showed a 1.51-fold (95% CI, 1.46-1.57), a 2.21-fold (95% CI, 2.14-2.28), and a 3.24-fold (95% CI, 2.95-3.56) increased risk of TB, respectively. However, compared to the normal weight without DM, the severely obese without DM and those with DM showed a 0.37 (95% CI, 0.36-0.38) and a 0.42 (95% CI, 0.36-0.48)-fold decreased risk of TB, respectively. There was no significant joint effect of BMI and DM on the risk of incident TB in the overall population; a synergistic effect of underweight and DM was evident in participants <65 years of age, current smokers, and heavy drinkers. In conclusion, being underweight or DM individually increases the risk of incident TB. Based on our study results, a focused screening of incident TB in patients with DM may be beneficial.
Bersiporocin, a potent and selective prolyl‐tRNA synthetase inhibitor, is expected to show a synergistic effect with pirfenidone or nintedanib in patients with idiopathic pulmonary fibrosis. To ...validate the combination therapy of bersiporocin with pirfenidone or nintedanib, a randomized, open‐label, two‐part, one‐sequence, three‐period, three‐treatment study was designed to evaluate the effect of drug–drug interactions (DDI) regarding their pharmacokinetics, safety, and tolerability in healthy participants. In addition, the pharmacokinetic profiles of the newly formulated, enteric‐coated bersiporocin tablet were evaluated after single and multiple administrations. The potential effects of cytochrome P450 2D6 (CYP2D6) genotyping on bersiporocin pharmacokinetics and DDI were also explored. In Part 1, participants were sequentially administered a single dose of pirfenidone 600 mg, a single dose of bersiporocin 150 mg followed by multiple doses, and bersiporocin in combination with pirfenidone. In Part 2, participants were sequentially administered a single dose of nintedanib 150 mg, multiple doses of bersiporocin 150 mg, and bersiporocin in combination with nintedanib. Forty‐six participants completed the study. There was no significant pharmacokinetic DDI between bersiporocin, and pirfenidone or nintedanib. All adverse events (AEs) were mild to moderate and did not include serious AEs, suggesting bersiporocin alone or in combination therapy were well‐tolerated. The newly formulated bersiporocin 150 mg tablet showed a moderate accumulation index. There was no significant difference in the pharmacokinetic profiles after administration of bersiporocin alone or in combination therapy between CYP2D6 phenotypes. In conclusion, there are no significant DDI regarding the pharmacokinetics, safety, and tolerability of bersiporocin administration with pirfenidone or nintedanib.
A new sustained-release (SR) pregabalin tablet, YHD1119, was formulated for once-daily dosing. In the current study, we aimed to evaluate the pharmacokinetics of YHD1119 tablets in patients with ...reduced renal function. Subjects were grouped by creatinine clearance: > 60 mL/min/1.73m
(Cohort A) and 30-60 mL/min/1.73m
(Cohort B). Eight subjects in Cohort A received a YHD1119 75 mg tablet (Y75T) and a YHD1119 150 mg tablet (Y150T) in each period, and eight subjects in Cohort B received a Y75T. Non-compartment analysis and population pharmacokinetic analysis using a one-compartment model with first-order elimination and first-order absorption with lag time were performed. Sixteen subjects completed the study. The geometric mean ratio (GMR) (90% confidence intervals CI) for maximum concentration (C
), and area under the concentration-time profile from 0 to the last measurable time (AUC
) after Y75T of Cohort B to those of Y75T of Cohort A were 1.2273 (1.0245-1.4701), and 2.4146 (1.8142-3.2138), respectively. The GMR (90% CI) for C
, and AUC
after Y75T of Cohort B to those of Y150T of Cohort A were 0.6476 (0.5229-0.8021), and 1.1471 (0.8418-1.5632), respectively. Simulated steady-steady pregabalin concentrations after once-daily Y75T dosing in subjects with eGFR 45 mL/min/1.73 m
were within the range of steady-state concentrations simulated after once-daily Y150T dosing in subjects with eGFR 90 mL/min/1.73 m
. The total pregabalin exposure of Y75T in patients with moderate renal impairment was comparable with that of Y150T in subjects with near-normal renal function.
ClinicalTrials.gov Identifier: NCT05012436.
We developed a complex three-dimensional (3D) multilayer deposition method for the fabrication of single-walled carbon nanotubes (SWCNTs) using vacuum filtration and plasmonic carbonization without ...lithography and etching processes. Using this fabrication method, SWCNTs can be stacked to form complex 3D structures that have a large surface area relative to the unit volume compared to the single-plane structure of conventional SWCNTs. We characterized 3D multilayer SWCNT patterns using a surface optical profiler, Raman spectroscopy, sheet resistance, scanning electron microscopy, and contact angle measurements. Additionally, these carbon nanotube (CNT) patterns showed excellent mechanical stability even after elastic bending tests more than 1000 times at a radius of 2 mm.
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