Assessing the Clinical Efficacy of Therapeutic Drug Monitoring for Risperidone and Paliperidone in Patients with Schizophrenia: Insights from a Clinical Data Warehouse.

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.

A randomized, double-blind, single-dose, phase 1 study comparing the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of denosumab biosimilar CT­P41 and reference denosumab in healthy males.

BACKGROUND: This study's objective was to demonstrate pharmacokinetic (PK) similarity and safety of denosumab biosimilar, CT­P41, and United States-licensed reference denosumab (US-denosumab) in healthy male Asian adults, considering also pharmacodynamic (PD) outcomes. RESEARCH DESIGN AND METHODS: This double-blind, two-arm, parallel-group, Phase 1 study randomized (1:1) healthy males to a single (60-mg) subcutaneous dose of CT­P41 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. RESULTS: Of 154 participants randomized (76 CT­P41; 78 US-denosumab), 151 received study drug (74 CT­P41; 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). CONCLUSIONS: Following a single dose in healthy males, CT­P41 demonstrated PK equivalence with US-denosumab. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06037395.

Pharmacokinetics and Food Effect Between a 100-mg Sustained-Release Tablet and a 50-mg Immediate-Release Tablet of Vildagliptin in Healthy Subjects.

Vildagliptin is one of the dipeptidyl peptidase-4 inhibitors. This study aimed to compare vildagliptin exposure between 50-mg immediate-release (IR) and 100-mg new sustained-release (SR) tablets, and evaluate the food effect on the pharmacokinetics (PKs) of vildagliptin. A randomized, open-label, 3-period, 3-treatment, 6-sequence crossover study was conducted on healthy subjects. During each period, subjects received the SR tablet either in the fasted (T1) or high-fat fed (T2) state once a day, or IR tablets administered twice a day in the fasted state (R). Blood samples for PK analysis were obtained serially up to 24 hours after dosing. Thirty-four subjects completed the study. The geometric mean ratios for the Cmax and AUC0-24h of T1 to R were 1.15 and 0.89, respectively. The corresponding values of T2 to T1 were 0.94 and 1.07, respectively. Vildagliptin exposure over 24 hours was similar between the SR and IR tablets. In addition, the PK profiles of the SR tablets were not altered by food. The SR tablets can be administered without a food effect and be an alternative option to IR tablets.

No drug-drug interactions between selective prolyl-tRNA synthetase inhibitor, bersiporocin, and pirfenidone or nintedanib in healthy participants.

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.

Drug-Drug Interactions between Tamsulosin and Mirabegron in Healthy Individuals Do Not Affect Pharmacokinetics and Hemodynamic Parameters Significantly.

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.

A Comparative Pharmacokinetic Study of Fexuprazan 10 mg: Demonstrating Bioequivalence with the Reference Formulation and Evaluating Steady State.

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.

Size-reduced fexuprazan 20 mg demonstrated the optimal bioavailability and bioequivalence with the reference formulation.

Fexuprazan (DWP14012), a potassium-competitive acid blocker, is a medical formulation prescribed to inhibit the secretion of gastric acid. The present study encompasses a comparative evaluation of pharmacokinetic (PK) analysis between the previous (reference) and size-reduced (test) formulation of fexuprazan 20 mg in healthy subjects. The study employed a randomized, open-label, single-dose, 2-sequence, 2-period, crossover design with a 7-day wash-out between periods. A total of 24 subjects were enrolled in this randomized study. During each period, the 21 subjects received either the test or reference formulation. Blood samples were collected at multiple time point ranging from 0 (pre-dose) to 48 hours post-dosing for PK analysis. The calculated PK parameters were considered bioequivalent when the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) were within the bioequivalence limit of 0.8-1.25. Safety and tolerability were included in the evaluation. A total of 20 subjects completed the study. Point estimates (90% CIs) of the GMRs were 1.1014 (0.9892-1.2265) for the maximum plasma concentration and 1.0530 (0.9611-1.1536) for the area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration, between the test and reference formulations. The reference and size-reduced test formulations of fexuprazan were well tolerated with no reports of serious adverse events. In conclusion, size-reduced and previous formulations of fexuprazan 20 mg were bioequivalent with regard to PKs, safety and tolerability.

Noni fruit extract ameliorates alcohol-induced hangover symptoms by reducing the concentrations of alcohol and acetaldehyde in a Sprague Dawley rat model and a human intervention study.

Various studies have reported that Noni shows various health effects. This study aimed to assess the ability of Noni fruit extract to serve as a single active functional ingredient for the alleviation of hangover symptoms in Sprague Dawley rats and healthy subjects in a single-dose, randomized, double-blind, crossover, placebo-controlled study. The rats were orally administered Noni fruit extract at 50 or 100 mg per kg body weight (B.W.) and HOVENIA. The blood ethanol (EtOH) and acetaldehyde concentrations were significantly lower in the 100 mg per kg B.W. group than in the EtOH group. Alcohol dehydrogenase and aldehyde dehydrogenase activity tended to increase in the 100 mg kg-1 B.W. group. In the human study, 30 subjects received either a placebo or Noni fruit extract (1 g). The Noni fruit extract group showed significantly faster time point at which the maximum concentration (Tmax) of alcohol than in the placebo group. In addition, blood acetaldehyde levels and diarrhea at 40 and 720 min after alcohol intake and the area under the curve between 40 and 60 min of acetaldehyde were significantly decreased in the Noni fruit extract group compared to the placebo group. According to the QUalitative INteraction Trees, subjects who were ≤36 years old who consumed more alcohol (>15 drinks per week) and had a higher total hangover score (>27.5 and 33) presented significantly lower blood acetaldehyde levels and less severe hangover symptoms. These results indicate that Noni fruit extract has the potential to improve hangover symptoms by decreasing alcohol and acetaldehyde levels.

Pharmacokinetic properties of a new sustained-release pregabalin tablet in subjects with reduced renal function.

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/1.73m2 (Cohort A) and 30-60 mL/min/1.73m2 (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 (Cmax), and area under the concentration-time profile from 0 to the last measurable time (AUClast) 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 Cmax, and AUClast 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 m2 were within the range of steady-state concentrations simulated after once-daily Y150T dosing in subjects with eGFR 90 mL/min/1.73 m2. 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. Trial Registration: ClinicalTrials.gov Identifier: NCT05012436.

Safety, Tolerability, and Serum/Tear Pharmacokinetics of Human Recombinant Epidermal Growth Factor Eyedrops in Healthy Subjects.

The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics (PKs) of rhEGF eyedrops after the administration of single and multiple doses in healthy subjects. A phase 1, randomized, double-blind, placebo-controlled, and single-ascending dose (SAD) and multiple-ascending dose (MAD) study were conducted in three dose groups (10, 50, and 100 µg/mL). The subjects randomly received rhEGF eyedrops or the placebo in a 3:1 ratio. Serial blood and tear samples for PK analysis were collected up to 36 h and 180 h post-dose in SAD and MAD studies, respectively. In addition, the serum and tear EGF concentrations were measured. Immunogenicity evaluations were conducted using serum anti-EGF antibody levels. A total of 50 subjects were enrolled and 48 subjects completed the study. Adverse drug reactions were mild and transient. There were no serious adverse events in this study. The tear EGF concentrations rapidly increased and returned to baseline after 4 h without any serum EGF level change after the administration of rhEGF eyedrops. rhEGF eyedrops were safe and well-tolerated in healthy subjects in a dose range of 10-100 µg/mL, indicating suitability for further studies in patients with corneal injury.