Clinical Drug Investigation最新文献

{"title":"Economic Evaluation of Axicabtagene Ciloleucel as a Second-Line Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in South Korea: A Cost-Utility Analysis Based on the ZUMA-7 Trial.","authors":"Jiyeon Lee, Minsung Kim, Minseol Jang, Soomi Jo, Seulki Lee, Hae Sun Suh","doi":"10.1007/s40261-026-01557-9","DOIUrl":"https://doi.org/10.1007/s40261-026-01557-9","url":null,"abstract":"<p><strong>Background and objectives: </strong>Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in South Korea, with 30-40% of patients relapsing or becoming refractory after first-line therapy. Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy over standard-of-care (SoC) salvage chemotherapy plus autologous stem cell transplantation (ASCT) in the ZUMA-7 trial. While approved for second-line use in South Korea, its cost effectiveness has not yet been evaluated in the local healthcare setting. This study aimed to evaluate the cost effectiveness of axi-cel compared with SoC as a second-line treatment for adult patients with relapsed or refractory DLBCL eligible for ASCT from the perspective of the South Korean healthcare system.</p><p><strong>Methods: </strong>A partitioned survival model with a mixture cure approach was developed based on ZUMA-7 data to compare axi-cel with SoC as second-line treatment for transplant-eligible relapsed/refractory DLBCL. The analysis was conducted from the healthcare system perspective over a lifetime horizon, with costs and outcomes discounted at 4.5% annually. Utilities were estimated from EQ-5D-5L data in ZUMA-7 using the South Korean valuation set. Costs included treatment, subsequent therapies, resource use, adverse event management, and end-of-life care. Deterministic and probabilistic sensitivity analyses were conducted. Cost effectiveness was evaluated using a willingness-to-pay threshold of 1.5-2 times the gross domestic product per capita of South Korea.</p><p><strong>Results: </strong>Over a lifetime horizon, axi-cel yielded 8.68 life years (LYs) and 7.61 quality-adjusted life years (QALYs) versus 7.10 LYs and 5.91 QALYs for SoC. Total costs were higher for axi-cel, resulting in an incremental cost of KRW 93.9 million (US dollars (USD) 68,676). The incremental cost-effectiveness ratio (ICER) was KRW 55.5 million (USD 40,583) per QALY gained. Sensitivity analyses showed robust results, with subsequent therapy pattern as the most influential parameter.</p><p><strong>Conclusions: </strong>Axi-cel as second-line treatment for relapsed or refractory DLBCL provided meaningful gains in survival and quality-adjusted life and appeared to be a cost-effective alternative compared to SoC in South Korea.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of Nirmatrelvir/Ritonavir after Multiple Administration in a Phase 1, Open-Label Study in Healthy Chinese Adults and Compared with Non-Chinese Participants.","authors":"Nanyang Li, Jicheng Yu, Jufang Wu, Jing Zhang, Ying Ma, Chunye Zhang, Xiaoran Han, Jackie Gerhart, Shuangchen Cong","doi":"10.1007/s40261-026-01554-y","DOIUrl":"https://doi.org/10.1007/s40261-026-01554-y","url":null,"abstract":"<p><strong>Background and objectives: </strong>Nirmatrelvir (PF-07321332) has demonstrated antiviral activity and an acceptable safety profile in clinical studies. This study aimed to demonstrate the pharmacokinetic (PK) profiles of Chinese participants after administration of nirmatrelvir/ritonavir, and to further evaluate the ethnic differences between different races.</p><p><strong>Methods: </strong>This Phase 1, open-label, single-site study assessed the PK, safety, and tolerability of nirmatrelvir 300 mg plus ritonavir 100 mg administered twice daily for 10 days in healthy Chinese adults. In total, 14 Chinese participants were enrolled with an age range of 24 to 43 years. Samples were collected after first-dose administration on day 1 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 h after drug administration) and last-dose administration on day 10 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after drug administration) to assess PK parameters after a single dose and multiple doses; pre-dose samples were collected on days 5, 8, and 10 to confirm that steady-state was achieved. All PK samples were assayed with a liquid chromatography-tandem mass spectrometry method to quantify plasma concentration of nirmatrelvir and ritonavir. Study participants were monitored for safety for 28-35 days after the last-dose administration. Adverse events (AEs), clinical safety laboratory tests, vital signs, and 12-lead electrocardiograms were all monitored during study. Results for Chinese participants were compared with results in healthy non-Chinese adult participants who received the same nirmatrelvir/ritonavir dose in other Phase 1 studies.</p><p><strong>Results: </strong>All 14 healthy Chinese adults completed the study. Nirmatrelvir was rapidly absorbed, with a median t_max of approximately 2 h. Geometric mean nirmatrelvir C_max and AUC were 3.08 μg/mL and 19.66 μg·h/mL after the first dose and increased to 4.50 μg/mL and 32.01 μg·h/mL at steady state, with less than 2-fold accumulation and a mean terminal half-life of 6.84 h. Steady-state concentrations were achieved before day 5. Nirmatrelvir/ritonavir was well tolerated; 6 participants (42.9%) reported AEs, 4 of which (28.6%) were treatment-related mild dysgeusia. No serious AEs or discontinuations were reported. The results showed that the PK characteristics of nirmatrelvir/ritonavir in healthy Chinese adults were comparable with results from previous studies in non-Chinese healthy adults, with no apparent clinically significant differences observed between Chinese and non-Chinese participants.</p><p><strong>Conclusions: </strong>In healthy Chinese participants, the PK profile of nirmatrelvir 300 mg plus ritonavir 100 mg twice daily was comparable with that observed in non-Chinese participants, with an overall favorable safety profile, supporting the use of this dosing regimen for the Chinese population.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov id: </strong>NCT05339334.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost Effectiveness of Osimertinib with Chemotherapy Compared to Osimertinib Monotherapy and First-Generation EGFR-TKIs in Advanced NSCLC in the USA.","authors":"Mohammad Alnuman, Kangho Suh","doi":"10.1007/s40261-026-01535-1","DOIUrl":"10.1007/s40261-026-01535-1","url":null,"abstract":"<p><strong>Background and objectives: </strong>In clinical trials, osimertinib combined with chemotherapy has demonstrated improved efficacy in patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer. However, the projected long-term outcomes and the associated cost effectiveness compared to osimertinib monotherapy and first-generation EGFR-tyrosine kinase inhibitors remain uncertain.</p><p><strong>Methods: </strong>A lifetime partitioned survival model was developed from the US healthcare sector perspective using clinical trial data from pivotal trials FLAURA and FLAURA2. Model inputs included drug costs, administration costs, and health utilities sourced from the published literature. Dynamic drug pricing and a 3% discount rate were incorporated. Outcomes included life-years, quality-adjusted life-years (QALYs), total costs, and incremental cost-effectiveness ratios. One-way and probabilistic sensitivity analyses were performed.</p><p><strong>Results: </strong>Combination therapy yielded 2.96 QALYs at a cost of $692,796. The resultant incremental cost-effectiveness ratio was $265,601/QALY versus osimertinib monotherapy and $467,747/QALY versus first-generation EGFR-tyrosine kinase inhibitors. Findings were consistent across sensitivity analyses.</p><p><strong>Conclusions: </strong>While clinically effective, based on commonly accepted cost-effectiveness thresholds in the USA, our study suggests that osimertinib plus chemotherapy was not cost effective compared to osimertinib alone or first-generation EGFR-tyrosine kinase inhibitors.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"541-549"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147289159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determinants and Prognostic Impact of In-Hospital Sodium-Glucose Cotransporter-2 Inhibitor Initiation in Patients with Heart Failure.","authors":"Takuya Okamoto, Koichiro Matsumura, Shohei Hakozaki, Eijiro Yagi, Kazuyoshi Kakehi, Ayano Yoshida, Takayuki Kawamura, Kosuke Fujita, Masafumi Ueno, Kimiko Fujiwara, Manabu Takegami, Gaku Nakazawa","doi":"10.1007/s40261-026-01539-x","DOIUrl":"10.1007/s40261-026-01539-x","url":null,"abstract":"<p><strong>Background and objectives: </strong>Initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients hospitalised for heart failure (HF) is crucial for improving long-term outcomes. However, in real-world practice, a considerable proportion of patients are discharged without initiation. This study aimed to evaluate the initiation rate of SGLT2i, identify clinical factors associated with non-initiation, and examine the impact on long-term prognosis in patients hospitalised for HF.</p><p><strong>Methods: </strong>This single-centre, retrospective, observational analysis of a prospective registry included 781 consecutive patients who were hospitalised for HF between 2021 and 2024. The primary endpoint was the in-hospital initiation rate of SGLT2i. Secondary endpoints included clinical factors associated with non-initiation, assessed using multivariable logistic regression, and the incidence of the composite endpoint of all-cause mortality or HF rehospitalisation at 1 year according to SGLT2i prescription status at discharge, evaluated by log-rank test and Cox proportional hazards analysis.</p><p><strong>Results: </strong>A total of 467 patients (median age 81 [74-87] years, 50.3% male) were included in the final analysis. The initiation rate of SGLT2i during hospitalisation was 37.3% (174/467), and treatment discontinuation after initiation occurred in 8.6% (15/174). Multivariable analysis revealed that older age, non-diabetes, impaired renal function, higher left ventricular ejection fraction, malnutrition, impaired mobility, and cognitive dysfunction were independently associated with non-initiation. Among 346 patients with available follow-up data, the incidence of the composite endpoint at 1 year was significantly higher in the non-initiation group than in the initiation group (37.5% vs 21.3%, log-rank p = 0.001). In multivariable Cox analysis, not prescribed SGLT2i at discharge remained independently associated with worse long-term outcomes (hazard ratio 1.70, 95% confidence interval 1.07-2.69, p = 0.02).</p><p><strong>Conclusion: </strong>Both conventional clinical factors (e.g., diabetes, left ventricular ejection fraction) and aging-related factors (e.g., nutritional status, mobility, cognitive function) were independently associated with non-initiation of SGLT2i in hospitalised patients with HF. Importantly, non-initiation at discharge was significantly associated with worse long-term outcomes, underscoring the need to promote active initiation of SGLT2i in this population.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"489-499"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Ensitrelvir on the Pharmacokinetics of Combined Oral Contraceptives (Ethinyl Estradiol/Drospirenone) in Healthy Adult Women: A Phase 1 Fixed-Sequence, Multiple-Dose, Drug-Drug Interaction Study.","authors":"Ryosuke Shimizu, Risa Yokokawa Shibata, Ryuji Kubota, Sho Okuda, Takuhiro Sonoyama","doi":"10.1007/s40261-026-01541-3","DOIUrl":"10.1007/s40261-026-01541-3","url":null,"abstract":"<p><strong>Background and objective: </strong>Ensitrelvir has shown cytochrome P450 3A (CYP3A) inhibitory/induction potential in in vitro studies. This open-label, fixed-sequence Phase 1 study evaluated potential drug-drug interactions between ensitrelvir and a combined oral contraceptive (COC) containing ethinyl estradiol (EE) and drospirenone in healthy women of childbearing age.</p><p><strong>Methods: </strong>Healthy premenopausal women received EE/drospirenone (0.02 mg/3 mg) on days 1-24. Ensitrelvir was co-administered on day 20 (375 mg) and days 21-24 (125 mg/day). Blood samples were collected on days 19, 20, and 24 to assess plasma EE, drospirenone, and ensitrelvir concentrations. The primary endpoint was evaluation of the maximum plasma concentration, time to maximum plasma concentration, and area under the plasma concentration-time curve over the dosing interval τ (AUC_0-τ) assessed using noncompartmental methods. Treatment-emergent adverse events (TEAEs) were recorded for safety assessments.</p><p><strong>Results: </strong>The safety and pharmacokinetic parameter population comprised 24 and 23 participants, respectively. Compared with day 19, AUC_0-τ ratios on days 20 and 24 were 1.02- and 1.07-fold for EE and 1.10- and 1.80-fold for drospirenone, respectively. This result suggested the inhibitory potential for CYP3A to be likely weaker on the first day than on the last day. Ensitrelvir AUC_0-τ was higher on day 24 versus day 20 and comparable with that reported previously. Treatment-emergent adverse events occurred in 58.3% of participants, none of which were severe, serious, or led to treatment discontinuation.</p><p><strong>Conclusion: </strong>Ensitrelvir has no clinically meaningful effect on the pharmacokinetics of EE and drospirenone, and the combination was well tolerated. These findings support the co-administration of ensitrelvir with COCs in clinical practice.</p><p><strong>Trial registration: </strong>NCT06775730.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"561-570"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-Effectiveness Analysis of PI3K Inhibitors for Relapsed or Refractory Follicular Lymphoma in China: A Comparison Between Linperlisib and Duvelisib.","authors":"Xuefei Bai, Rongjie Shao, Xiaoning He","doi":"10.1007/s40261-026-01532-4","DOIUrl":"10.1007/s40261-026-01532-4","url":null,"abstract":"<p><strong>Background: </strong>Linperlisib, a highly selective PI3K-δ inhibitor, was firstly approved in China in November 2022 for the treatment of patients with relapsed or refractory follicular lymphoma (r/r FL) who had received at least two prior lines of systemic therapy (3L+ FL), demonstrating compelling clinical efficacy.</p><p><strong>Objective: </strong>This study aimed to evaluate the cost effectiveness of linperlisib compared to duvelisib for patients with 3L+ FL from the perspective of Chinese healthcare system.</p><p><strong>Methods: </strong>A lifetime three-state partitioned survival model was developed to integrate comparative efficacy and direct costs. An unanchored matching-adjusted indirect comparison (MAIC) was conducted using individual data from NCT04370405 and published aggregate data from the DYNAMO trial, aiming to derive comparative efficacy data and calculate patients' life-years gained. Utility values were from GADOLIN study, as neither trial collected them. Quality-adjusted life-years (QALYs) were calculated by multiplying life-years by utility values. Direct costs included costs of drug acquisition, adverse events, subsequent salvage therapy, health-care resource use (HCRU), and end-of-life care. A 5% annual discount rate was applied to both future QALYs and costs. The primary outcome was the incremental cost-effectiveness ratio (ICER), calculated as discounted incremental costs divided by incremental QALYs. The willingness-to-pay (WTP) threshold was set at China's 2023 per capita GDP (CNY89,358/QALY), with an ICER below this threshold indicating linperlisib was more cost effective. Model robustness was verified via one-way deterministic and probabilistic sensitivity analyses (DSA and PSA).</p><p><strong>Results: </strong>In the base-case analysis, linperlisib yielded an additional 1.58 QALYs (4.13 vs 2.55) at an incremental cost of CNY108,780 (CNY292,805 vs CNY184,025) compared with duvelisib. The resulting ICER was CNY68,996 per QALY, which was below the WTP. Although drug costs were the main cost driver, improved survival reduced end-of-life care costs by CNY1,507. Deterministic sensitivity analysis identified the price of linperlisib as the top influential parameter, yet all ICERs stayed below the WTP threshold. Probabilistic sensitivity analysis showed a 91.2% cost-effectiveness probability at the preset WTP, confirming robust findings.</p><p><strong>Conclusions: </strong>Linperlisib is cost effective compared to duvelisib for 3L+ FL patients in China, as verified in sensitivity analyses. Further study is warranted to confirm that it meets an unmet need in China.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"571-581"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Dexmedetomidine and Sufentanil in Preventing Adverse Reactions to Carboprost Tromethamine During Cesarean Section with Noninvasive Cardiac System Monitoring.","authors":"Jing Li, Bo Xiang, Xiaofeng Lei, Jin Yu","doi":"10.1007/s40261-026-01547-x","DOIUrl":"10.1007/s40261-026-01547-x","url":null,"abstract":"<p><strong>Background and objective: </strong>Carboprost tromethamine is commonly used to prevent or treat postpartum hemorrhage during cesarean section but causes frequent side effects. This study aimed to compare dexmedetomidine and sufentanil for preventing these side effects and assess hemodynamic stability.</p><p><strong>Methods: </strong>This is a single-center randomized controlled trial. Parturients undergoing elective cesarean section were randomized to Group D (dexmedetomidine intravenously), Group S (sufentanil intravenously), and Group C (saline intravenously). Carboprost tromethamine 250 µg was intrauterine injected after delivery. The incidence of complications, Ramsay sedation scores, and noninvasive cardiac system-derived hemodynamic parameters were analyzed. The primary endpoint is dexmedetomidine or sufentanil could relieve the nausea and vomiting caused by carboprost tromethamine.</p><p><strong>Results: </strong>A total of 152 subjects were included in the analysis. Both Groups D and S had significantly fewer intraoperative nausea and vomiting episodes (Group D 16% vs Group S 19.2% vs Group C 76%, P < 0.001) and higher Ramsay scores (P < 0.001) compared with Group C. Group C showed significant increases in mean arterial pressure and respiratory rate (P < 0.05). Heart rate in Group D was significantly lower than in Group C (P < 0.05). The total peripheral resistance was significantly lower in Group S at T2-T5 (from 2 minutes post-carboprost tromethamine until the end of surgery) and in Group D at T2-T4 (2, 5, and 10 minutes post-carboprost tromethamine) compared with Group C (P < 0.05). Cardiac output in Group S was higher at T2-T4 (2, 5, and 10 minutes post-carboprost tromethamine) than in Group C, and at T2-T3 (2 and 5 minutes post-carboprost tromethamine), it was even higher than in Group D (P < 0.05).</p><p><strong>Conclusions: </strong>Both dexmedetomidine and sufentanil alleviated carboprost tromethamine-induced side effects while maintaining stable hemodynamics. Sufentanil showed greater efficacy in reducing peripheral vascular resistance.</p><p><strong>Clinical trial registration: </strong>ChiCTR2000038350.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"551-559"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary MicroRNA Expression and Tacrolimus Pharmacokinetic Variability in Kidney Transplant Recipients: A Cross-sectional Study.","authors":"Nikola Stefanović, Katarina Danković, Radmila Veličković-Radovanović, Marija Vukelić-Nikolić, Maša Jović, Stevan Vujić, Vladana Stojiljković, Branka Mitić, Tatjana Cvetković","doi":"10.1007/s40261-026-01544-0","DOIUrl":"10.1007/s40261-026-01544-0","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of specific microRNAs and the intraindividual (IPV) and interindividual pharmacokinetic variability of tacrolimus (Tac) have been associated with unfavorable long-term outcomes after kidney transplantation. It remains unknown whether the effects of Tac pharmacokinetic variability are reflected in microRNA expression.</p><p><strong>Objective: </strong>The primary objective was to analyze the correlation between urinary microRNA (miR-21-5p, miR-142-3p, miR-155-5p, and miR-204-5p) relative expression levels in the long term and Tac pharmacokinetic variability parameters within the early period after kidney transplantation. Secondarily, correlation between urinary microRNA expression and long-term graft function were analyzed.</p><p><strong>Methods: </strong>In a cross-sectional study, the urinary microRNA expression levels were determined in 50 kidney transplant recipients in the long-term period after kidney transplantation and in 12 healthy controls. Patients were divided based on the Tac IPV and metabolic phenotype, defined by Tac dose-adjusted concentration (C₀/D) at the 3rd post-transplantation month.</p><p><strong>Results: </strong>Urinary expression of miR-142-3p (p = 0.022) and miR-204-5p (p = 0.007), but not miR-21-5p and miR-155-5p, differed significantly between patients in the long-term post-transplantation period and healthy controls. Patients characterized by fast/intermediate Tac metabolic phenotype had decreased urinary miR-204-5p expression compared to slow metabolizers (p = 0.007; p = 0.005, respectively). Patients with estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m² demonstrated significantly higher log-transformed expression of miR-204-5p compared to those with eGFR < 45 mL/min/1.73 m² (p = 0.003).</p><p><strong>Conclusion: </strong>This study indicated that the urinary expression levels of miR-142-3p and miR-204-5p were significantly different between kidney transplant recipients and healthy controls. Additionally, urinary miR-204-5p expression may be correlated with graft function in the long‑term post‑transplantation period, as well as with early Tac C₀/D values.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"517-530"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative Dosing Strategies to Enhance the Absorption of N-Acetyl-D-Mannosamine Monohydrate (ManNAc) in Healthy Adult Males.","authors":"Tahlia R Meola, Kellie La Fontaine, James Condon, Paul Wabnitz, Gianfranco Fornasini, Allan M Evans, Stephanie E Reuter","doi":"10.1007/s40261-026-01546-y","DOIUrl":"10.1007/s40261-026-01546-y","url":null,"abstract":"<p><strong>Background: </strong>GNE myopathy is a rare autosomal recessive muscle disease caused by biallelic mutations in GNE, a gene which encodes the bifunctional enzyme that catalyses the rate-limiting step of intracellular sialic acid biosynthesis. Whilst there is no current marketed therapy to treat the disease, current investigations focus on supplementation with N-acetyl-D-mannosamine monohydrate (ManNAc), a precursor in the biosynthesis of N-acetylneuraminic acid (Neu5Ac), the most abundant sialic acid. ManNAc possesses a low oral bioavailability, likely owing to poor absorption, and exhibits non-linearity across the therapeutic range, possibly due to saturation of intestinal transporter systems.</p><p><strong>Objectives: </strong>The study was conducted to examine if the absorption of ManNAc could be improved by administering a smaller (non-saturating) oral dose, more frequently, or by co-administering ManNAc with dietary salt, which might facilitate carrier-mediated transport.</p><p><strong>Methods: </strong>This was an open-label, randomised, cross-over study in 12 healthy male participants. Participants were administered 4 x 1 g doses of ManNAc every hour, 4 g ManNAc as a single dose with 1 g dietary salt or 4 g ManNAc alone.</p><p><strong>Results: </strong>The pharmacokinetic analysis population comprised 11 participants who received all three study treatments. Administration of ManNAc as split doses, more frequently, resulted in a 1.7-fold increase in ManNAc plasma exposure compared to a single 4 g dose, with a corresponding 1.9-fold increase in systemic Neu5Ac concentrations. In comparison, co-administration of ManNAc with dietary salt had no impact on ManNAc absorption.</p><p><strong>Conclusions: </strong>This study suggests that strategies to slow down the delivery of ManNAc to the small intestine may significantly improve its overall bioavailability and therefore reduce total daily dose requirements.</p><p><strong>Clinical trial registration: </strong>The clinical trial was registered on the Australian New Zealand Clinical Trials Registry (ID: ACTRN12620001127998).</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"531-540"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and Tolerability of Vortioxetine in Major Depressive Disorder: A Real-World Study in Switzerland.","authors":"Martin Kammerer, Gregor Hasler, Barbara Hochstrasser, Axel Baumann, Alexandra Sousek","doi":"10.1007/s40261-026-01537-z","DOIUrl":"10.1007/s40261-026-01537-z","url":null,"abstract":"<p><strong>Background and objectives: </strong>Vortioxetine is widely used in Switzerland for treating major depressive episodes, but systematically collected data from routine clinical practice are not available. We evaluated real-world effectiveness and tolerability of vortioxetine for treating major depressive episodes in Swiss clinical practice.</p><p><strong>Methods: </strong>A prospective non-interventional observational study was conducted with an observation period of approximately 8 weeks from vortioxetine initiation. Adults with a current major depressive episode for whom a decision to initiate vortioxetine had been made independent of the study were eligible for inclusion. Assessment of depressive symptoms, functioning, safety and tolerability were performed at four study visits. Pre-planned explorative descriptive statistics were applied.</p><p><strong>Results: </strong>Of 226 patients enrolled, 208 (92.0%) completed the study. At baseline, the mean (standard deviation) sum of the unanchored Montgomery-Åsberg Depression Rating Scale items was 34.3 (8.89), indicating severe depression. Depression severity tended to be underestimated when relying on clinical estimation without any scale alone. Significant reductions were observed from baseline to visit 4 in the sum of the unanchored Montgomery-Åsberg Depression Rating Scale items, in all individual items, and in the Clinical Global Impression-Severity scale (all p < 0.001). The severity of impairment of all assessed functioning domains also decreased. Adverse drug reactions were reported in 7.5% of patients. Effectiveness and tolerability of vortioxetine was rated good or very good by >88% of clinicians and patients.</p><p><strong>Conclusions: </strong>Patients who initiated vortioxetine for treating a major depressive episode experienced improvements in depressive symptoms and functioning. Vortioxetine was well tolerated. Underestimation of depressive episode severity by clinicians reinforces the importance of using rating scales in clinical practice.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"501-516"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}