Cts-Clinical and Translational Science最新文献

{"title":"Elucidation of DPP-4 involvement in systemic distribution and renal reabsorption of linagliptin by PBPK modeling with a cluster Gauss–Newton method","authors":"Ryo Nakamura,&nbsp;Takashi Yoshikado,&nbsp;Yasunori Aoki,&nbsp;Yuichi Sugiyama,&nbsp;Koji Chiba","doi":"10.1111/cts.70047","DOIUrl":"10.1111/cts.70047","url":null,"abstract":"<p>The dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (LNG) exhibits target-mediated drug disposition (TMDD) in clinical settings, characterized by saturable binding to plasma soluble DPP-4 (sDPP-4) and tissue transmembrane DPP-4 (tDPP-4). Previous studies have indicated that saturable renal reabsorption of LNG contributes to its nonlinear urinary excretion observed in humans and wild-type mice, but not in Dpp-4 knockout mice. To elucidate the mechanisms underlying these complex phenomena, including DPP-4-related renal reabsorption of LNG, we employed physiologically-based pharmacokinetic (PBPK) modeling combined with a cluster Gauss–Newton method (CGNM). The CGNM facilitated the exploration of parameters in rat and human PBPK models for LNG and the determination of parameter identifiability. Through PBPK–CGNM analysis using reported autoradiography data ([¹⁴C]-LNG) in wild-type and Dpp-4-deficient rats, DPP-4-specific distributions of LNG in various tissues were clearly differentiated from nonspecific parts. By fitting to human plasma concentrations and urinary and fecal excretions of LNG after intravenous and oral administrations, multiple unknown PBPK parameters were simultaneously estimated by the CGNM. Notably, the amount of tDPP-4 and the reabsorption clearance for LNG–DPP-4 complexes were identifiable, indicating their critical role in explaining the complex nonlinear pharmacokinetics of LNG. Compared with previous PBPK analyses, the CGNM allowed us to incorporate greater model complexity (e.g., consideration of tDPP-4 expressions and in vitro binding kinetics), ultimately resulting in a more accurate reproduction of LNG's TMDD. In conclusion, by considering LNG as a high-affinity probe for DPP-4, comprehensive PBPK–CGNM analyses suggested a dynamic whole-body distribution of DPP-4, including its involvement in the renal reabsorption of LNG.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479821","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":"On placental and lactational transfer of IgG-based therapeutic proteins – Current understanding and knowledge gaps from a clinical pharmacology perspective","authors":"Daphne Guinn,&nbsp;Katherine Kratz,&nbsp;Kristie Baisden,&nbsp;Sarah Ridge,&nbsp;Sonaly McClymont,&nbsp;Elimika Pfuma Fletcher,&nbsp;Tamara Johnson,&nbsp;Yow-Ming Wang","doi":"10.1111/cts.70049","DOIUrl":"10.1111/cts.70049","url":null,"abstract":"<p>Maternal medication use may expose the developing fetus through placental transfer or the infant through lactational transfer. Because pregnant and lactating individuals have been historically excluded from early drug development trials, there is often limited to no human data available to inform pharmacokinetics (PK) and safety in these populations at the time of drug approval. We describe the known mechanisms of placental or lactational transfer of IgG-based therapeutic proteins and use clinical examples to highlight the potential for fetal or infant exposure during pregnancy and lactation. Placental transfer of IgG-based therapeutic proteins may result in systemic exposure to the developing fetus. A lactational transfer may be associated with local gastrointestinal (GI) exposure in the infant and may also result in systemic exposure, although data are very limited as proteins have shown instability in the GI tract. Understanding of PK and pharmacodynamic (PD) effects of IgG-based therapeutic proteins in infants exposed in utero as well as the potential exposure through human milk and its clinical implications is critical for developing treatment strategies for pregnant or lactating individuals. We share the current knowledge gaps and considerations for future evaluations to inform PK, PD, and the safety of IgG-based therapeutic proteins for safe use during pregnancy and lactation. With the increasing use of IgG-based therapeutic proteins in treating chronic diseases during pregnancy and lactation, there is a need to improve the quantity and quality of data to inform the safe use in pregnant and lactating individuals.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479822","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":"Correction to “Adult and pediatric relapsing multiple sclerosis phase II and phase III trial design and their primary endpoints: A systematic review”","authors":"","doi":"10.1111/cts.70052","DOIUrl":"10.1111/cts.70052","url":null,"abstract":"<p>Katsutoshi Hiramatsu, Hideki Maeda. Adult and pediatric relapsing multiple sclerosis phase II and phase III trial design and their primary end points: A systematic review. <i>Clin Transl Sci</i>. 2024;17:e13794.</p><p>We apologize for this error.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479820","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":"Pharmacokinetics, pharmacodynamics, and safety of izuforant, an H4R inhibitor, in healthy subjects: A phase I single and multiple ascending dose study","authors":"Byung Hak Jin,&nbsp;Taegon Hong,&nbsp;Byung Won Yoo,&nbsp;Choon Ok Kim,&nbsp;Dasohm Kim,&nbsp;Youn Nam Kim,&nbsp;Min Soo Park","doi":"10.1111/cts.70032","DOIUrl":"10.1111/cts.70032","url":null,"abstract":"<p>Izuforant is a selective, and potent histamine H4 receptor (H4R) antagonist developed to treat atopic dermatitis (AD). There is an unmet medical need for therapeutic agents to control inflammation and pruritus. Izuforant is a strong candidate for this task based on the findings of non-clinical studies showing that inhibition of the histamine-mediated signaling pathway via H4R by izuforant results in decreased pruritus and inflammation. This study aimed to evaluate the clinical pharmacokinetic (PK) and pharmacodynamic (PD) profiles of izuforant. Dose-block-randomized, double-blind, placebo-controlled, single- and multiple ascending dose studies were conducted in 64 healthy volunteers. For the single ascending dose (SAD) study, 10–600 mg izuforant was administered to the designated groups. For the multiple ascending dose (MAD) study, 100–400 mg izuforant was administered to three groups. The clinical pharmacokinetic (PK) profile of izuforant was evaluated using plasma and urine concentrations. Blood sampling for the PD assay, which measured imetit-induced eosinophil shape changes (ESC), was also conducted. A one-compartment PK model described the distribution and elimination profiles of izuforant. An imetit-induced ESC inhibition test was established and validated for PD evaluation as a measure of the H4R antagonistic effect. ESC inhibition was observed even at doses as low as 10 mg; however, this inhibition became stronger and lasted longer as the dose increased. All izuforant doses were well tolerated, and no discontinuations due to adverse events (AE) or deaths were reported.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479823","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":"Twenty-five years of addressing cutting-edge scientific, policy, and regulatory issues through collaboration: The Forum for Collaborative Research","authors":"Robin Schaefer,&nbsp;Alessi Ayvaz,&nbsp;Christopher R. Hoffman,&nbsp;Margot Yann,&nbsp;Zachary Rooney,&nbsp;Mitchell Leus,&nbsp;Shilpa Mitra,&nbsp;Veronica Miller,&nbsp;for the Forum for Collaborative Research","doi":"10.1111/cts.70051","DOIUrl":"10.1111/cts.70051","url":null,"abstract":"<p>Developing safe and effective drugs and other medical products is a complex and costly process. Drug development has been, historically, commonly competitive and uncollaborative, and this tendency toward a lack of interaction between stakeholders—the pharmaceutical industry, academia, regulatory agencies, healthcare providers, and communities, among others—can lead to missed opportunities to improve efficiency and, ultimately, public health. The Forum for Collaborative Research was established in 1997 to address current scientific, policy, and regulatory issues in global health through multistakeholder engagement and dialogue. By providing a neutral and safe space for discussion, the Forum's model has impacted how clinical trials in diverse health areas are conducted, supported broader and more equitable clinical trial participation, and accelerated delivery of new drugs. The Forum's focus and directions have shifted over time, and this responsiveness to the needs of the global health community will be critical to ensure that the Forum continues to support collaboration in global health. In this article, we present lessons learned from this innovative model of collaborative research and regulatory science, pioneered by the Forum for over 25 years, including the importance of collective ownership and governance by all stakeholders, and emphasis on common goals and advantages of collaboration.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479824","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":"A “one-step” approach to heart rate correction and statistical analysis applied to conscious dog QTc studies","authors":"Derek D. Best,&nbsp;Matthew M. Abernathy,&nbsp;Derek J. Leishman","doi":"10.1111/cts.70046","DOIUrl":"https://doi.org/10.1111/cts.70046","url":null,"abstract":"<p>A “one-step” method which combined the heart rate correction and statistical analysis for conscious nonhuman primate (NHP) QTc assessment was recently published. The principles of this method are applicable to other species. In the current analysis, we demonstrate the utility of the technique in conscious dog QTc studies. Two studies in male dogs (<i>n</i> = 8 and <i>n</i> = 7) implanted with telemetry devices were used. In both studies, treatments were randomized and all animals received all treatments. In the primary study, the effect on QTc of moxifloxacin was compared with vehicle. Each treatment (vehicle and moxifloxacin) was given on two separate occasions. In the second study, dogs were given vehicle or dofetilide. Conventional QTc analysis was compared with the “one-step” method. The effect on QTc relative to vehicle was determined along with the median minimal detectable difference. As expected, both moxifloxacin and dofetilide gave QTc increases with a maximum of ~ 20 ms. There was a significant increase in the sensitivity to detect a QTc effect when using the “one-step” method. The minimal detectable difference was 1.6 ms for the “one-step” method compared with 6.2 ms for the conventional method. These analyses are consistent with the increased sensitivity described for the “one-step” method applied to studies in NHP. The increased sensitivity should enhance the ability to support an integrated assessment of the QTc prolongation liability for new drugs.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435385","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":"Pharmacogenomic augmented machine learning in electronic health record alerts: A health system-wide usability survey of clinicians","authors":"Caroline W. Grant,&nbsp;Jean Marrero-Polanco,&nbsp;Jeremiah B. Joyce,&nbsp;Barbara Barry,&nbsp;Ashley Stillwell,&nbsp;Kellie Kruger,&nbsp;Therese Anderson,&nbsp;Heather Talley,&nbsp;Mary Hedges,&nbsp;Jose Valery,&nbsp;Richard White,&nbsp;Richard R. Sharp,&nbsp;Paul E. Croarkin,&nbsp;Liselotte N. Dyrbye,&nbsp;William V. Bobo,&nbsp;Arjun P. Athreya","doi":"10.1111/cts.70044","DOIUrl":"https://doi.org/10.1111/cts.70044","url":null,"abstract":"<p>Pharmacogenomic (PGx) biomarkers integrated using machine learning can be embedded within the electronic health record (EHR) to provide clinicians with individualized predictions of drug treatment outcomes. Currently, however, drug alerts in the EHR are largely generic (not patient-specific) and contribute to increased clinician stress and burnout. Improving the usability of PGx alerts is an urgent need. Therefore, this work aimed to identify principles for optimal PGx alert design through a health-system-wide, mixed-methods study. Clinicians representing multiple practices and care settings (<i>N</i> = 1062) in urban, rural, and underserved regions were invited to complete an electronic survey comparing the usability of three drug alerts for citalopram, as a case study. Alert 1 contained a generic warning of pharmacogenomic effects on citalopram metabolism. Alerts 2 and 3 provided patient-specific predictions of citalopram efficacy with varying depth of information. Primary outcomes included the System's Usability Scale score (0–100 points) of each alert, the perceived impact of each alert on stress and decision-making, and clinicians' suggestions for alert improvement. Secondary outcomes included the assessment of alert preference by clinician age, practice type, and geographic setting. Qualitative information was captured to provide context to quantitative information. The final cohort comprised 305 geographically and clinically diverse clinicians. A simplified, individualized alert (Alert 2) was perceived as beneficial for decision-making and stress compared with a more detailed version (Alert 3) and the generic alert (Alert 1) regardless of age, practice type, or geographic setting. Findings emphasize the need for clinician-guided design of PGx alerts in the era of digital medicine.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435369","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":"Hierarchical deep compartment modeling: A workflow to leverage machine learning and Bayesian inference for hierarchical pharmacometric modeling","authors":"Ahmed Elmokadem,&nbsp;Matthew Wiens,&nbsp;Timothy Knab,&nbsp;Kiersten Utsey,&nbsp;Samuel P. Callisto,&nbsp;Daniel Kirouac","doi":"10.1111/cts.70045","DOIUrl":"https://doi.org/10.1111/cts.70045","url":null,"abstract":"<p>Population pharmacokinetic (PK) modeling serves as the cornerstone for understanding drug behavior within a specific population. It integrates subject covariates to elucidate the variability in PK parameters, thus enhancing predictive accuracy. However, covariate modeling within this framework can be intricate and time-consuming due to the often obscure structural relationship between covariates and PK parameters. Previous attempts, such as deep compartment modeling (DCM), aimed to streamline this process using machine learning techniques. Nonetheless, DCM fell short in assessing residual errors and interindividual variability (IIV), potentially leading to model misspecification and overfitting. Furthermore, DCM lacked the ability to quantify model uncertainty. To address these limitations, we introduce hierarchical deep compartment modeling (HDCM) as an advancement of DCM. HDCM harnesses machine learning to discern the interplay between covariates and PK parameters while simultaneously evaluating diverse levels of random effects and quantifying uncertainty through Bayesian inference. This tutorial provides a comprehensive application of the HDCM workflow using open-source Julia tools.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435439","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":"Clinical significance and underlying mechanism of long non-coding RNA SNHG12 in lower extremity deep venous thrombosis","authors":"Shun Xiao,&nbsp;Chong Wang,&nbsp;Yongxin Li,&nbsp;Kun Zhang,&nbsp;Xuefei Jiao,&nbsp;Zonggang Zhao,&nbsp;Mingjin Guo,&nbsp;Bing Liu","doi":"10.1111/cts.70023","DOIUrl":"https://doi.org/10.1111/cts.70023","url":null,"abstract":"<p>D-dimer is widely used in the diagnosis of deep vein thrombosis (DVT), but the specificity is low. The study examined the diagnostic value of long non-coding RNA (lncRNA) SNHG12 in DVT, and preliminarily discussed its mechanism. SNHG12 levels were detected in 200 elderly fracture patients via RT-qPCR, including 38 DVTs. Logistic regression analysis and receiver operating characteristic (ROC) curve were applied for diagnostic value evaluation. HUVECs were used for function study. Cell proliferation, migration, apoptosis, release of inflammatory cytokines, and adhesion factors were detected. Student's <i>t</i> test and one-way ANOVA were applied for data comparison between two or among three or more groups. Correlation analysis of indicators was completed via Pearson's correlation analysis. Bioinformatics analysis predicted the target miRNAs and genes of SNHG12, with GO and KEGG for the function enrichment. It was found that SNHG12 was at low expression in DVT patients, and negatively correlated with D-dimer concentration (<i>r</i> = −0.535). SNHG12 and D-dimer were independent influence factors related to the development of DVT. SNHG12 and D-dimer combination had the best performance in DVT diagnosis. In HUVECs, SNHG12 promoted cell proliferation and migration and restricted the release of inflammatory cytokines and adhesion factors, but these influences were counteracted by miR-424-5p. A total of 208 overlapping target genes of miR-424-5p were identified, and their function was enriched in cellular cycle and senescence. PI3K-Akt signaling pathway was the most significant pathway based on KEGG results. In conclusion, SNHG12 had good diagnostic potential for DVT combined with D-dimer. SNHG12 maintains vascular endothelial cell function by acting as a competitive endogenous RNA (ceRNA) for miR-424-5p.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435629","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":"Preclinical metabolism and metabolic drug–drug interaction profile of pedunculoside and rotundic acid","authors":"Liang Wu,&nbsp;Linling Dong,&nbsp;Zhu Zhou,&nbsp;Xin Wang,&nbsp;Yujie Lin,&nbsp;Xuesong Shi,&nbsp;Peijing Wang,&nbsp;Suocheng Xu,&nbsp;Zhiyi Fang","doi":"10.1111/cts.70043","DOIUrl":"10.1111/cts.70043","url":null,"abstract":"<p>Pedunculoside and rotundic acid, the most abundant components in plants of the genus <i>Ilex</i> L. (Aquifoliaceae), exhibit biological and pharmacological significance in the treatment of cardiovascular diseases. However, there have been few studies on their metabolism. This study performed a systematic metabolism study of pedunculoside and rotundic acid and evaluated their potential for herb–drug interaction. Pedunculoside or rotundic acid was incubated with human liver microsomes and recombinant human metabolic enzymes, and analyzed using LC-Q-TOF/MS and LC–MS/MS. Pedunculoside was found to be the most stable in human liver microsomes, whereas rotundic acid was easily metabolized. Eight pedunculoside metabolites and six rotundic acid metabolites were detected and tentatively identified through hydroxylation, glucuronidation, acetylation, and glucose conjugation. Hydroxylation of pedunculoside is mainly catalyzed by CYP3A4/5 and partly by CYP2C8. Hydroxylation of rotundic acid is almost exclusively catalyzed by CYP3A4/5, and its glucuronidation reaction is mediated by UGT1A4. Neither pedunculoside nor rotundic acid showed CYP inhibition (IC₅₀ values &gt; 50 μM) with the probe substrates of major CYP isoforms during incubation with human liver microsomes. This study is the first investigation into the in vitro metabolism of pedunculoside and rotundic acid using human liver microsomes. It also aims to assess their potential as perpetrators of drug–drug interactions involving CYP enzymes. The comprehensive metabolism and drug interaction studies of pedunculoside and rotundic acid enable us to evaluate and manage potential risks with their use in pharmacotherapy.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401861","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}