Clinical therapeutics最新文献

{"title":"The Effect of Rituximab on the Cognitive Function of Patients with Relapsing-Remitting Multiple Sclerosis","authors":"Masood Najafi Msc ,&nbsp;Ghasem Farahmand MD ,&nbsp;Pargol Balali MD ,&nbsp;Atefeh Behkar MD, MPH ,&nbsp;Mojtaba Shahbazi MD ,&nbsp;Negar Moradian MD ,&nbsp;Sara Pouyanmanouchehri MD ,&nbsp;Mohammad Hossein Harirchian MD ,&nbsp;Sara Ranji MD","doi":"10.1016/j.clinthera.2024.07.011","DOIUrl":"10.1016/j.clinthera.2024.07.011","url":null,"abstract":"<div><h3>Purpose</h3><div>Cognitive impairment can begin in the early stages of multiple sclerosis (MS). No medicine has been approved for treating cognitive impairment in MS patients. There is a lack of data on the role of rituximab in managing cognitive impairment in MS patients. Using minimal assessment of cognitive function in MS (MACFIMS), this study aims to investigate the effect of rituximab on the cognitive status of relapsing-remitting MS (RRMS) patients.</div></div><div><h3>Methods</h3><div>In this pre-post interventional trial, 28 eligible RRMS patients participated. They were administered rituximab for a year. Cognitive tests (MACFIMS), MS neuropsychological questionnaire (MSNQ), and Beck depression inventory-fast screen (BDI-FS) scores were evaluated at baseline, six, and 12 months following rituximab administration.</div></div><div><h3>Findings</h3><div>Eighteen participants with a mean age of 40.5 ± 12.91, 7 men, completed all three follow-ups. There was no statistically significant change in BDI-FS, MSNQ, Paced Auditory Serial Addition Test (<em>P</em>: 0.743), Symbol Digit Modalities Test (<em>P</em>: 0.711), Brief Visual Memory Test (BVMT) (<em>P</em>: 0.426), learning BVMT (<em>P</em>: 0.268), and delayed recall BVMT (<em>P</em>: 0.394) scores. However, the California Verbal Learning Test (CVLT), CVLT learning, and Controlled Oral Word Association Test scores significantly improved by 45.2% (<em>P</em> &lt; 0.001), 12.3% (<em>P</em>: 0.013), and 26.7% (<em>P</em>: 0.011), respectively, 6-month follow-up rituximab treatment. There was a significant improvement in CVLT (+55.7%, <em>P</em> &lt; 0.001), CVLT learning (+15.9%, <em>P</em>: 0.011), and delayed recall CVLT (+28%, <em>P</em>: 0.022) scores 12-month follow-up rituximab treatment.</div></div><div><h3>Implications</h3><div>Rituximab prevents cognitive deterioration and improves some cognitive functions. Further investigations with a larger sample size, longer follow-ups, and inclusion of a placebo or another treatment arm are recommended.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dosing of Venetoclax in Pediatric Patients with Relapsed Acute Myeloid Leukemia: Analysis of Developmental Pharmacokinetics and Exposure-Response Relationships","authors":"Mohamed Badawi ,&nbsp;Sathej Gopalakrishnan ,&nbsp;Benjamin Engelhardt ,&nbsp;Tammy Palenski ,&nbsp;Seth E. Karol ,&nbsp;Jeffrey E. Rubnitz ,&nbsp;Rajeev Menon ,&nbsp;Ahmed Hamed Salem","doi":"10.1016/j.clinthera.2024.09.008","DOIUrl":"10.1016/j.clinthera.2024.09.008","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This work aimed to characterize the pharmacokinetics and exposure-response relationships of venetoclax in pediatric patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) to identify venetoclax doses to be administered to pediatric patients in the phase 3 study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Data from 121 patients across three phase 1 studies enrolling pediatric patients with R/R malignancies were utilized to develop a population pharmacokinetic model to describe venetoclax pharmacokinetics in pediatric patients. Individual patient average venetoclax plasma concentration up to the event of interest, derived based on the population pharmacokinetics analysis, was used to evaluate the exposure-response relationships to efficacy (complete response) and safety (neutropenia and thrombocytopenia) endpoints for patients with AML who received venetoclax in combination with azacitidine, decitabine, or cytarabine (n = 36). The population pharmacokinetic model was then used to simulate exposures in pediatric age- and weight-based subgroups to identify the venetoclax doses for pediatric patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;The pharmacokinetic data were adequately described by the two-compartment population pharmacokinetic model with first-order absorption and elimination. The model accounted for cytochrome P450 3A developmental changes using a maturation function and incorporated allometric scaling to account for growth and body size effect. Weight was identified as a statistically significant covariate on clearance and volume of distribution and retained in the final model. Population pharmacokinetic estimates were comparable to previously reported estimates in adults. Exposure-response analyses suggested that the clinical efficacy of venetoclax in combination with high-dose cytarabine (HDAC) is maximized at 600 mg adult-equivalent, and higher doses are unlikely to enhance clinical efficacy. Venetoclax 600 mg adult-equivalent was selected for further development in combination with HDAC. Additionally, venetoclax 400 mg adult-equivalent was selected for bridging/maintenance therapy in combination with azacitidine. Flat exposure-response relationships were observed with Grade ≥3 neutropenia and thrombocytopenia. Doses were selected based on weight (allometric scaling) for children aged ≥2 years old and based on weight and CYP3A ontogeny for children aged &lt;2 years. The selected age- and weight-based dosing scheme of venetoclax is projected to achieve venetoclax exposures in pediatric subgroups comparable to those observed in adults receiving venetoclax 400 mg or 600 mg.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Implications&lt;/h3&gt;&lt;div&gt;This work characterized the pharmacokinetics and exposure-response relationships of venetoclax in pediatric patients and guided the selection of pediatric dosing regimens in support of the venetoclax phase 3 trial in pediatric AML (NCT05183035).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Clinical Studies&lt;/h3&gt;&lt;div&gt;","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lessons Learned From Clinical Studies in Centronuclear Myopathies: The Patient Perspective—A Qualitative Study","authors":"","doi":"10.1016/j.clinthera.2024.03.008","DOIUrl":"10.1016/j.clinthera.2024.03.008","url":null,"abstract":"<div><h3>Background</h3><div>Since 2014, several clinical studies focusing on centronuclear myopathies have been conducted, including a prospective natural history study, a gene transfer clinical trial and a clinical trial using an antisense oligonucleotide. Dedicated patient organizations have played an important role in this process. The experience of members of these organizations, either as a study participant, parent or as a patient organization member communicating with the sponsors are potentially very informative for future trial design.</div></div><div><h3>Methods</h3><div>We investigated the burden of and the lessons learned from the first natural history studies and clinical trials from a patient perspective using a qualitative approach. We arranged 4 focus groups with a total of 37 participants from 3 large international patient organizations: ZNM-ZusammenStark!, the Myotubular Trust, and the MTM-CNM Family Connection. 4 themes, based on a systematic literature search were discussed: Expectations and preparation, Clinical study participation, Communication and Recommendations for future clinical trials. The focus group recordings were transcribed, anonymized, and uploaded to Atlas-ti version 8.1 software. The data were analyzed using a thematic content analysis.</div></div><div><h3>Results</h3><div>Overall, participants were realistic in their expectations, hoping for small improvements of function and quality of life. The realization that trial participation does not equate to a treatment was challenging. Participating in a clinical study had a huge impact on many aspects of daily life, both for patients and their immediate families. First-hand insights into the burden of the design and its possible effect on performance were provided, resulting in numerous compelling recommendations for future clinical studies. Furthermore, participants stressed the importance of clear communication, which was considered to be especially vital in cases of severe adverse events. Finally, while patients were understanding of the importance of adhering to the regulations of good clinical practice, they indicated that they would strongly appreciate a greater understanding and/or acknowledgment of the patient perspective and a reflection of this perspective in future clinical trial design.</div></div><div><h3>Conclusion</h3><div>The acknowledgment and inclusion of patients’ perspectives and efficient and effective communication is expected to improve patient recruitment and retention in future clinical studies, as well as more accurate assessment of the patient performance related to suitable planning of the study visits.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140763181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Balancing Evidence and Need: Variation in US Commercial Payer Coverage of Esketamine","authors":"Ekwu B. Ochigbo RPhPhD,&nbsp;Molly T. Beinfeld MPH,&nbsp;James D. Chambers MPharmPhD","doi":"10.1016/j.clinthera.2024.06.017","DOIUrl":"10.1016/j.clinthera.2024.06.017","url":null,"abstract":"<div><h3>Purpose</h3><div>Variations in US commercial health plan coverage policies affect how patients access medications. Plans may vary in treatment access criteria, line of therapy, and prescriber requirements. In this study, we examined coverage of esketamine hydrochloride (Spravato) for major depressive disorder (MDD) and treatment-resistant depression (TRD) to answer the following question: how do US commercial health plans cover esketamine, and how do they guide prompt patient access to the drug?</div></div><div><h3>Methods</h3><div>We used information from the Tufts Medical Center Specialty Drug Evidence and Coverage database, which includes coverage policies issued by 18 large commercial health plans in the United States. Esketamine coverage policies for MDD and TRD active in December 2022 were collated and analyzed. We compared coverage policies according to step therapy protocols, patient subgroup restrictions, and prescriber requirement criteria, evaluating patient access using the number of restrictions and proportion of plans including each criterion.</div></div><div><h3>Findings</h3><div>Plans more often imposed step therapy requirements for access to esketamine for TRD than for MDD, with line of treatment of ≤9 steps for MDD compared with 1 to 5 steps for TRD. Plans also varied with respect to the therapies they required patients to first try and experience treatment failure before granting access to esketamine for both indications. Clinical coverage requirements varied in thresholds and rating scales used to assess severity of depressive symptoms.</div></div><div><h3>Implications</h3><div>Plans vary in terms of line of therapy and clinical coverage requirements for access to esketamine. Variation in health plan coverage policies may result in inequitable access and added complexity for patients and clinicians navigating care, which may delay access to urgent treatment.</div></div><div><h3>ClinicalTrials.gov identifiers</h3><div>Not applicable.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination of High-Dose Daptomycin and Ceftriaxone for Cardiac Implantable Electronic Device Infections: A 10-Year Experience","authors":"Giacomo Ponta ,&nbsp;Martina Ranzenigo ,&nbsp;Alessandra Marzi ,&nbsp;Chiara Oltolini ,&nbsp;Chiara Tassan Din ,&nbsp;Caterina Uberti-Foppa ,&nbsp;Vincenzo Spagnuolo ,&nbsp;Patrizio Mazzone ,&nbsp;Paolo Della Bella ,&nbsp;Paolo Scarpellini ,&nbsp;Antonella Castagna ,&nbsp;Marco Ripa","doi":"10.1016/j.clinthera.2024.07.012","DOIUrl":"10.1016/j.clinthera.2024.07.012","url":null,"abstract":"<div><h3>Purpose</h3><div>Cardiac implantable electronic device (CIED) infections are increasingly common. Gram-positive bacteria such as coagulase negative staphylococci and <em>Staphylococcus aureus</em> are the most commonly involved pathogens. The aim of this study was to describe the characteristics and outcome of patients with CIED infections who underwent device removal and were empirically treated with high dose (8–12 mg/kg daily) daptomycin (DAP) in combination with ceftriaxone (CRO).</div></div><div><h3>Methods</h3><div>Retrospective, single center study including patients admitted at IRCCS San Raffaele Hospital (Milan, Italy), from June 2011 to June 2021, who underwent device removal for CIED infection and were empirically treated with DAP/CRO.</div></div><div><h3>Findings</h3><div>Overall, 147 patients were included in this study. Median duration of therapy was 16 days (IQR 14–26). Empirical treatment with DAP/CRO was confirmed as definitive treatment in 140 patients (95.2%). In 7 (4.8%) patients DAP/CRO were discontinued according to the definite microbiological isolates: Corynebacterium spp. (4), Pseudomonas aeruginosa (2), Enterobacter cloacae (1). Ten patients (6.8%) underwent treatment simplification to narrow-spectrum antibiotics. One patient (0.6%) interrupted DAP-CRO due to pancytopenia.</div><div>6-month follow-up was available for 123/147 patients (83.7%): 9 patients recurred with a CIED infection (7.3%), and 9 died (7.3%).</div></div><div><h3>Implications</h3><div>In our 10-year experience, high-dose DAP in combination with CRO represented a good option for empirical therapy of CIED infections. DAP-CRO combination was safe and effective, showing no significant drug-related adverse events and low rates of 6-month recurrence and mortality.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical Compatibility of Reduced Glutathione for Injection With 44 Intravenous Drugs During Simulated Y-site Administration","authors":"Rui Wu MS ,&nbsp;Gaochao Zhu BS ,&nbsp;Yinghui Ju MS ,&nbsp;Yue Zhu MS ,&nbsp;Menglin Wang MS ,&nbsp;Yangyu Zhao MS ,&nbsp;Sheng Liu BS","doi":"10.1016/j.clinthera.2024.08.002","DOIUrl":"10.1016/j.clinthera.2024.08.002","url":null,"abstract":"<div><h3>Purpose</h3><div>Reduced glutathione (GSH) is extensively used in clinical therapeutics due to its antioxidative and cytoprotective properties. It is essential in the management of various chronic and acute conditions and serves as an adjunct therapy in oncology. Despite its widespread use, the physical compatibility of GSH with other intravenous drugs during Y-site administration has not been thoroughly investigated, posing risks such as reduced efficacy and adverse reactions. This study fills this critical gap by examining the physical compatibility of GSH with 44 commonly used intravenous drugs in simulated Y-site administration with 0.9% sodium chloride injection (NS) and 5% dextrose injection, aiming to enhance patient safety and clinical outcomes.</div></div><div><h3>Methods</h3><div>Simulated Y-site administration was conducted <em>in vitro</em> by mixing 24 mg/mL of GSH with equal volumes of 44 diluted intravenous drugs. Physical compatibility was assessed by observing visual changes, checking for the Tyndall effect, measuring turbidity, and monitoring pH levels at 0, 0.5, 1, 2, and 4 hours post-mixing. Physical compatibility was defined as the absence of color changes, gas evolution, particulate formation, and the Tyndall effect within 4 hours, with turbidity changes of less than 0.5 nephelometric turbidity units from baseline and pH variations of less than 10% from initial values.</div></div><div><h3>Findings</h3><div>GSH exhibited physical incompatibility with 11 of the 44 intravenous drugs evaluated, while it remained compatible with 33 drugs over 4 hours.</div></div><div><h3>Implications</h3><div>This study reveals that while GSH is physically compatible with the majority of tested intravenous drugs, incompatibilities with 11 drugs under simulated Y-site conditions necessitate rigorous compatibility testing prior to co-administration in clinical settings. These findings emphasize the importance of such testing to prevent potential treatment failures and adverse effects. Further research is needed to explore chemical stability and therapeutic efficacy in clinical settings, ensuring the safe and effective use of GSH in medical treatments.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of Potential Drug Interactions With Direct-Acting Antivirals for COVID-19 Among Hospitalized Patients","authors":"Essy Mozaffari PharmD, MPH, MBA ,&nbsp;Aastha Chandak PhD ,&nbsp;Andrew Ustianowski MD, PhD ,&nbsp;Christina G. Rivera PharmD, RPh ,&nbsp;Neera Ahuja MD, FACP ,&nbsp;Heng Jiang MPH ,&nbsp;Mark Berry PhD ,&nbsp;Jason F. Okulicz MD ,&nbsp;Alpesh N. Amin MD","doi":"10.1016/j.clinthera.2024.08.004","DOIUrl":"10.1016/j.clinthera.2024.08.004","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;Clinicians consider polypharmacy, comorbidities, and other factors including the potential for drug-drug interactions (DDIs) when evaluating therapeutic options for specific clinical diagnoses. Contemporary treatment for coronavirus disease 2019 (COVID-19) includes direct-acting antivirals (DAAs). We sought to characterize patients’ characteristics, comorbidities, and medications received during their hospitalization for COVID-19 and quantify potential DDIs that clinicians consider in selecting appropriate DAAs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Patients hospitalized with a primary diagnosis of COVID-19 between May 2020 and December 2022 from the PINC AI Healthcare Database were identified. Medications administered during the hospitalization with the potential to cause DDIs with nirmatrelvir/ritonavir, remdesivir, or molnupiravir (per the Emergency Use Authorization factsheet or package insert) were assessed. For DDIs with nirmatrelvir/ritonavir, medications are categorized as “Contraindicated,” “Avoid Concomitant Use,” or “Other DDIs” (includes recommendation for dose modification or clinical and laboratory monitoring). For remdesivir, coadministration with chloroquine phosphate and hydroxychloroquine sulfate was not recommended. For molnupiravir, no drugs are listed as having potential DDIs. In a subset of patients, a multivariable logistic regression model was used to examine the association between documented patient/hospital characteristics and the likelihood of being “Contraindicated” to receive nirmatrelvir/ritonavir.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Of the 788,238 patients hospitalized for COVID-19 in 920 hospitals, 53% were ≥ 65 years old, and 31% had Charlson Comorbidity Index (CCI) ≥ 3. During the study period, about half of the patients received medications categorized as “Contraindicated” (11%) and/or “Avoid Concomitant Use” (41%) with nirmatrelvir/ritonavir. The frequency of administered drugs was higher in those aged ≥ 65 years (68%), CCI ≥ 3 (78%), with high-risk underlying conditions (55%). About 1% of patients received medications that were not recommended to be coadmistered with remdesivir. Among a subset of patients hospitalized for COVID-19 in 2022, those who were older, had higher CCI, high-risk underlying conditions, severe hepatic impairment, Medicare insurance, and hospitalized in larger hospitals were significantly more likely to be categorized as “Contraindicated” when considering nirmatrelvir/ritonavir as a therapeutic option to manage COVID-19.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Implications&lt;/h3&gt;&lt;div&gt;A significant proportion of patients hospitalized for COVID-19 receive medications for other conditions that have the potential to result in DDIs with DAAs; most predominantly with nirmatrelvir/ritonavir, a strong CYP3A enzyme inhibitor, fewer with remdesivir, and none with molnupiravir. Higher age and comorbidity burden were significantly associated with a higher likelihood of receiving medications tha","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Hard Work of Developing New Therapies for Pediatric Populations","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2024.09.015","DOIUrl":"10.1016/j.clinthera.2024.09.015","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Pain in Cirrhosis: Advice to Caregivers of Those with Rock Livers","authors":"Randolph E. Regal PharmD","doi":"10.1016/j.clinthera.2024.08.001","DOIUrl":"10.1016/j.clinthera.2024.08.001","url":null,"abstract":"<div><h3>Purpose</h3><div>When one considers the significant role of the liver in medication absorption and metabolism, clinicians must appreciate the important ramifications for medication dosing and monitoring in patients with cirrhosis. For many medications, dose adjustments may be necessary to minimize toxicities or avoid adverse effects from drug accumulation. Clinicians could be well served if they can understand in some detail how pharmacokinetic properties are altered in cirrhosis.</div></div><div><h3>Methods</h3><div>A PubMed search of the English medical literature starting with 1980 using keywords cirrhosis, pain management, and analgesics was performed, and additional papers were found using references from the first round of papers.</div></div><div><h3>Findings</h3><div>Patients with cirrhosis often have significant reductions in first-pass metabolism, altered volumes of distribution, and marked reductions in both renal and hepatic elimination of drugs. These factors may contribute to much higher levels of drug exposure compared to the general population. In terms of drug dosing, FDA labeling is often ambiguous and even incongruous with observed pharmacokinetic changes.</div></div><div><h3>Implications</h3><div>This article may provide guidance for clinicians to optimize pain management in people living with cirrhosis.</div></div><div><h3>Key Message</h3><div>Current FDA labeling for dosing analgesic drugs in patients with cirrhosis is either vague or not consistent with findings from newer pharmacokinetic research. With this review, we hope to provide insight and guidance to clinicians on how to dose-adjust medications commonly utilized in pain management in these patients.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xolremdi—Mavorixafor","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2024.09.007","DOIUrl":"10.1016/j.clinthera.2024.09.007","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}