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Relationship of the revised anticholinergic drug scale with cultured cell-based serum anticholinergic activity and cognitive measures in older adults with mild cognitive impairment or remitted depression. 修订抗胆碱能药物量表与轻度认知障碍或抑郁症缓解的老年人培养细胞血清抗胆碱能活性和认知功能的关系
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-06-01 Epub Date: 2025-05-06 DOI: 10.1002/phar.70022
Ryan M Carnahan, Susmita Chandramouleeshwaran, Naba Ahsan, Roger Raymond, Jose N Nobrega, Wei Wang, Corinne E Fischer, Alastair J Flint, Nathan Herrmann, Sanjeev Kumar, Krista L Lanctôt, Linda Mah, Benoit H Mulsant, Bruce G Pollock, Tarek K Rajji
{"title":"Relationship of the revised anticholinergic drug scale with cultured cell-based serum anticholinergic activity and cognitive measures in older adults with mild cognitive impairment or remitted depression.","authors":"Ryan M Carnahan, Susmita Chandramouleeshwaran, Naba Ahsan, Roger Raymond, Jose N Nobrega, Wei Wang, Corinne E Fischer, Alastair J Flint, Nathan Herrmann, Sanjeev Kumar, Krista L Lanctôt, Linda Mah, Benoit H Mulsant, Bruce G Pollock, Tarek K Rajji","doi":"10.1002/phar.70022","DOIUrl":"10.1002/phar.70022","url":null,"abstract":"<p><strong>Objective: </strong>The Anticholinergic Drug Scale (ADS) is a commonly used measure of anticholinergic exposure. This study describes an expanded and revised version of the ADS (rADS) and its relationship with cultured cell-based serum anticholinergic activity (cSAA) and cognitive measures.</p><p><strong>Study participants: </strong>Adults aged 60 years and older with mild cognitive impairment (MCI), remitted major depressive disorder (rMDD), or both, participate in the Prevention of Alzheimer's Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study.</p><p><strong>Study design: </strong>Cross-sectional investigation of data from the PACt-MD study.</p><p><strong>Measures: </strong>The rADS includes ratings for 1047 distinct products, about twice as many as the originally published scale; previously published ratings were revised for 40 drugs. Total rADS scores were calculated as sums of ratings of all drugs taken by participants; cSAA was measured in the participants' sera; cognitive performance included measures of executive function, language, processing speed, verbal memory, visuospatial memory, working memory, and an overall composite score.</p><p><strong>Statistical analysis: </strong>The relationship between rADS total scores and cSAA was examined using a Spearman rank correlation coefficient. Relationships between rADS total scores and cognitive performance measures were explored in multivariable linear regression models.</p><p><strong>Results: </strong>The sample included 310 participants (mean [standard deviation] age: 72 (6) years; 61.6% were women, and 81.6% had MCI [with or without rMDD]). Total rADS scores were positively correlated with cSAA (Spearman's correlation coefficient: 0.178, p = 0.0016). Total rADS scores were not significantly associated with cognitive performance.</p><p><strong>Conclusions: </strong>The revised scale is recommended as a replacement for the original ADS since it includes ratings for more drugs and was significantly, albeit weakly, associated with cSAA, similar to previous findings using the original ADS.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"332-340"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011346","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}
引用次数: 0
Response to comment on "Association of atrial fibrillation with lamotrigine: An observational cohort study". 对“拉莫三嗪与房颤的关联:一项观察性队列研究”评论的回应。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-05-01 Epub Date: 2025-05-08 DOI: 10.1002/phar.70016
Sodam Kim, Landon Welch, Bertha De Los Santos, Przemysław B Radwański, Mark A Munger, Kibum Kim
{"title":"Response to comment on \"Association of atrial fibrillation with lamotrigine: An observational cohort study\".","authors":"Sodam Kim, Landon Welch, Bertha De Los Santos, Przemysław B Radwański, Mark A Munger, Kibum Kim","doi":"10.1002/phar.70016","DOIUrl":"10.1002/phar.70016","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"308-309"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020941","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}
引用次数: 0
Retrospective cohort study of oral switch versus intravenous antibiotics for carbapenem-resistant enterobacterales and Pseudomonas aeruginosa infections on hospital discharge. 对出院时耐碳青霉烯肠杆菌和铜绿假单胞菌感染口服与静脉注射抗生素的回顾性队列研究。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-05-01 Epub Date: 2025-05-09 DOI: 10.1002/phar.70012
Christen J Arena, Ali Abed, Rachel M Kenney, Geehan Suleyman, Anita Shallal, Susan L Davis, Michael P Veve
{"title":"Retrospective cohort study of oral switch versus intravenous antibiotics for carbapenem-resistant enterobacterales and Pseudomonas aeruginosa infections on hospital discharge.","authors":"Christen J Arena, Ali Abed, Rachel M Kenney, Geehan Suleyman, Anita Shallal, Susan L Davis, Michael P Veve","doi":"10.1002/phar.70012","DOIUrl":"10.1002/phar.70012","url":null,"abstract":"<p><strong>Objectives: </strong>To compare outcomes of oral switch versus intravenous antibiotics for the treatment of carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) infections at hospital discharge.</p><p><strong>Methods: </strong>Institutional review board approved, retrospective cohort of adults infected with CRE or CRPA who received oral switch or intravenous antibiotics at hospital discharge from January 1, 2017, to April 30, 2024. Patients were included if they were eligible for oral switch and infected with an isolate susceptible to one or more oral antibiotics; non-bacteremic urinary tract infections were excluded. The primary outcome was 30-day clinical success at end of therapy, defined as lack of infection-related hospitalization, infection-related recurrence, or change/escalation of therapy. Secondary outcomes included hospital length of stay (LOS) and 30-day all-cause mortality from end of therapy.</p><p><strong>Results: </strong>Fifty-five patients were included; 51% received oral switch antibiotics and 49% received intravenous antibiotics. Thirty-three percent of patients had CRE, 67% had CRPA, and 38% of cultures were polymicrobial. The most common infection types were pneumonia (33%), intra-abdominal (26%), and bone/joint (22%). The median (interquartile range [IQR]) duration of outpatient therapy was 12 (6-25) days versus 20 (4-34) days for the oral switch and intravenous antibiotic groups, respectively (p = 0.341). 30-day clinical success was 61% in the oral switch and 48% in the intravenous antibiotic groups (p = 0.349); the median (IQR) hospital LOS for the oral switch and intravenous antibiotic groups was 14 (9-25) days and 16 (9-49) days, respectively (p = 0.165); 30-day mortality was 4% in the oral switch group and 15% in the intravenous antibiotic group (p = 0.193).</p><p><strong>Conclusion: </strong>A limited sample of patients who received oral switch antibiotics had similar outcomes to intravenous outpatient treatment of carbapenem-resistant organisms, with a shorter hospital LOS.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"244-250"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987754","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}
引用次数: 0
Risk of acute kidney injury in dapagliflozin users with type 2 diabetes: A nationwide propensity score-matched cohort study in Korea. 达格列净使用者合并2型糖尿病的急性肾损伤风险:韩国一项全国性倾向评分匹配队列研究
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-05-01 Epub Date: 2025-04-11 DOI: 10.1002/phar.70015
Hee-Jin Kim, Heehyun Won, Suvin Park, Hui-Eon Lee, Haerin Cho, Jeong Ah Kim, Na-Young Jeong, HoJin Shin, Ye-Jee Kim, Nam-Kyong Choi
{"title":"Risk of acute kidney injury in dapagliflozin users with type 2 diabetes: A nationwide propensity score-matched cohort study in Korea.","authors":"Hee-Jin Kim, Heehyun Won, Suvin Park, Hui-Eon Lee, Haerin Cho, Jeong Ah Kim, Na-Young Jeong, HoJin Shin, Ye-Jee Kim, Nam-Kyong Choi","doi":"10.1002/phar.70015","DOIUrl":"10.1002/phar.70015","url":null,"abstract":"<p><strong>Background: </strong>Several previous studies have identified a potential risk of acute kidney injury (AKI) associated with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, based on adverse event reports. However, recent European observational studies have shown conflicting results.</p><p><strong>Objective: </strong>To evaluate the risk of AKI in patients with type 2 diabetes (T2DM) who were treated with dapagliflozin compared with sitagliptin.</p><p><strong>Method: </strong>We conducted a retrospective cohort study on patients with T2DM who were newly prescribed dapagliflozin or sitagliptin between September 1, 2014, and June 30, 2021, using the nationwide National Health Insurance Review and Assessment (HIRA) Service database in Korea. Propensity scores were estimated using a multivariable logistic regression model, and matching was performed at a 1:1 ratio to balance the dapagliflozin and sitagliptin groups. The outcome of interest was the occurrence of AKI hospitalization 90 days post-exposure, captured by a validated algorithm based on the International Classification of Diseases 10th Revision (ICD-10) code: N17. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using a Cox proportional hazards model.</p><p><strong>Results: </strong>Among 94,977 dapagliflozin users matched to sitagliptin users, AKI events occurred in 132 dapagliflozin users versus 198 sitagliptin users, with incidence rates of 2.92 and 8.93 per 1000 person-years, respectively. The risk of AKI events was 34% lower in dapagliflozin users (HR: 0.66, 95% CI: 0.53-0.83) compared with sitagliptin users. This protective effect remained consistent in sensitivity analyses.</p><p><strong>Conclusion: </strong>Contrary to the United States Food and Drug Administration's safety warning, our findings suggest that dapagliflozin may have a protective effect against AKI in patients with T2DM. This is consistent with recent findings from European post-marketing safety studies and may serve as supportive evidence.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"282-290"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049800","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}
引用次数: 0
Efficacy of adjuvant use of midodrine in patients with septic shock: An open label randomized controlled trial. midodrine辅助治疗感染性休克的疗效:一项开放标签随机对照试验。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-05-01 Epub Date: 2025-04-16 DOI: 10.1002/phar.70018
Nadine K El-Nagdy, Noha O Mansour, Adel Al-Hady Ahmed Diab, Moetaza M Soliman
{"title":"Efficacy of adjuvant use of midodrine in patients with septic shock: An open label randomized controlled trial.","authors":"Nadine K El-Nagdy, Noha O Mansour, Adel Al-Hady Ahmed Diab, Moetaza M Soliman","doi":"10.1002/phar.70018","DOIUrl":"10.1002/phar.70018","url":null,"abstract":"<p><strong>Background: </strong>Midodrine has been primarily studied as an adjunctive oral therapy to reduce the need for vasopressors in intensive care units (ICU). Nonetheless, the available results evaluating midodrine as an adjuvant therapy in the treatment of septic shock are limited and inconclusive. This study aims to evaluate the efficacy of midodrine, specifically focusing on its effect on mortality outcomes in patients with septic shock.</p><p><strong>Methods: </strong>This was an open-label randomized controlled trial. Patients with septic shock (n = 100) were randomized to either the control group, who received intravenous norepinephrine, or the midodrine group, who received intravenous norepinephrine and midodrine 10 mg every 8 h. The primary outcome was the 28-day in-hospital mortality. Secondary outcomes were 7-day ICU mortality, average dose of norepinephrine, duration of intravenous norepinephrine, ICU length of stay (LOS), and in-hospital LOS.</p><p><strong>Results: </strong>The 28-day mortality rate was 68% in the control group compared to 54% in the midodrine group (risk difference -14% (95% confidence interval (CI)) -32.9% to 4.9%). Similarly, the 7-day ICU mortality rate was 56% in the control group and 42% in the midodrine group (risk difference -14% (95% CI -33.4% to 5.4%)). The average intravenous norepinephrine dose in the midodrine group was significantly lower compared to the control group (mean difference 0.06 (95% CI 0.01-0.11), p = 0.002). However, midodrine did not have a significant impact on the duration of intravenous norepinephrine use (mean difference 0.66 (95% CI -0.56 to 1.88)). Midodrine did not significantly shorten the course of hospitalization. There was no significant difference in median ICU LOS between the control group and the midodrine group (4 vs. 5 days, respectively).</p><p><strong>Conclusion: </strong>The findings did not demonstrate a significant reduction in mortality with adjuvant midodrine use in the treatment of septic shock. Midodrine appears to reduce the need for vasopressors. However, our findings did not support that midodrine shortens the duration of vasopressor use nor the course of hospitalization for patients with septic shock.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"264-272"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020940","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}
引用次数: 0
Better together? Reducing vancomycin use and acute kidney injury with a blended AUC and trough-based dosing guideline. 更好的在一起吗?使用AUC和槽型给药指南减少万古霉素的使用和急性肾损伤。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-05-01 Epub Date: 2025-03-24 DOI: 10.1002/phar.70011
Alyssa Christensen, Ethan Ryberg, Zachary Nelson, Ella Chrenka, Maxx Enzmann, S Rebecca Peglow, Brent Footer
{"title":"Better together? Reducing vancomycin use and acute kidney injury with a blended AUC and trough-based dosing guideline.","authors":"Alyssa Christensen, Ethan Ryberg, Zachary Nelson, Ella Chrenka, Maxx Enzmann, S Rebecca Peglow, Brent Footer","doi":"10.1002/phar.70011","DOIUrl":"10.1002/phar.70011","url":null,"abstract":"<p><strong>Background: </strong>Vancomycin guidelines recommend area-under-the-curve (AUC) therapeutic monitoring for patients with severe methicillin-resistant Staphylococcus aureus (MRSA) infections. No recommendations exist for patients with non-severe staphylococcal infections or those with other Gram-positive infections. AUC-based vancomycin dosing can be resource-intensive and may not be necessary for all patients.</p><p><strong>Methods: </strong>New institutional guidelines for vancomycin dosing were implemented across an eight-hospital health system in 2023. The new guidelines recommended either AUC or trough-based dosing depending on the severity of the infection and the likelihood of MRSA. Adult patient encounters with at least one vancomycin administration were compared retrospectively 6 months pre-implementation and 6 months post-implementation. Cumulative vancomycin dose, administrations, and serum levels were assessed. The rate of acute kidney injury (AKI) was compared in a subgroup of patient encounters with four or more administrations. Pharmacist time saved using a blended approach compared to a uniform AUC dosing guideline was estimated based on the number of patients receiving trough-based dosing in the post-implementation group.</p><p><strong>Results: </strong>A total of 8155 patient encounters were included in the analysis (3916 pre-implementation, 4239 post-implementation). The primary outcome of median cumulative vancomycin dose (mg) was 500 mg lower in the post-implementation group (3000 mg pre-implementation vs 2500 mg post-implementation, Odds ratio [OR] 0.94 95% confidence interval [CI] 0.90-0.97, p < 0.001). Patients in the post-implementation group were significantly less likely to have vancomycin serum levels drawn (OR 0.86; 95% CI 0.78, 0.96, p = 0.005). A subgroup of patient encounters receiving four or more vancomycin administrations included 2483 patient encounters (1251 pre-implementation, 1232 post-implementation). AKI occurred in 120 (9.6%) cases pre-implementation and 89 (7.2%) cases post-implementation. The risk of AKI was significantly lower post-implementation (OR 0.73; 95% CI 0.55, 0.98, p = 0.038). Estimated pharmacist time saved was between 2229 to 5201 min, equating to an estimated $16,851.24 to $39,319.56 saved over 6 months, with blended vancomycin dosing.</p><p><strong>Conclusion: </strong>In this large multi-hospital cohort, the implementation of a blended dosing method using a majority of AUC-based dosing reduced cumulative vancomycin doses, serum levels, and AKI. Including trough recommendations for patients with less severe infections and non-MRSA, Gram-positive pathogens may have saved significant pharmacist time and associated costs compared to a uniform AUC dosing policy. This study further highlights the sizeable amount of unnecessary vancomycin use with a corresponding low incidence of severe MRSA infections.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"273-281"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692873","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}
引用次数: 0
Comment on "Association of atrial fibrillation with lamotrigine: An observational cohort study". 对“拉莫三嗪与房颤的关联:一项观察性队列研究”的评论。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-05-01 Epub Date: 2025-04-09 DOI: 10.1002/phar.70017
Kui Dang, Youbin Luo
{"title":"Comment on \"Association of atrial fibrillation with lamotrigine: An observational cohort study\".","authors":"Kui Dang, Youbin Luo","doi":"10.1002/phar.70017","DOIUrl":"10.1002/phar.70017","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"307"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811980","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}
引用次数: 0
Updates in chronic kidney disease management: A systematic review. 慢性肾脏疾病管理的最新进展:一项系统综述。
IF 3.4 3区 医学
Pharmacotherapy Pub Date : 2025-05-01 Epub Date: 2025-03-28 DOI: 10.1002/phar.70014
Amina Ammar, Stephanie B Edwin, Rachel Whitney, Melissa Lipari, Christopher Giuliano
{"title":"Updates in chronic kidney disease management: A systematic review.","authors":"Amina Ammar, Stephanie B Edwin, Rachel Whitney, Melissa Lipari, Christopher Giuliano","doi":"10.1002/phar.70014","DOIUrl":"10.1002/phar.70014","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is a significant global health challenge that impacts both patients and the health care system. This systematic review aims to evaluate the efficacy and safety of emerging therapeutic strategies for CKD management, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), finerenone, sacubitril/valsartan, and potassium binders. We conducted searches in databases including PubMed, Scopus, CINAHL Complete, and Web of Science Core Collection to identify experimental and observational studies pertaining to each of these agents. Included studies were those that enrolled adult patients with CKD who evaluated SGLT2i, GLP-1RA, finerenone, sacubitril/valsartan, and potassium binders compared to other medications or placebo and evaluated renal-related outcomes as a primary or secondary outcome. Methodological quality and risk of bias were assessed using the Cochrane Risk of Bias (version 2) tool for experimental studies and ROBINS-I for observational studies. After screening 2135 unique studies, 138 studies were eligible for this review. These studies describe a substantial and growing body of evidence focused on improving the management of CKD beyond renin-angiotensin system inhibitors (RASi), such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). Currently, SGLT2i have demonstrated consistent benefits with large effect sizes in preventing the progression of CKD, solidifying this class as a first-line treatment along with RASi. Subsequent consideration for GLP-1RA, finerenone, and sacubitril/valsartan should be dependent on patient-specific comorbidities, while potassium binders may allow for longer use of RASi.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"291-306"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730793","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}
引用次数: 0
Pharmacokinetic approaches to standardize antiviral exposure in cerebrospinal fluid. 规范脑脊液中抗病毒药物暴露的药代动力学方法。
IF 3.4 3区 医学
Pharmacotherapy Pub Date : 2025-05-01 Epub Date: 2025-03-28 DOI: 10.1002/phar.70013
Sean N Avedissian, Ying Mu, Caitlyn McCarthy, Ronald J Bosch, Serena Spudich, Rajesh T Gandhi, Deborah K McMahon, Joseph J Eron, John W Mellors, Jiajun Liu, Anthony T Podany, Courtney V Fletcher
{"title":"Pharmacokinetic approaches to standardize antiviral exposure in cerebrospinal fluid.","authors":"Sean N Avedissian, Ying Mu, Caitlyn McCarthy, Ronald J Bosch, Serena Spudich, Rajesh T Gandhi, Deborah K McMahon, Joseph J Eron, John W Mellors, Jiajun Liu, Anthony T Podany, Courtney V Fletcher","doi":"10.1002/phar.70013","DOIUrl":"10.1002/phar.70013","url":null,"abstract":"<p><strong>Objectives: </strong>HIV has been shown to persist in the central nervous system (CNS) in persons on antiretroviral therapy (ART). Our objective was to use pharmacokinetic (PK) modeling to estimate cerebrospinal fluid (CSF) exposure from time-variant concentrations of various antiretrovirals of ART regimens and to standardize CSF metrics, including maximum concentration [C<sub>MAX</sub>], area under the curve [AUC], and trough [C<sub>Trough</sub>].</p><p><strong>Methods: </strong>Advancing Clinical Therapeutics Globally (ACTG) A5321 is a prospective cohort study of HIV-1 reservoirs in persons with HIV. Plasma and CSF antiretroviral (ARV) concentrations were measured in 74 participants who were receiving ART. PK modeling (Pmetrics) was performed for nine ARVs. Relative CSF penetration for each ARV was estimated by comparing CSF C<sub>MAX</sub> and AUC to plasma C<sub>MAX</sub> and AUC (i.e., C<sub>MAXmethod</sub> and AUC<sub>method</sub>). The CSF C<sub>Trough</sub> for each ARV was compared with in vitro literature values of HIV inhibitory concentration values (IC<sub>50, 90, or 95</sub>).</p><p><strong>Results: </strong>Emtricitabine exhibited the highest median relative CSF penetration (C<sub>MAXmethod</sub>, 46.3%; AUC<sub>method</sub>, 72%) and dolutegravir had the lowest CSF penetration (C<sub>MAXmethod</sub>, 0.57%; AUC<sub>method</sub>, 0.57%). Tenofovir, lamivudine, atazanavir, and raltegravir had median estimated CSF C<sub>Trough</sub> concentrations less than IC<sub>50, 90, or 95</sub>. Interparticipant variability of relative CSF penetration based on exposures ranged from 160% for lamivudine to approximately 9% for dolutegravir.</p><p><strong>Conclusions: </strong>PK modeling successfully standardized ARV CSF concentrations to a given time point (i.e., C<sub>MAX</sub> or C<sub>Trough</sub>) to allow estimation of CSF penetration. This approach provides uniformity for the assessment of exposure, for the estimation of whether desired therapeutic drug goals are obtained in the CSF, and for further studies to investigate whether CSF exposure metrics calculated using this method are associated with measures of HIV persistence.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"251-263"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730774","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}
引用次数: 0
Response to comment on "Use of proton pump inhibitors and risk of severe COVID-19: A case-control study in United States Medicare beneficiaries". 对“质子泵抑制剂的使用与严重COVID-19风险:美国医疗保险受益人的病例对照研究”评论的回应。
IF 2.9 3区 医学
Pharmacotherapy Pub Date : 2025-04-01 DOI: 10.1002/phar.70003
Andrew D Mosholder, Michael Wernecke, David J Graham
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