Pharmacotherapy最新文献

{"title":"Heterogeneous effects of sodium-glucose cotransporter-2 inhibitors compared to dipeptidyl peptidase-4 inhibitors on nephrolithiasis in older adults with type 2 diabetes.","authors":"Rotana M Radwan, Wenxi Huang, Yujia Li, Hui Shao, Yi Guo, Yongkang Zhang, Vivian Fonseca, Lizheng Shi, Yu Huang, Desmond Schatz, Jiang Bian, Jingchuan Guo","doi":"10.1002/phar.70030","DOIUrl":"10.1002/phar.70030","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes (T2D) is associated with an increased risk of nephrolithiasis. Emerging evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT2i) may reduce this risk; however, data remain inconclusive.</p><p><strong>Objective: </strong>To examine the risk of nephrolithiasis among users of SGLT2i compared to dipeptidyl peptidase-4 inhibitors (DPP4i) in a real-world population of older adults with T2D.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using claims data from a sample of national Medicare beneficiaries. Individuals with T2D who initiated SGLT2i or DPP4i therapy between January 1, 2016, and December 31, 2018, were identified. The index date was defined as the date of the first prescription for either SGLT2i or DPP4i, with no prior use of either drug in the preceding year. Patients were followed from the index date until the earliest occurrence of a medical encounter with a primary diagnosis of nephrolithiasis, death, or December 31, 2018. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates, including sociodemographic characteristics, comorbidities, and comedication use. Cox proportional hazards regression models were applied to compare the risk of nephrolithiasis between SGLT2i and DPP4i users. Additional analyses were conducted within subgroups defined by sex, race, and baseline nephrolithiasis status.</p><p><strong>Results: </strong>Of 116,506 included Medicare beneficiaries with T2D (mean age 72 ± 10 years, 53% women), 0.96% developed nephrolithiasis over a median follow-up of 360 days (interquartile range [IQR] 200-467 days). The incidence rate of nephrolithiasis was 9.89 (95% confidence interval [CI] 8.49-11.52) and 11.02 (95% CI 10.34-11.73) events per 1000 person-years in the SGLT2i and DPP4i groups, respectively. After applying IPTW, baseline characteristics were well balanced between the two groups. SGLT2i use was associated with a significantly lower risk of nephrolithiasis compared to DPP4i use (hazard ratio [HR], 0.81; 95% CI 0.66-0.99; p = 0.04). In subgroup analyses, SGLT2i use compared to DPP4i was associated with a significantly lower risk of nephrolithiasis among males (HR 0.75; 95% CI 0.58-0.98; p = 0.04), non-Hispanic Black (NHB) individuals (HR 0.22; 95% CI 0.07-0.64; p < 0.01), and those without baseline nephrolithiasis (HR 0.68; 95% CI 0.53-0.88; p < 0.01).</p><p><strong>Conclusions: </strong>In older adults with T2D, SGLT2i use was associated with a lower risk of nephrolithiasis compared to DPP4i, particularly among men, NHB individuals, and those without baseline nephrolithiasis. Although causality cannot be established, these findings provide real-world evidence supporting a potential benefit of SGLT2is in reducing nephrolithiasis risk, offering valuable insights to guide the selection of glucose-lowering drugs in older adults with T2D.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"426-434"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317624","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":"Predictive performance of population pharmacokinetic models in InsightRX® for model-informed precision dosing for Cefepime.","authors":"Christina König, Joseph L Kuti, Andrew J Fratoni","doi":"10.1002/phar.70029","DOIUrl":"10.1002/phar.70029","url":null,"abstract":"<p><strong>Background: </strong>Model-informed precision dosing (MIPD) is a promising tool used to ensure therapeutic antimicrobial concentrations. Model selection and sampling strategy might lead to different pharmacokinetic (PK) parameter estimates. Herein, we assess the predictive performance for cefepime PK in two models implemented within the InsightRX software using differing sampling approaches.</p><p><strong>Methods: </strong>Historic cefepime PK data and individual Bayesian estimates in predominantly critically ill patients, some of whom had extracorporeal support, served as the reference standard. Two population PK models (A; B) were evaluated using four sampling scenarios: (i) trough only, (ii) midpoint only, (iii) trough + midpoint, and (iv) peak + midpoint + trough. The median prediction error (MPE) and median absolute prediction error (MAPE) were calculated for clearance (CL) and volume of central compartment (V_c). Predicted categorical achievement of ≥70% time that the free drug concentration was greater than the minimum inhibitory concentration [fT>MIC_(8/16mg/L)] was compared.</p><p><strong>Results: </strong>MAPE and MPE for CL and V_c resulted in variability that was dependent on model and sampling strategy. Both models' overall MPE and MAPE for CL were <±20 and <30% for all tested scenarios, respectively, with a low MPE of -2.4% to 4.4% on CL for sampling scenario 4. For V_c, MPE and MAPE were >±20 and >30% for the majority of test scenarios across both models, respectively. When excluding patients with extracorporeal support, MPE/MAPE for V_c decreased to 3.7-4.8/23.3%-34.5% and -7.9-2.5/25.2%-29.6% for model A and B, respectively. Using each model and sampling scheme, only four patients had discordant predicted achievement of ≥70% fT>MIC_(8/16mg/L).</p><p><strong>Conclusions: </strong>These two population PK models and all sampling scenarios demonstrated acceptable prediction of cefepime PK parameters and pharmacodynamic exposures; therefore, they demonstrated suitability for utilizing MIPD for cefepime therapeutic drug monitoring.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"403-413"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049783","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":"Cefepime-taniborbactam: Ushering in the era of metallo-β-lactamase inhibition.","authors":"Sean R Van Helden, Mohammed Al Musawa, Callan R Bleick, Shelbye R Herbin, Michael J Rybak","doi":"10.1002/phar.70036","DOIUrl":"10.1002/phar.70036","url":null,"abstract":"<p><p>Carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CR-PA) continue to pose a significant threat to human health. Furthermore, the prevalence of metallo-β-lactamase (MBL)-producing CRE and CR-PA is increasing, which are capable of hydrolyzing nearly all β-lactam antibiotics. Cefepime-taniborbactam (FTB) is a novel bicyclic boronate β-lactam-β-lactamase inhibitor combination with direct inhibitory activity against MBLs (Ambler Class B), in addition to Ambler Class A, C, and D serine-β-lactamases. FTB has demonstrated high in vitro activity against CRE and CR-PA, including isolates producing NDM, VIM, KPC, AmpC, OXA-48, and extended-spectrum β-lactamases (ESBLs). Furthermore, FTB has demonstrated in vitro activity against Stenotrophomonas maltophilia and Burkholderia cepacia complex. Resistance to FTB is observed in isolates producing IMP, as well as MBL variants NDM-9, NDM-30, and VIM-83. FTB remains susceptible to non-β-lactamase resistance mechanisms, including penicillin-binding protein 3 (PBP3) target mutations. The pharmacodynamic driver of taniborbactam efficacy is the ratio of the area under the curve to the minimum inhibitory concentration (AUC/MIC), and the study dose of FTB 2 g/0.5 g every 8 h infused over 2 h achieves sufficient serum and tissue exposures to maintain therapeutic efficacy. Both components are primarily renally eliminated as unchanged drug; therefore, dose adjustments for renal impairment are required. The clinical efficacy of FTB was demonstrated in the phase III Cefepime Rescue with Taniborbactam in Complicated Urinary Tract Infection (CERTAIN-1) trial, where it demonstrated both non-inferiority and superiority (prespecified analysis) to meropenem in the composite of clinical and microbiologic success at the test of cure for the treatment of complicated urinary tract infection. The safety of FTB was demonstrated throughout its clinical development. Thirteen percent of patients experienced a treatment-related adverse drug event in the phase III clinical trial, with 3% of patients requiring discontinuation of the study agent. Cefepime-taniborbactam appears to be a promising addition to the antibiotic arsenal, particularly as the prevalence of infections caused by MBL-producing organisms continues to rise.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"448-461"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340352","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":"Belzutifan's role in the treatment landscape of clear cell renal cell carcinoma.","authors":"Adrienne H Chen, Allison K Grana","doi":"10.1002/phar.70023","DOIUrl":"10.1002/phar.70023","url":null,"abstract":"<p><p>The treatment of metastatic clear cell renal cell carcinoma (RCC) has changed significantly in the last 20 years with the advent of targeted therapies and immune checkpoint inhibitors. Belzutifan, a hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, has a novel mechanism of action and was approved by the United States Food and Drug Administration (FDA) in 2023 for patients with advanced RCC. In the phase III LITESPARK-005 trial, patients receiving belzutifan had significant improvement in progression-free survival (PFS) compared with everolimus (PFS rate at 12 months: 33.4% vs. 17.1%; PFS rate at 18 months: 24.0% vs. 8.3%, respectively), as well as in objective response rate compared with everolimus (22.7% vs. 3.5%, respectively). There was no significant difference in median overall survival, with 21.4 months for belzutifan and 18.1 months for everolimus (hazard ratio [HR] 0.88; p = 0.20). In clinical practice, patients on belzutifan most often require intervention for anemia and hypoxia. This article describes the current preferred treatment options in clear cell RCC, the pharmacology of belzutifan, clinical trial data for belzutifan in clear cell RCC, our clinical experience with belzutifan and managing associated anemia and hypoxia, and future directions of belzutifan in RCC treatment.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"356-366"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023283","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":"Effect of creatine monohydrate on motor function in children with facioscapulohumeral muscular dystrophy: A multicenter, randomized, double-blind placebo-controlled crossover trial.","authors":"Ian R Woodcock, Katy de Valle, Anita Cairns, Zoe E Davidson, Michael Kean, Nisha Varma, Anneke Grobler, David Metz, Kate Carroll, Nuran Dilek, Chad Heatwole, Monique M Ryan, Martin B Delatycki, Eppie M Yiu","doi":"10.1002/phar.70025","DOIUrl":"10.1002/phar.70025","url":null,"abstract":"<p><strong>Background: </strong>Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive muscle disease with no available disease-modifying therapy. Creatine monohydrate (CrM) has been shown to improve muscle strength in individuals with muscular dystrophies but has not been tested in young people with FSHD. This study aimed to explore the efficacy of CrM on motor function in children with FSHD.</p><p><strong>Methods: </strong>In a randomized placebo-controlled double-blind crossover trial, powdered CrM at a dose of 100 mg/kg/day (maximum 10 g daily) was compared with placebo in two 12-week treatment periods with a 6-week washout between crossover arms. The primary outcome measure was the Motor Function Measure for Neuromuscular Disease (MFM-32) with secondary outcomes assessing safety, endurance, strength, patient-reported outcome measures, and muscle morphology measurements as assessed by whole-body magnetic resonance imaging (MRI).</p><p><strong>Results: </strong>Thirteen children were enrolled (mean (standard deviation, SD) 12.2 (2.67) years of age) and 11 patients completed both trial treatment periods. In an intention-to-treat analysis, no clinically meaningful difference was seen between treatment groups as measured by the mean difference in MFM-32 (0.19, 95% confidence interval (CI) -0.71 to 1.08). However, there was an improvement in 6-minute walk distance of 27.74 m (95% CI -1.41 to 56.88) and trends to improvement in the FSHD-Composite Outcome Measure for Pediatrics (FSHD-COM Peds), 10 meter walk/run, and in MRI measures. There were no serious adverse events. Serum creatinine increased by a mean 12.63 μmol/L (95% CI 1.14 to 24.12) post-CrM treatment, though this was presumed to reflect increased creatinine production. No participants discontinued CrM due to adverse events.</p><p><strong>Conclusion: </strong>CrM is safe and well tolerated in children with FSHD. Although CrM had no effect on motor function as measured by the MFM-32 compared with placebo, there were trends toward improvement in the 6-minute walk distance and other secondary outcome measures. This study confirms the feasibility of conducting clinical trials in children with FSHD. Further assessment of the efficacy of CrM in pediatric FSHD is warranted in a larger randomized controlled clinical trial. Future studies may benefit from stratifying population cohorts according to functional ability or by MRI fat infiltration measurements.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"341-351"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038058","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 of continuous infusion ceftolozane/tazobactam in two patients with extensive total body surface area burns.","authors":"Jay D Olivet, Megan Amerson-Brown, Juan J Calix, Emma Graffice, Tyson Kilpatrick, Hanna F Roenfanz, David P Nicolau, Joseph L Kuti, Matthew L Brown","doi":"10.1002/phar.70019","DOIUrl":"10.1002/phar.70019","url":null,"abstract":"<p><strong>Introduction: </strong>Treatment of infections in patients with burn injuries is challenging due to altered antimicrobial pharmacokinetics. Continuous infusion β-lactam therapy may be a useful antimicrobial stewardship strategy to improve pharmacodynamic target attainment in this population.</p><p><strong>Case summaries: </strong>This report highlights the use of continuous infusion ceftolozane/tazobactam (C/T) in two patients with extensive total body surface area (TBSA) burns, suspected augmented renal clearance (ARC), and bloodstream infections caused by Pseudomonas aeruginosa with difficult-to-treat resistance (DTR P. aeruginosa). Both patients received C/T 9 g/day via continuous infusion. Minimum inhibitory concentrations (MIC) of C/T were 8/4 and 4/4 μg/mL in Cases 1 and 2, respectively.</p><p><strong>Discussion: </strong>Despite similar patient characteristics, average free plasma ceftolozane concentrations were 41.6 mg/L in Case 1 and 22.8 mg/L in Case 2. Measured free concentrations exceeded 4 times the MIC for 100% of each 24-h infusion (fT > 4xMIC), and bacteremia was successfully cleared in each case.</p><p><strong>Conclusion: </strong>These cases highlight the variability of drug exposure in patients with extensive TBSA burn injuries and support continuous infusion β-lactam therapy as a proactive strategy to optimize pharmacodynamic target attainment when pharmacokinetics are unpredictable.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"386-392"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024847","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":"Pharmacotherapy research landscape and knowledge gaps of opioids in maternal and pediatric populations.","authors":"Aditi Shendre, Xiaofu Liu, ChienWei Chiang, Andrew Goodwin, Samuel-Richard Oteng, Jiezel A F Deypalubos, Shijun Zhang, Lei Wang, Jianing Liu, Mohammad Yaseen Abbasi, Blessed Winston Aruldhas, Syed Saoud Zaidi, Lindsey Marie Kirkpatrick, Lais Da Silva, Brian R Overholser, Aislinn M O'Kane, Prince J Kannankeril, Stephen W Patrick, Andrew D Wiese, Sara K Quinney, Lang Li","doi":"10.1002/phar.70024","DOIUrl":"10.1002/phar.70024","url":null,"abstract":"<p><p>The use and misuse of opioids has surged in the past decade, with nearly half of the users being female. Although opioid use is lower among pregnant women, trends mirror the general population. While pediatric exposures largely occur through prescriptions. This review presents a novel landscape analysis of pharmacology knowledge gaps in opioids in the maternal and pediatric populations. We queried PubMed for studies on 27 opioids, focusing on pharmacokinetics (PK), and pharmacoepidemiology (PE) or clinical trials (CT) in maternal and pediatric populations. English-language publications were included, and data were synthesized to identify gaps. Additionally, MarketScan claims data and United States Food and Drug Administration (FDA) drug labels were analyzed to compare scientific evidence, opioid prescriptions/orders, and FDA recommendations. Morphine, fentanyl, methadone, and buprenorphine are the most researched opioids in PK and PE/CT literature in both populations, but hydrocodone, oxycodone, and codeine are the most prescribed. Nine opioids lack FDA labels, and four of the 18 labeled drugs lack any human data. Hydrocodone, oxycodone, and codeine labels include lactation-focused PK information, with some pediatric clinical data for the latter two. Seven opioids lack PK and PE/CT studies in the maternal population, and PK research is absent for seven opioids, and PE/CT data is lacking for eight opioids in the pediatric population. PK studies often focus on labor, delivery, and lactation accompanied by neonatal data, whereas pregnancy research mainly occurs in PE studies. In pediatric populations, study types are evenly distributed among children, but PE studies focus more on adolescents. Drug concentration is the most reported parameter in PK studies, and neonatal opioid withdrawal syndrome (NOWS) is a key outcome in both PK and PE studies. NOWS is also researched more using real-world data, whereas neurodevelopmental outcomes are often captured in prospective observational studies. There is substantial disparity between the most commonly researched and prescribed opioids. In particular, the opioid pharmacology knowledge gaps are larger in pregnant women and for the highly prescribed opioids hydrocodone and oxycodone. The limited human data in FDA labels underscores the need for additional studies. Studies using real-world data can potentially help address these gaps.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"367-385"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079548","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":"Fluoroquinolones and the risk of aortic aneurysm or dissection: A population-based propensity score-matched German cohort study.","authors":"Julia Wicherski, Jonas Peltner, Cornelia Becker, Katrin Schüssel, Gabriela Brückner, Andreas Schlotmann, Helmut Schröder, Winfried V Kern, Britta Haenisch","doi":"10.1002/phar.70020","DOIUrl":"10.1002/phar.70020","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the risk of aortic aneurysm or dissection associated with fluoroquinolone (FQ) prescription compared to macrolides in German routine health care data in order to replicate the recent study (Pharmacotherapy 2023;43:883) extending the results by contributing evidence for six additional broad-spectrum antibiotic classes as active comparators.</p><p><strong>Design: </strong>Cohort study in active comparator new user design comparing FQ with macrolides, tetracyclines, penicillins with extended spectrum, penicillins and beta-lactamase inhibitor combinations, second- and third-generation cephalosporins, sulfonamide and trimethoprim combinations, and lincosamides.</p><p><strong>Setting: </strong>German statutory health insurance, the \"Allgemeine Ortskrankenkasse\" (AOK), January 2013 to December 2019.</p><p><strong>Participants: </strong>Adults with at least one new prescription fill for FQ or active comparator antibiotics. New users were defined as individuals without antibiotic prescription fills, aortic aneurysm or dissection diagnoses, and hospitalization within 365 days prior to the cohort entry date. Users of FQ and active comparators were matched by nearest neighbor 1:1 propensity score matching.</p><p><strong>Main outcome measures: </strong>Incident inpatient aortic aneurysm or dissection was observed within a 60-day risk window. In sensitivity analyses, an extended risk window of 90 days was applied, and specific FQ agents, dosages, and diagnoses were stratified.</p><p><strong>Results: </strong>FQ episodes were associated with an increased risk for aortic aneurysm or dissection compared to macrolides (aHR = 1.52 [1.33; 1.74]), which replicates the risk estimate of Garg et al. (aHR = 1.34 [1.17; 1.54]). This association was robust in a 90-day risk window and for ciprofloxacin, levofloxacin, and moxifloxacin. Moxifloxacin comprised the greatest risk of aortic aneurysm or dissection compared to macrolides (aHR = 2.13 [1.64; 2.77]). Moreover, we observed similar associations when comparing FQ to tetracyclines, penicillins with extended spectrum, cephalosporins, and lincosamides (aHR = 1.86 [1.54; 2.24], aHR = 1.45 [1.28; 1.65], aHR = 1.23 [1.10; 1.37], and aHR = 1.73 [1.43; 2.11]), respectively.</p><p><strong>Conclusion: </strong>In a German cohort study, FQ use was associated with a 52% increased risk for aortic aneurysm or dissection within 60 days compared with macrolide use. The risk of FQ-associated aortic aneurysm or dissection compared to macrolides can be replicated in German routine health care data. Extending the analysis, we provided new insights that the effect size may depend on the chosen AC.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"314-323"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987749","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":"Chloride dipstick to rapidly estimate urine sodium during diuresis in acute heart failure.","authors":"V Shah, David Cordwin, Scott L Hummel, Michael P Dorsch","doi":"10.1002/phar.70026","DOIUrl":"10.1002/phar.70026","url":null,"abstract":"<p><strong>Background: </strong>Rapid assessment of diuretic efficacy is necessary in the treatment of acute decompensated heart failure. European guidelines advocate for the use of spot urinary sodium measurements, but recent data suggest urinary chloride is the better marker. Laboratory turnaround, however, delays clinical decision-making. We tackle this by using a commercially available chloride urinary dipstick to estimate sodium and measure chloride.</p><p><strong>Methods: </strong>This was a prospective pilot study involving patients hospitalized at the University of Michigan for acute decompensated heart failure (ADHF) with an indication for intravenous diuresis; patients were eligible for enrollment within 24 h of admission. Patients with end-stage kidney disease or receiving continuous loop diuretic infusions or thiazide-type diuretics were excluded. A spot urine sample was collected after the loop diuretic dose. A chloride dipstick was used, and results were compared against laboratory-obtained measurements of urinary chloride and sodium.</p><p><strong>Results: </strong>In a total of 22 patients (mean age 62.2 ± 11.8 years, 50% female, and LVEF 31.8 ± 17.4%), dipstick chloride concentrations correlated highly with laboratory-measured urine chloride (r = 0.98, p < 0.001) with slight overestimation across the physiological range and with laboratory-measured urine sodium (r = 0.86, p < 0.001), although with greater variation. Dipstick interpretation preceded laboratory results by a median of 136 minutes (IQR 103-170, p < 0.001).</p><p><strong>Conclusions: </strong>The chloride dipstick rapidly and accurately assessed urine chloride almost 2 h faster than traditional laboratory output in patients undergoing diuresis for ADHF. It may be a new tool to evaluate loop diuretic treatment for ADHF. However, more studies are needed to assess its impacts on clinical outcomes.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"352-355"},"PeriodicalIF":3.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111007","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 of posaconazole concentrations for hypoalbuminemia.","authors":"David E Nix, Fekade Sime, Jason A Roberts","doi":"10.1002/phar.70021","DOIUrl":"10.1002/phar.70021","url":null,"abstract":"<p><strong>Background: </strong>Posaconazole is an example of a highly protein-bound drug (>98%) in which therapeutic drug monitoring (TDM) is commonplace. Total drug concentration is typically measured, and in the setting of hypoalbuminemia, total concentrations are lower despite no anticipated change in unbound concentration. Data support that unbound posaconazole concentration is responsible for antifungal activity and, in theory, is responsible for adverse effects that are dose-related. However, the therapeutic range of posaconazole is expressed as total concentration. The objective of this study was to investigate the use of an equation to correct posaconazole concentrations for albumin concentration as a surrogate for measurement of unbound concentration.</p><p><strong>Methods: </strong>Data on unbound and total posaconazole concentration were acquired retrospectively from a study of posaconazole pharmacokinetics in critically ill patients. The relationship between total and unbound concentration was explored with and without albumin as a covariate using linear regression. Correction equations were used to normalize total concentration to an albumin concentration of 4.4 g/dL.</p><p><strong>Results: </strong>A total of 78 pairs of total and unbound concentrations were available. Total and unbound posaconazole concentrations were determined using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The median fraction unbound was 0.00645 (interquartile range of 0.00331-0.00794). Albumin concentration plays a highly significant role in the interpretation of TDM results. In a patient with hypoalbuminemia, a corrected concentration (C_corr) = C_t/(0.01 + 0.99·Alb/4.4), where C_t is the total concentration and Alb is the albumin concentration in units of g/dL, is suggested. This equation can be further simplified to C_sim = C_t·4.4/Alb, where C_sim is a close approximation of C_corr.</p><p><strong>Conclusions: </strong>Hypoalbuminemia is associated with lower total concentrations of posaconazole; however, the \"active\" unbound concentration is not expected to systematically change. As a result, total posaconazole concentrations in the therapeutic range for patients with hypoalbuminemia are more likely to be associated with toxicity, especially when doses are increased to achieve \"therapeutic\" concentrations.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"324-331"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977480","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}