Pharmacotherapy最新文献

{"title":"Association between mineralocorticoid receptor antagonists and kidney harm: A systematic review and meta-analysis of randomized controlled trials.","authors":"Satoru Mitsuboshi, Makoto Morizumi, Shungo Imai, Satoko Hori, Kazumasa Kotake","doi":"10.1002/phar.4618","DOIUrl":"10.1002/phar.4618","url":null,"abstract":"<p><p>Conflicting data have been reported on the association between mineralocorticoid receptor antagonists (MRAs) and acute kidney injury (AKI). This systematic review and meta-analysis aimed to evaluate whether MRAs affect the risk of AKI. MEDLINE via PubMed, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov website were comprehensively searched to extract all relevant studies. Randomized controlled trials (RCTs) were selected that compared MRA versus placebo or no treatment and had study populations consisting of patients with heart or kidney disease. The primary outcome was AKI. The secondary outcome was kidney injury, including AKI and non-AKI. Thirty-three studies were included in the meta-analysis. MRAs were not associated with an increased risk of AKI (risk ratio [RR] 1.13, 95% confidence interval [CI] 0.88-1.46, p = 0.29, I² = 15%, 18,065 patients, 13 RCTs, moderate certainty). For the secondary outcome, MRAs were associated with an increased risk of kidney injury (RR 1.52, 95% CI 1.24-1.87, p < 0.01, I² = 48%, 27,492 patients, 33 RCTs, low certainty). In particular, only canrenone (RR 5.39, 95% CI 2.17-13.37, p < 0.01) and spironolactone (RR 1.78, 95% CI 1.48-2.14, p < 0.01) were associated with an increased risk of kidney injury. However, eplerenone and finerenone seem not to increase the risk of kidney injury in patients with heart or kidney disease. The selection of MRAs might influence the risk of kidney-associated events. Further studies focusing on individual MRAs may be needed to clarify these differences.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"43-53"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693137","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":"Utilization and associated factors of TPMT testing among Australian adults receiving thiopurines: A national retrospective data-linkage study.","authors":"Chin Hang Yiu, Bella D Ianni, Kenji Fujita, Edwin C K Tan, Sarah N Hilmer, Christine Y Lu","doi":"10.1002/phar.4631","DOIUrl":"10.1002/phar.4631","url":null,"abstract":"<p><strong>Introduction: </strong>Thiopurine drugs are metabolized by thiopurine methyltransferase (TPMT) and low TPMT activity can result in severe adverse drug reactions. Therefore, TPMT testing is recommended for individuals receiving thiopurines to reduce the risk of toxicity.</p><p><strong>Objectives: </strong>The objectives of this study were to assess the rate of TPMT testing among individuals receiving thiopurines and explore factors associated with undergoing TPMT testing in Australia.</p><p><strong>Methods: </strong>This retrospective cohort study utilized administrative data from the Pharmaceutical Benefits Scheme (PBS), Medicare Benefits Schedule (MBS), and the 2021 Census, accessed via the Person Level Integrated Data Asset (PLIDA) at the Australian Bureau of Statistics (ABS) DataLab. Individuals receiving thiopurines aged 18 years or above were identified using PBS data and exposure to TPMT testing was determined using MBS data. Multivariate logistic regression was performed to identify factors associated with TPMT testing.</p><p><strong>Results: </strong>A total of 62,574 prevalent thiopurine users were identified between 2020 and 2022. Of these, 20,327 (32.5%) underwent TPMT testing (2011-2022). The most significant factor associated with TPMT testing was having at least one thiopurine medication prescribed by a medical specialist (adjusted odds ratio [aOR] 2.12, 95% confidence interval [CI] 2.02-2.22), compared to having medication solely prescribed by primary care physicians (PCPs). Other significant factors associated with TPMT testing included speaking a non-English language at home (aOR 1.29, 95% CI 1.22-1.36), having no chronic health conditions (aOR 1.18, 95% CI 1.13-1.24), not requiring assistance with core activities (aOR 1.16, 95% CI 1.08-1.23), and having a higher educational attainment (aOR 1.11, 95% CI 1.06-1.11). Compared to living in major cities, individuals living in remote areas were significantly less likely to undergo testing (aOR 0.49, 95% CI 0.39-0.60).</p><p><strong>Conclusion: </strong>Our study highlights the low utilization of TPMT testing in Australia and suggests the need for targeted interventions to address disparities and improve TPMT testing.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"12-19"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716819","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":"Scoping review of drug dosing recommendations in sustained low-efficiency dialysis.","authors":"Nicholas R Nelson, Nicholas J Quinn, Stephanie Bills, Alexander Dellabella, Sarah E Gregar, Alyssa Lear, Legacy Marsolek, Crystal Mounce, Morgan Tobin","doi":"10.1002/phar.4628","DOIUrl":"10.1002/phar.4628","url":null,"abstract":"<p><p>The objective of this scoping review was to answer the question, \"What has been published describing drug dosing in sustained low-efficiency dialysis (SLED)?\" PubMed, Embase, and Scopus were searched on November 18, 2022. Methodology followed the Arksey and O'Malley framework for scoping reviews and Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews guidelines. Two investigators independently screened abstracts and full-texts of citations identified related to drug dosing and SLED. Exclusion criteria included case reports, conference abstracts, pediatrics, treatment dialysis, and non-human subjects. A standardized data extraction sheet was used to collate and summarize data. The quality of evidence was evaluated by two investigators using the Mixed Methods Appraisal Tool. A total of 230 citations were identified for screening. Of these, 29 studies met criteria for inclusion after full-text review. Four drug groups including beta-lactam antibiotics, non-beta-lactam antibiotics, antifungals, and levetiracetam were identified. Dialysate rates, dialysis durations, and medication doses used varied widely across studies. Outcomes and pharmacokinetic parameters that were assessed were also heterogenous. Drug dosing in SLED is challenging and there is minimal evidence available to guide appropriate dosing. Larger studies are needed to more accurately determine how to appropriately dose medications in SLED. Therapeutic drug monitoring should be used in all patients on SLED when available.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"948-955"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865046","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":"Precision medicine to identify, prevent, and treat pediatric obesity.","authors":"Emma M Tillman, Selsbiel Mertami","doi":"10.1002/phar.4626","DOIUrl":"10.1002/phar.4626","url":null,"abstract":"<p><p>Pediatric obesity is a growing health concern that has many secondary adverse health implications. Personalized medicine is a tool that can be used to optimize diagnosis and treatments of many diseases. In this review, we will focus on three areas related to the genetics of pediatric obesity: (i) genetic causes predisposing to pediatric obesity, (ii) pharmacogenomics that may predict weight gain associated with pharmacotherapy, and (iii) pharmacogenomics of anti-obesity pharmacotherapy. This narrative review evaluates genetic cause of pediatric obesity and how genetic findings can be used to optimize pharmacotherapy to minimize weight gain and optimize obesity treatment in pediatric patients. Pediatric obesity has many genetic causes including genomic obesity syndromes and monogenic obesity disorders. Several genetic etiologies of obesity have current or emerging targeted genetic therapies. Pharmacogenomic (PGx) targets associated with pharmacotherapy-induced weight gain have been identified for antipsychotic, antiepileptic, antidepressant therapies, and steroids, yet to date no clinical guidelines exist for application use of PGx to tailor pharmacotherapy to avoid weight gain. As legislation evolves for genetic testing coverage and technology advances, this will decrease cost and expand access to genetic testing. This will result in identification of potential genetic causes of obesity and genes that predispose to pharmacotherapy-induced weight gain. Advances in precision medicine can ultimately lead to development of clinical practice guidelines on how to apply genetic findings to optimize pharmacotherapy to treat genetic targets of obesity and avoid weight gain as an adverse event associated with pharmacotherapy.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"939-947"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644383","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":"Aztreonam-avibactam: The dynamic duo against multidrug-resistant gram-negative pathogens.","authors":"Mohammed Al Musawa, Callan R Bleick, Shelbye R Herbin, Kaylee E Caniff, Sean R Van Helden, Michael J Rybak","doi":"10.1002/phar.4629","DOIUrl":"10.1002/phar.4629","url":null,"abstract":"<p><p>Antimicrobial resistance poses a significant public health challenge, particularly with the rise of gram-negative hospital-acquired infections resistant to carbapenems. Aztreonam-avibactam (ATM-AVI) is a promising new combination therapy designed to combat multidrug-resistant (MDR) gram-negative bacteria, including those producing metallo-β-lactamases (MBLs). Aztreonam, a monobactam antibiotic, is resistant to hydrolysis by MBLs but can be degraded by other β-lactamases. Avibactam, a novel non-β-lactam β-lactamase inhibitor, effectively neutralizes extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases, restoring aztreonam's efficacy against resistant pathogens. This review covers the chemistry, mechanisms of action, spectrum of activity, pharmacokinetics, pharmacodynamics, and clinical efficacy of ATM-AVI. ATM-AVI combination has shown efficacy against a wide range of resistant Enterobacterales and other gram-negative bacteria in both in vitro and clinical studies. Pharmacokinetic and pharmacodynamic analyses demonstrate that ATM-AVI maintains effective drug concentrations in the body, with dose adjustments recommended for patients with renal impairment. Clinical trials, including the REVISIT and ASSEMBLE studies, have demonstrated the safety and efficacy of ATM-AVI in treating complicated intra-abdominal infections (cIAI), urinary tract infections (UTIs), and hospital-acquired pneumonia (HAP) caused by MDR gram-negative pathogens. The European Medicines Agency (EMA) has approved ATM-AVI for these indications, and further research is ongoing to optimize dosing regimens and expand its clinical use. This combination represents a critical advancement in the fight against antimicrobial resistance, offering a new therapeutic option for treating severe infections caused by MDR gram-negative, including MBL-producing, bacteria.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"927-938"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731826","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":"Comment on \"The power and pitfalls of underpowered studies\".","authors":"Chia Siang Kow, Dinesh Sangarran Ramachandram, Syed Shahzad Hasan, Kaeshaelya Thiruchelvam","doi":"10.1002/phar.4624","DOIUrl":"https://doi.org/10.1002/phar.4624","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"44 12","pages":"956"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907516","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":"Pilot and feasibility study of dietary composition with elexacaftor-tezacaftor-ivacaftor concentrations in people with cystic fibrosis.","authors":"Natalie R Rose, Julianna Bailey, Justin D Anderson, Ashritha R Chalamalla, Kevin J Ryan, Edward P Acosta, Jennifer S Guimbellot","doi":"10.1002/phar.4630","DOIUrl":"10.1002/phar.4630","url":null,"abstract":"<p><strong>Background: </strong>Nutritional support for people with cystic fibrosis (PwCF) after the implementation of novel drug therapies is shifting from managing malnutrition through a high-fat, high-calorie diet to managing emerging incidences of obesity in this population. Additionally, dietary recommendations prescribed with elexacaftor/tezacaftor/ivacaftor (ETI) recommend taking this drug with a fat-containing meal, which is variably interpreted by patients. This pilot and feasibility study was conducted to assess dietary fat intake and body composition on ETI plasma concentrations.</p><p><strong>Methods: </strong>Ten participants were enrolled in a 1:1 crossover design by dietary recommendations. To mimic recommendations made during routine clinical care, participants were instructed to consume either a general healthful diet (no more than 30% calories from fat) or a high-fat diet (>40% calories from fat) for a week before crossing over to the alternative diet.</p><p><strong>Results: </strong>This pilot study was acceptable to and feasible for study participants. Most participants increased fat intake calories when following a high-fat diet. Body composition measurements showed a trending correlation between lean mass and fat-free mass with ETI plasma concentrations. ETI compounds were quantified in plasma at 0 h (prior to the ETI morning dose) and 6 h after ingestion, and consuming a high-fat diet did not significantly impact ETI concentrations.</p><p><strong>Conclusions: </strong>Consuming a higher-fat diet did not significantly impact ETI plasma concentrations, and all participants were in range for clinical effectiveness of ETI regardless of fat intake. This work provides vital pilot data to design larger studies to clarify dietary composition for optimal ETI exposure for PwCF on this therapy.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"920-926"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882581","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":"Challenges in renally eliminated medication use: Evaluating cystatin C and serum creatinine eGFR discordance.","authors":"Brandy N Hernandez, Patrick M Wieruszewski, Jason N Barreto, Kristin C Cole, Shivam Damani, Sandra L Kane-Gill, Kianoush B Kashani, Ellen Kelly, Andrew D Rule, Hilary R Teaford, Jaleh Zand, Erin F Barreto","doi":"10.1002/phar.4627","DOIUrl":"10.1002/phar.4627","url":null,"abstract":"<p><strong>Background: </strong>Accurately estimating glomerular filtration rate (GFR) is crucial for dosing medications in hospitalized patients. Due to limitations of serum creatinine for GFR estimation, serum cystatin C (CysC) has been explored as an alternative functional kidney biomarker. This study assessed discordance between eGFR_Cr and eGFR_CysC in a large sample of hospitalized patients and examined the frequency of renally eliminated medications affected by eGFR discordance.</p><p><strong>Methods: </strong>This multisite historical study included adults hospitalized between 2011 and 2023 with CysC and serum creatinine reported within 24 h of each other. The first concurrent biomarker pair for each patient was analyzed. eGFR discordance and use of renally eliminated medications were described.</p><p><strong>Results: </strong>17,718 hospitalized patients with concurrent creatinine and CysC assessments were included. The median eGFR_Cr was 65 mL/min, and the eGFR_CysC was 46 mL/min. The median absolute difference of eGFR_Cr-eGFR_CysC was 15 mL/min, and 7972 patients (45%) had a > 30% absolute difference. There was a significantly greater percentage of patients with an eGFR <30 mL/min based on eGFR_CysC (26%) compared to eGFR_Cr (15%) (p < 0.001). Patients were prescribed an average of 20 medications in the 24 h surrounding the concurrent biomarker assessment. Renally eliminated medications accounted for 39% ± 13% of medication orders, and 80% of patients with eGFR discordance were prescribed five or more renally eliminated medications.</p><p><strong>Conclusion: </strong>Substantial eGFR discordance between eGFR_CysC and eGFR_Cr was observed in hospitalized patients, which directly affects the dosing of renally eliminated medications. Further research is needed to optimize the pharmacotherapy of renally eliminated medications with discordant GFR assessments to improve medication safety and effectiveness.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"898-906"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731827","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":"Response to comment on: \"The power and pitfalls of underpowered studies\".","authors":"Ryan M Carnahan, Grant D Brown","doi":"10.1002/phar.4625","DOIUrl":"https://doi.org/10.1002/phar.4625","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"44 12","pages":"957-958"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907519","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":"External evaluation of neonatal vancomycin population pharmacokinetic models: Moving from first-order equations to Bayesian-guided therapeutic monitoring.","authors":"Mathieu Blouin, Marie-Élaine Métras, Camille Gaudreault, Marie-Hélène Dubé, Marie-Christine Boulanger, Karine Cloutier, Mehdi El Hassani, Aysenur Yaliniz, Isabelle Viel-Thériault, Amélie Marsot","doi":"10.1002/phar.4623","DOIUrl":"10.1002/phar.4623","url":null,"abstract":"<p><strong>Introduction: </strong>Guidelines for vancomycin therapeutic monitoring recommend using a Bayesian approach with a population pharmacokinetic model to estimate the 24 h area under the concentration-time curve over first-order equations. Thus, we performed an external evaluation of population pharmacokinetic models of vancomycin in neonates and compared Bayesian results with those observed in clinical practice via pharmacokinetic equations to improve therapeutic monitoring by proposing optimized initial dosing nomograms and assessing the feasibility of reduced blood sampling strategies using the most predictive models.</p><p><strong>Methods: </strong>Models were identified from the literature and evaluated via an external neonatal population. A priori predictive performance was first assessed by prediction-based diagnostics, then by simulation-based diagnostics and a posteriori analyses only if deemed satisfactory; model-informed vancomycin exposure was also compared with reference first-order pharmacokinetic equations. The best-performing models were ultimately subjected to Monte Carlo simulations to develop new initial dosing nomograms offering the highest probability of achieving therapeutic target.</p><p><strong>Results: </strong>A total of 28 population pharmacokinetic models were evaluated in the external dataset, which includes 72 neonates and 380 vancomycin concentrations. Eleven models had an adequate predictive performance with bias ≤ ± 15% and imprecision <math><mo>≤</mo></math> 30%, while the Bayesian approach yielded over 75% agreement with reference exposure values in most cases. Nonetheless, Capparelli et al. and Mehrotra et al. models performed the best overall, showing the lowest imprecisions of 16.8% and 16.9%, respectively; both models recommended higher dosage regimens than the theoretical nomogram currently applied to favor therapeutic target attainment.</p><p><strong>Discussion: </strong>We externally evaluated numerous neonatal population pharmacokinetic models of vancomycin and used the most predictive ones to advocate new initial dosing nomograms. Clinical implementation of the Bayesian approach could reduce the time needed to reach therapeutic target and limit the number of blood samples in newborns compared with traditional pharmacokinetic equations.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"907-919"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625954","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}