Pharmacotherapy最新文献

{"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}

{"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}

{"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":2.9,"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}

{"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_MAX], area under the curve [AUC], and trough [C_Trough].</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_MAX and AUC to plasma C_MAX and AUC (i.e., C_MAXmethod and AUC_method). The CSF C_Trough for each ARV was compared with in vitro literature values of HIV inhibitory concentration values (IC_{50, 90, or 95}).</p><p><strong>Results: </strong>Emtricitabine exhibited the highest median relative CSF penetration (C_MAXmethod, 46.3%; AUC_method, 72%) and dolutegravir had the lowest CSF penetration (C_MAXmethod, 0.57%; AUC_method, 0.57%). Tenofovir, lamivudine, atazanavir, and raltegravir had median estimated CSF C_Trough concentrations less than IC_{50, 90, or 95}. 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_MAX or C_Trough) 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":2.9,"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}

{"title":"Response to comment on \"Use of proton pump inhibitors and risk of severe COVID-19: A case-control study in United States Medicare beneficiaries\".","authors":"Andrew D Mosholder, Michael Wernecke, David J Graham","doi":"10.1002/phar.70003","DOIUrl":"https://doi.org/10.1002/phar.70003","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"45 4","pages":"239"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009120","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":"Comment on \"Use of proton pump inhibitors and risk of severe COVID-19: A case-control study in United States Medicare beneficiaries\".","authors":"Chia Siang Kow, Dinesh Sangarran Ramachandram, Syed Shahzad Hasan, Kaeshaelya Thiruchelvam","doi":"10.1002/phar.70002","DOIUrl":"10.1002/phar.70002","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"238"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441254","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":"GLP-1RA-induced delays in gastrointestinal motility: Predicted effects on coadministered drug absorption by PBPK analysis.","authors":"Levi Hooper, Shuhan Liu, Manjunath P Pai","doi":"10.1002/phar.70007","DOIUrl":"10.1002/phar.70007","url":null,"abstract":"<p><strong>Background: </strong>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are breakthrough medicines for obesity treatment and have rapidly gained widespread clinical application. Although GLP-1RAs are generally not associated with drug-drug interactions (DDIs) via drug metabolism or transporter pathways, their effects on reduced gastrointestinal (GI) motility could influence the pharmacokinetics of coadministered oral medications.</p><p><strong>Objectives: </strong>This study uses physiologically based pharmacokinetic (PBPK) modeling to evaluate the DDI potential of GLP-1RA-induced GI motility delays.</p><p><strong>Methods: </strong>Using Certara's Simcyp™ Simulator V23, we modeled the pharmacokinetics of atorvastatin, metformin, metoprolol, ethinyl estradiol, and digoxin in a virtual cohort of obese adults (n = 1000). GLP-1RA-related gastric emptying delays were simulated based on capsule endoscopy data from liraglutide-treated patients. Results were compared with clinical data from semaglutide and liraglutide users. Additionally, exploratory analyses were conducted on frequently coadministered drugs identified from the 2022 Medical Expenditure Panel Survey, including rosuvastatin and dabigatran.</p><p><strong>Results: </strong>GLP-1RA-induced gastric emptying delays led to increased area under the concentration-time curve (AUC) and prolonged time to maximum concentration (Tmax) for several medications. The model outputs for rosuvastatin, valsartan, and dabigatran indicate increases in AUC by 64%, 90%, and 205%, respectively. Dabigatran, a narrow therapeutic index anticoagulant, exhibited the most significant changes, raising potential concerns of higher drug exposure.</p><p><strong>Conclusions: </strong>PBPK modeling suggests that GLP-1RAs can influence the pharmacokinetics of oral medications by delaying gastric emptying, potentially leading to clinically relevant DDIs. While further clinical validation and pharmacovigilance is needed, these findings highlight the importance of PBPK tools in predicting and potentially mitigating risks associated with GLP-1RA use.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"211-219"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of antibiotic safety in pregnancy-2025 update.","authors":"Johny Nguyen, Victoria Madonia, Christopher M Bland, Kayla R Stover, Lea S Eiland, Julia Keating, Madeline Lemmon, P Brandon Bookstaver","doi":"10.1002/phar.70010","DOIUrl":"10.1002/phar.70010","url":null,"abstract":"<p><p>Antibiotics constitute the majority of prescriptions for women during pregnancy. Common bacterial infections, including urinary tract infections, skin and soft tissue infections, and upper and lower respiratory tract infections, are expected in pregnancy, similar to the general public. These infections carry additional risks to both the woman and fetus; thus, antibiotics are often prescribed. Antibiotics, like other drugs, are not benign and may carry additional risks to the fetus beyond commonly encountered adverse drug events seen across most patient populations. Since 2014, 19 new antibiotics have been approved by the United States Food and Drug Administration. Additionally, in 2018, the previously held pregnancy category rating expired, and all manufacturers' labeling was updated with new narrative language reflecting safety in pregnancy, lactation, and males and females of reproductive potential. This review provides a comprehensive summary of available data and an update to the 2015 publication regarding the safe use of antibiotics in pregnancy. The primary focus of this review is on newly approved antibiotics, along with any additional published evidence on previously reviewed antibiotics. Data on lactation or antiviral or antifungal use in pregnancy are not included. Clinicians should remain updated on current available evidence and vigilant to provide safe and effective antibiotic decision-making in pregnant women.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"227-237"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656879","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":"Prevalence of potentially inappropriately prescribed medications among older adults receiving peritoneal dialysis.","authors":"Armando Silva Almodovar, Macarius Donneyong, Eric Seiber, Milap C Nahata","doi":"10.1002/phar.70008","DOIUrl":"10.1002/phar.70008","url":null,"abstract":"<p><strong>Introduction: </strong>The prevalence of exposure to supratherapeutic doses or contraindicated medications based on renal dosing criteria, also known as potentially inappropriately prescribed medications (PIPM), is currently unknown among patients on peritoneal dialysis (PD). The primary objective of this study was to evaluate the prevalence of PIPM in the first year of PD among Medicare patients in the United States.</p><p><strong>Methods: </strong>This was a retrospective longitudinal cohort analysis of patients starting PD in 2018 in the United States Renal Data System database. Inclusion criteria were patients >65 years of age, continuously enrolled in Medicare Part D for 12 months, and prescribed ≥1 medication(s) at the start of dialysis. Prevalence of exposure to PIPM was determined at the start of dialysis and quarterly over 1 year. Logistic regression evaluated which patient characteristics (age, sex, race, Hispanic ethnicity, rurality, social deprivation index (SDI), United States region, polypharmacy, and diagnosis of diabetes and hypertension) were associated with exposure to ≥1 PIPM at the start of PD.</p><p><strong>Results: </strong>There were 3760 patients included, and 28% were exposed to PIPM at the start of dialysis, and 21.8% were still exposed by the end of the first year. Patients with ≥4 versus <4 medications were at 2.8-14.1 times the odds of being exposed to PIPM (<0.001). Other key characteristics associated with exposure to PIPM were age ≥85 versus <75 years (adjusted odds ratio [aOR] 0.67, 95% confidence interval [CI] 0.48-0.95 p = 0.03), living in the South versus the Northeast (aOR 1.30 95% CI 1.02-1.66, p = 0.04), and diagnosis of diabetes (aOR 1.52, 95% CI 1.29-1.78, p < 0.001).</p><p><strong>Conclusion: </strong>This study found that approximately 20%-30% of patients receiving PD were exposed to PIPM from 2018 to 2019. Results from this study support the need to create medication management programs to decrease exposure to PIPM.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"203-210"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543023","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":"Changes in serum potassium in people with type 2 diabetes taking sodium-glucose co-transporter-2 inhibitors.","authors":"Kellye Eagan, Charlotte Bolch, Elizabeth Van Dril, Christie Schumacher","doi":"10.1002/phar.70006","DOIUrl":"10.1002/phar.70006","url":null,"abstract":"<p><strong>Study objective: </strong>The primary objective of this study was to determine if there was a significant change in potassium levels with sodium-glucose co-transporter-2 (SGLT2) inhibitor therapy in people with type 2 diabetes (T2D). A co-primary objective was to evaluate which factors may predispose a patient to changes in potassium levels.</p><p><strong>Design: </strong>Multicenter retrospective cohort chart review.</p><p><strong>Data source: </strong>Study patients were identified through an electronic medical record-generated report if they had T2D and were prescribed an SGLT2 inhibitor from January 2013 to September 2019.</p><p><strong>Patients: </strong>Patients were included if they had T2D, were receiving care at Advocate Medical Group, and were confirmed to have taken one of the four SGLT2 inhibitors available at the time of study approval, canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin, for at least 7 days. Patients were excluded if they did not have a basic metabolic panel or comprehensive metabolic panel recorded 1 year prior to or 6 months after SGLT2 inhibitor therapy initiation.</p><p><strong>Results: </strong>Data extraction from the electronic medical record identified 6425 patients receiving an SGLT2 inhibitor, of which 1926 met inclusion criteria. The SGLT2 inhibitor most prescribed was canagliflozin (43.7%), followed by empagliflozin (36.9%) and dapagliflozin (19.4%). Concomitant baseline medications were thiazide diuretics (27.5%); angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors (72.1%); and/or mineralocorticoid receptor antagonists (27.2%). A statistically significant change in potassium levels was found with dapagliflozin (p = 0.018); albeit not clinically significant. No other statistically significant changes or patterns were identified. The overall mean change in serum potassium from baseline was 0.021 mmol/L within 3 months; 0.007 mmol/L from 3 to 5.9 months; -0.017 mmol/L within 6-12 months; and 0.004 mmol/L after more than 12 months.</p><p><strong>Conclusions: </strong>No clinically significant increase or decrease in potassium levels was observed upon initiation of SGLT2 inhibitor therapy in patients with T2D. This was consistent across background medication use and patient-specific factors. Baseline potassium should not be a factor in initiating SGLT2 inhibitor therapy, if clinically indicated, in patients with T2D.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"194-202"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483887","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}