Pharmacotherapy最新文献

{"title":"Correction of posaconazole concentrations for hypoalbuminemia.","authors":"David E Nix, Fekade Sime, Jason A Roberts","doi":"10.1002/phar.70021","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-18","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}

{"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":"https://doi.org/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":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-16","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}

{"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":"https://doi.org/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":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"https://doi.org/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":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/10.1002/phar.70017","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-09","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":"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}